1. U.S. Code
  2. title 21
  3. chapter 9
  4. subchapter V
  5. part A
  6. § 353

Collapse to view only § 353. Exemptions and consideration for certain drugs, devices, and biological products

§ 351. Adulterated drugs and devicesA drug or device shall be deemed to be adulterated—
(a) Poisonous, insanitary, etc., ingredients; adequate controls in manufacture
(1) If it consists in whole or in part of any filthy, putrid, or decomposed substance; or (2)(A) if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health; or (B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess; or (C) if it is a compounded positron emission tomography drug and the methods used in, or the facilities and controls used for, its compounding, processing, packing, or holding do not conform to or are not operated or administered in conformity with the positron emission tomography compounding standards and the official monographs of the United States Pharmacopoeia to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, that it purports or is represented to possess; or (3) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health; or (4) if (A) it bears or contains, for purposes of coloring only, a color additive which is unsafe within the meaning of section 379e(a) of this title, or (B) it is a color additive the intended use of which in or on drugs or devices is for purposes of coloring only and is unsafe within the meaning of section 379e(a) of this title; or (5) if it is a new animal drug which is unsafe within the meaning of section 360b of this title; or (6) if it is an animal feed bearing or containing a new animal drug, and such animal feed is unsafe within the meaning of section 360b of this title.
(b) Strength, quality, or purity differing from official compendium
(c) Misrepresentation of strength, etc., where drug is unrecognized in compendium
(d) Mixture with or substitution of another substance
(e) Devices not in conformity with performance standards
(1) If it is, or purports to be or is represented as, a device which is subject to a performance standard established under section 360d of this title unless such device is in all respects in conformity with such standard.
(2) If it is declared to be, purports to be, or is represented as, a device that is in conformity with any standard recognized under section 360d(c) of this title unless such device is in all respects in conformity with such standard.
(f) Certain class III devices
(1) If it is a class III device—
(A)
(i) which is required by an order issued under subsection (b) of section 360e of this title to have an approval under such section of an application for premarket approval and which is not exempt from section 360e of this title under section 360j(g) of this title, and
(ii)(I) for which an application for premarket approval or a notice of completion of a product development protocol was not filed with the Secretary within the ninety-day period beginning on the date of the issuance of such order, or(II) for which such an application was filed and approval of the application has been denied, suspended, or withdrawn, or such a notice was filed and has been declared not completed or the approval of the device under the protocol has been withdrawn;
(B)
(i) which was classified under section 360c(f) of this title into class III, which under section 360e(a) of this title is required to have in effect an approved application for premarket approval, and which is not exempt from section 360e of this title under section 360j(g) of this title, and
(ii) which has an application which has been suspended or is otherwise not in effect; or
(C) which was classified under section 360j(l) of this title into class III, which under such section is required to have in effect an approved application under section 360e of this title, and which has an application which has been suspended or is otherwise not in effect.
(2)
(A) In the case of a device classified under section 360c(f) of this title into class III and intended solely for investigational use, paragraph 1
1 So in original. Probably should be “subparagraph”.
(1)(B) shall not apply with respect to such device during the period ending on the ninetieth day after the date of the promulgation of the regulations prescribing the procedures and conditions required by section 360j(g)(2) of this title.
(B) In the case of a device subject to an order issued under subsection (b) of section 360e of this title, paragraph 1 (1) shall not apply with respect to such device during the period ending—
(i) on the last day of the thirtieth calendar month beginning after the month in which the classification of the device in class III became effective under section 360c of this title, or
(ii) on the ninetieth day after the date of the issuance of such order,
whichever occurs later.
(3) In the case of a device with respect to which a regulation was promulgated under section 360e(b) of this title prior to July 9, 2012, a reference in this subsection to an order issued under section 360e(b) of this title shall be deemed to include such regulation.
(g) Banned devices
(h) Manufacture, packing, storage, or installation of device not in conformity with applicable requirements or conditions
(i) Failure to comply with requirements under which device was exempted for investigational use
(j) Delayed, denied, or limited inspection; refusal to permit entry or inspection
(June 25, 1938, ch. 675, § 501, 52 Stat. 1049; Pub. L. 86–618, title I, § 102(b)(1), July 12, 1960, 74 Stat. 398; Pub. L. 87–781, title I, § 101, Oct. 10, 1962, 76 Stat. 780; Pub. L. 90–399, § 101(a), July 13, 1968, 82 Stat. 343; Pub. L. 94–295, §§ 3(d), 9(b)(1), May 28, 1976, 90 Stat. 576, 583; Pub. L. 101–629, § 9(b), Nov. 28, 1990, 104 Stat. 4521; Pub. L. 102–571, title I, § 107(8), Oct. 29, 1992, 106 Stat. 4499; Pub. L. 105–115, title I, § 121(b)(1), title II, § 204(c), Nov. 21, 1997, 111 Stat. 2320, 2336; Pub. L. 112–144, title VI, § 608(b)(2), title VII, §§ 707(a), 711, July 9, 2012, 126 Stat. 1058, 1068, 1071; Pub. L. 115–52, title VII, § 702(c), Aug. 18, 2017, 131 Stat. 1056.)

CITE AS: 21 USC 351

§ 352. Misbranded drugs and devicesA drug or device shall be deemed to be misbranded—
(a) False or misleading label
(1) If its labeling is false or misleading in any particular. Health care economic information provided to a payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis, carrying out its responsibilities for the selection of drugs or devices for coverage or reimbursement, shall not be considered to be false or misleading under this paragraph if the health care economic information relates to an indication approved under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 for such drug or device, is based on competent and reliable scientific evidence, and includes, where applicable, a conspicuous and prominent statement describing any material differences between the health care economic information and the labeling approved for the drug or device under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42. The requirements set forth in section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 shall not apply to health care economic information provided to such a payor, committee, or entity in accordance with this paragraph. Information that is relevant to the substantiation of the health care economic information presented pursuant to this paragraph shall be made available to the Secretary upon request.
(2)
(A) For purposes of this paragraph,1
1 So in original. The term “health care economic information” appears only in par. (1).
the term “health care economic information” means any analysis (including the clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis) that identifies, measures, or describes the economic consequences, which may be based on the separate or aggregated clinical consequences of the represented health outcomes, of the use of a drug or device. Such analysis may be comparative to the use of another drug or device, to another health care intervention, or to no intervention.
(B) Such term does not include any analysis that relates only to an indication that is not approved under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 for such drug or device.
(b) Package form; contents of label
(c) Prominence of information on label
(d) Repealed. Pub. L. 105–115, title I, § 126(b), Nov. 21, 1997, 111 Stat. 2327
(e) Designation of drugs or devices by established names
(1)
(A) If it is a drug, unless its label bears, to the exclusion of any other nonproprietary name (except the applicable systematic chemical name or the chemical formula)—
(i) the established name (as defined in subparagraph (3)) of the drug, if there is such a name;
(ii) the established name and quantity or, if determined to be appropriate by the Secretary, the proportion of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including whether active or not the established name and quantity or if determined to be appropriate by the Secretary, the proportion of any bromides, ether, chloroform, acetanilide, acetophenetidin, amidopyrine, antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury, ouabain, strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein, except that the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this subclause, shall not apply to nonprescription drugs not intended for human use; and
(iii) the established name of each inactive ingredient listed in alphabetical order on the outside container of the retail package and, if determined to be appropriate by the Secretary, on the immediate container, as prescribed in regulation promulgated by the Secretary, except that nothing in this subclause shall be deemed to require that any trade secret be divulged, and except that the requirements of this subclause with respect to alphabetical order shall apply only to nonprescription drugs that are not also cosmetics and that this subclause shall not apply to nonprescription drugs not intended for human use.
(B) For any prescription drug the established name of such drug or ingredient, as the case may be, on such label (and on any labeling on which a name for such drug or ingredient is used) shall be printed prominently and in type at least half as large as that used thereon for any proprietary name or designation for such drug or ingredient, except that to the extent that compliance with the requirements of subclause (ii) or (iii) of clause (A) or this clause is impracticable, exemptions shall be established by regulations promulgated by the Secretary.
(2) If it is a device and it has an established name, unless its label bears, to the exclusion of any other nonproprietary name, its established name (as defined in subparagraph (4)) prominently printed in type at least half as large as that used thereon for any proprietary name or designation for such device, except that to the extent compliance with the requirements of this subparagraph is impracticable, exemptions shall be established by regulations promulgated by the Secretary.
(3) As used in subparagraph (1), the term “established name”, with respect to a drug or ingredient thereof, means (A) the applicable official name designated pursuant to section 358 of this title, or (B), if there is no such name and such drug, or such ingredient, is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this subparagraph applies, then the common or usual name, if any, of such drug or of such ingredient, except that where clause (B) of this subparagraph applies to an article recognized in the United States Pharmacopeia and in the Homoeopathic Pharmacopoeia under different official titles, the official title used in the United States Pharmacopeia shall apply unless it is labeled and offered for sale as a homoeopathic drug, in which case the official title used in the Homoeopathic Pharmacopoeia shall apply.
(4) As used in subparagraph (2), the term “established name” with respect to a device means (A) the applicable official name of the device designated pursuant to section 358 of this title, (B) if there is no such name and such device is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this subparagraph applies, then any common or usual name of such device.
(f) Directions for use and warnings on label
(g) Representations as recognized drug; packing and labeling; inconsistent requirements for designation of drug
(h) Deteriorative drugs; packing and labeling
(i) Drug; misleading container; imitation; offer for sale under another name
(1) If it is a drug and its container is so made, formed, or filled as to be misleading; or (2) if it is an imitation of another drug; or (3) if it is offered for sale under the name of another drug.
(j) Health-endangering when used as prescribed
(k), (l) Repealed. Pub. L. 105–115, title I, § 125(a)(2)(B), (b)(2)(D), Nov. 21, 1997, 111 Stat. 2325
(m) Color additives; packing and labeling
(n) Prescription drug advertisements: established name; quantitative formula; side effects, contraindications, and effectiveness; prior approval; false advertising; labeling; construction of the Convention on Psychotropic Substances
(o) Drugs or devices from nonregistered establishments
(p) Packaging or labeling of drugs in violation of regulations
(q) Restricted devices using false or misleading advertising or used in violation of regulations
(r) Restricted devices not carrying requisite accompanying statements in advertisements and other descriptive printed matter
(s) Devices subject to performance standards not bearing requisite labeling
(t) Devices for which there has been a failure or refusal to give required notification or to furnish required material or information
(u) Identification of manufacturer
(1) Subject to paragraph (2), if it is a reprocessed single-use device, unless it, or an attachment thereto, prominently and conspicuously bears the name of the manufacturer of the reprocessed device, a generally recognized abbreviation of such name, or a unique and generally recognized symbol identifying such manufacturer.
(2) If the original device or an attachment thereto does not prominently and conspicuously bear the name of the manufacturer of the original device, a generally recognized abbreviation of such name, or a unique and generally recognized symbol identifying such manufacturer, a reprocessed device may satisfy the requirements of paragraph (1) through the use of a detachable label on the packaging that identifies the manufacturer and is intended to be affixed to the medical record of a patient.
(v) Reprocessed single-use devices
(w) New animal drugsIf it is a new animal drug—
(1) that is conditionally approved under section 360ccc of this title and its labeling does not conform with the approved application or section 360ccc(f) of this title, or that is not conditionally approved under section 360ccc of this title and its label bears the statement set forth in section 360ccc(f)(1)(A) of this title;
(2) that is indexed under section 360ccc–1 of this title and its labeling does not conform with the index listing under section 360ccc–1(e) of this title or 360ccc–1(h) of this title, or that has not been indexed under section 360ccc–1 of this title and its label bears the statement set forth in section 360ccc–1(h) of this title; or
(3) for which an application has been approved under section 360b of this title and the labeling of such drug does not include the application number in the format: “Approved by FDA under (A)NADA # xxx–xxx”, except that this subparagraph shall not apply to representative labeling required under section 514.1(b)(3)(v)(b) of title 21, Code of Federal Regulations (or any successor regulation) for animal feed bearing or containing a new animal drug.
(x) Nonprescription drugs
(y) Drugs subject to approved risk evaluation and mitigation strategy
(z) Postmarket studies and clinical trials; new safety information in labeling
(aa) Unpaid fees; failure to submit identifying information
(bb) False or misleading advertisement or promotion of compounded drug
(cc) Failure to bear product identifier
(dd) Improper labeling of antimicrobial drugs
(ee) Nonprescription drug subject to regulation
(ff) Drugs manufactured, prepared, propagated, compounded, or processed in facilities for which fees have not been paid
(gg) Product information prior to approval
(1) Unless its labeling bears adequate directions for use in accordance with paragraph (f), except that (in addition to drugs or devices that conform with exemptions pursuant to such paragraph) no drug or device shall be deemed to be misbranded under such paragraph through the provision of truthful and not misleading product information to a payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis carrying out its responsibilities for the selection of drugs or devices for coverage or reimbursement if the product information relates to an investigational drug or device or investigational use of a drug or device that is approved, cleared, granted marketing authorization, or licensed under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 (as applicable), provided—
(A) the product information includes—
(i) a clear statement that the investigational drug or device or investigational use of a drug or device has not been approved, cleared, granted marketing authorization, or licensed under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 (as applicable) and that the safety and effectiveness of such drug or device for such use has not been established;
(ii) information related to the stage of development of the drug or device involved, such as—(I) the status of any study or studies in which the investigational drug or device or investigational use is being investigated;(II) how the study or studies relate to the overall plan for the development of the drug or device; and(III) whether an application, premarket notification, or request for classification for the investigational drug or device or investigational use has been submitted to the Secretary and when such a submission is planned;
(iii) in the case of information that includes factual presentations of results from studies, which shall not be selectively presented, a description of—(I) all material aspects of study design, methodology, and results; and(II) all material limitations related to the study design, methodology, and results;
(iv) where applicable, a prominent statement disclosing the indication or indications for which the Secretary has approved, granted marketing authorization, cleared, or licensed the product pursuant to section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42, and a copy of the most current required labeling; and
(v) updated information, if previously communicated information becomes materially outdated as a result of significant changes or as a result of new information regarding the product or its review status; and
(B) the product information does not include—
(i) information that represents that an unapproved product—(I) has been approved, cleared, granted marketing authorization, or licensed under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 (as applicable); or(II) has otherwise been determined to be safe or effective for the purpose or purposes for which the drug or device is being studied; or
(ii) information that represents that an unapproved use of a drug or device that has been so approved, granted marketing authorization, cleared, or licensed—(I) is so approved, granted marketing authorization, cleared, or licensed; or(II) that the product is safe or effective for the use or uses for which the drug or device is being studied.
(2) For purposes of this paragraph, the term “product information” includes—
(A) information describing the drug or device (such as drug class, device description, and features);
(B) information about the indication or indications being investigated;
(C) the anticipated timeline for a possible approval, clearance, marketing authorization, or licensure pursuant to section 355, 360(k), 360c, or 360e of this title or section 262 of title 42;
(D) drug or device pricing information;
(E) patient utilization projections;
(F) product-related programs or services; and
(G) factual presentations of results from studies that do not characterize or make conclusions regarding safety or efficacy.
(June 25, 1938, ch. 675, § 502, 52 Stat. 1050; June 23, 1939, ch. 242, § 3, 53 Stat. 854; Dec. 22, 1941, ch. 613, § 2, 55 Stat. 851; July 6, 1945, ch. 281, § 2, 59 Stat. 463; Mar. 10, 1947, ch. 16, § 2, 61 Stat. 11; July 13, 1949, ch. 305, § 1, 63 Stat. 409; Aug. 5, 1953, ch. 334, § 1, 67 Stat. 389; Pub. L. 86–618, title I, § 102(b)(2), July 12, 1960, 74 Stat. 398; Pub. L. 87–781, title I, §§ 105(c), 112(a), (b), 131(a), title III, § 305, Oct. 10, 1962, 76 Stat. 785, 790, 791, 795; Pub. L. 90–399, § 105(a), July 13, 1968, 82 Stat. 352; Pub. L. 91–601, § 6(d), formerly § 7(d), Dec. 30, 1970, 84 Stat. 1673, renumbered Pub. L. 97–35, title XII, § 1205(c), Aug. 13, 1981, 95 Stat. 716; Pub. L. 94–295, §§ 3(e), 4(b)(2), 5(a), 9(b)(2), May 28, 1976, 90 Stat. 577, 580, 583; Pub. L. 95–633, title I, § 111, Nov. 10, 1978, 92 Stat. 3773; Pub. L. 102–300, § 3(a)(2), June 16, 1992, 106 Stat. 239; Pub. L. 102–571, title I, § 107(9), Oct. 29, 1992, 106 Stat. 4499; Pub. L. 103–80, § 3(m), Aug. 13, 1993, 107 Stat. 777; Pub. L. 105–115, title I, §§ 114(a), 125(a)(2)(B), (b)(2)(D), 126(b), title IV, § 412(c), Nov. 21, 1997, 111 Stat. 2312, 2325, 2327, 2375; Pub. L. 107–250, title II, § 206, title III, §§ 301(a), 302(a)(1), Oct. 26, 2002, 116 Stat. 1613, 1616; Pub. L. 108–214, § 2(b)(2)(B), Apr. 1, 2004, 118 Stat. 575; Pub. L. 108–282, title I, § 102(b)(5)(E), Aug. 2, 2004, 118 Stat. 902; Pub. L. 109–43, § 2(c)(1), Aug. 1, 2005, 119 Stat. 441; Pub. L. 109–462, § 2(d), Dec. 22, 2006, 120 Stat. 3472; Pub. L. 110–85, title IX, §§ 901(d)(3)(A), (6), 902(a), 906(a), Sept. 27, 2007, 121 Stat. 940, 942, 943, 949; Pub. L. 112–144, title III, § 306, title VII, §§ 702(a), 714(c), July 9, 2012, 126 Stat. 1024, 1065, 1074; Pub. L. 112–193, § 2(a), Oct. 5, 2012, 126 Stat. 1443; Pub. L. 113–54, title I, § 103(b), title II, § 206(b), Nov. 27, 2013, 127 Stat. 597, 639; Pub. L. 114–255, div. A, title III, §§ 3037, 3044(b)(2), Dec. 13, 2016, 130 Stat. 1105, 1121; Pub. L. 115–234, title III, § 303(a), Aug. 14, 2018, 132 Stat. 2436; Pub. L. 116–136, div. A, title III, § 3852, Mar. 27, 2020, 134 Stat. 454; Pub. L. 117–328, div. FF, title III, § 3630(a), Dec. 29, 2022, 136 Stat. 5893.)

CITE AS: 21 USC 352

§ 353. Exemptions and consideration for certain drugs, devices, and biological products
(a) Regulations for goods to be processed, labeled, or repacked elsewhere
(b) Prescription by physician; exemption from labeling and prescription requirements; misbranded drugs; compliance with narcotic and marihuana laws
(1) A drug intended for use by man which—
(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or
(B) is limited by an approved application under section 355 of this title to use under the professional supervision of a practitioner licensed by law to administer such drug;
shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.
(2) Any drug dispensed by filling or refilling a written or oral prescription of a practitioner licensed by law to administer such drug shall be exempt from the requirements of section 352 of this title, except paragraphs (a), (i)(2) and (3), (k), and (l), and the packaging requirements of paragraphs (g), (h), and (p), if the drug bears a label containing the name and address of the dispenser, the serial number and date of the prescription or of its filling, the name of the prescriber, and, if stated in the prescription, the name of the patient, and the directions for use and cautionary statements, if any, contained in such prescription. This exemption shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail, or to a drug dispensed in violation of paragraph (1) of this subsection.
(3) The Secretary may by regulation remove drugs subject to section 355 of this title from the requirements of paragraph (1) of this subsection when such requirements are not necessary for the protection of the public health.
(4)
(A) A drug that is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing the label of the drug fails to bear, at a minimum, the symbol “Rx only”.
(B) A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing the label of the drug bears the symbol described in subparagraph (A).
(5) Nothing in this subsection shall be construed to relieve any person from any requirement prescribed by or under authority of law with respect to drugs now included or which may hereafter be included within the classifications stated in sections 4721, 6001, and 6151 of title 26, or to marihuana as defined in section 4761 of title 26.
(c) Sales restrictions
(1) No person may sell, purchase, or trade or offer to sell, purchase, or trade any drug sample. For purposes of this paragraph and subsection (d), the term “drug sample” means a unit of a drug, subject to subsection (b), which is not intended to be sold and is intended to promote the sale of the drug. Nothing in this paragraph shall subject an officer or executive of a drug manufacturer or distributor to criminal liability solely because of a sale, purchase, trade, or offer to sell, purchase, or trade in violation of this paragraph by other employees of the manufacturer or distributor.
(2) No person may sell, purchase, or trade, offer to sell, purchase, or trade, or counterfeit any coupon. For purposes of this paragraph, the term “coupon” means a form which may be redeemed, at no cost or at a reduced cost, for a drug which is prescribed in accordance with subsection (b).
(3)
(A) No person may sell, purchase, or trade, or offer to sell, purchase, or trade, any drug—
(i) which is subject to subsection (b), and
(ii)(I) which was purchased by a public or private hospital or other health care entity, or(II) which was donated or supplied at a reduced price to a charitable organization described in section 501(c)(3) of title 26.
(B) Subparagraph (A) does not apply to—
(i) the purchase or other acquisition by a hospital or other health care entity which is a member of a group purchasing organization of a drug for its own use from the group purchasing organization or from other hospitals or health care entities which are members of such organization,
(ii) the sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug by an organization described in subparagraph (A)(ii)(II) to a nonprofit affiliate of the organization to the extent otherwise permitted by law,
(iii) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug among hospitals or other health care entities which are under common control,
(iv) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug for emergency medical reasons, or
(v) a sale, purchase, or trade of a drug, an offer to sell, purchase, or trade a drug, or the dispensing of a drug pursuant to a prescription executed in accordance with subsection (b).
For purposes of this paragraph, the term “entity” does not include a wholesale distributor of drugs or a retail pharmacy licensed under State law and the term “emergency medical reasons” includes transfers of a drug between health care entities or from a health care entity to a retail pharmacy undertaken to alleviate temporary shortages of the drug arising from delays in or interruptions of regular distribution schedules.
(d) Distribution of drug samples
(1) Except as provided in paragraphs (2) and (3), no person may distribute any drug sample. For purposes of this subsection, the term “distribute” does not include the providing of a drug sample to a patient by a—
(A) practitioner licensed to prescribe such drug,
(B) health care professional acting at the direction and under the supervision of such a practitioner, or
(C) pharmacy of a hospital or of another health care entity that is acting at the direction of such a practitioner and that received such sample pursuant to paragraph (2) or (3).
(2)
(A) The manufacturer or authorized distributor of record of a drug subject to subsection (b) may, in accordance with this paragraph, distribute drug samples by mail or common carrier to practitioners licensed to prescribe such drugs or, at the request of a licensed practitioner, to pharmacies of hospitals or other health care entities. Such a distribution of drug samples may only be made—
(i) in response to a written request for drug samples made on a form which meets the requirements of subparagraph (B), and
(ii) under a system which requires the recipient of the drug sample to execute a written receipt for the drug sample upon its delivery and the return of the receipt to the manufacturer or authorized distributor of record.
(B) A written request for a drug sample required by subparagraph (A)(i) shall contain—
(i) the name, address, professional designation, and signature of the practitioner making the request,
(ii) the identity of the drug sample requested and the quantity requested,
(iii) the name of the manufacturer of the drug sample requested, and
(iv) the date of the request.
(C) Each drug manufacturer or authorized distributor of record which makes distributions by mail or common carrier under this paragraph shall maintain, for a period of 3 years, the request forms submitted for such distributions and the receipts submitted for such distributions and shall maintain a record of distributions of drug samples which identifies the drugs distributed and the recipients of the distributions. Forms, receipts, and records required to be maintained under this subparagraph shall be made available by the drug manufacturer or authorized distributor of record to Federal and State officials engaged in the regulation of drugs and in the enforcement of laws applicable to drugs.
(3) The manufacturer or authorized distributor of record of a drug subject to subsection (b) may, by means other than mail or common carrier, distribute drug samples only if the manufacturer or authorized distributor of record makes the distributions in accordance with subparagraph (A) and carries out the activities described in subparagraphs (B) through (F) as follows:
(A) Drug samples may only be distributed—
(i) to practitioners licensed to prescribe such drugs if they make a written request for the drug samples, or
(ii) at the written request of such a licensed practitioner, to pharmacies of hospitals or other health care entities.
A written request for drug samples shall be made on a form which contains the practitioner’s name, address, and professional designation, the identity of the drug sample requested, the quantity of drug samples requested, the name of the manufacturer or authorized distributor of record of the drug sample, the date of the request and signature of the practitioner making the request.
(B) Drug manufacturers or authorized distributors of record shall store drug samples under conditions that will maintain their stability, integrity, and effectiveness and will assure that the drug samples will be free of contamination, deterioration, and adulteration.
(C) Drug manufacturers or authorized distributors of record shall conduct, at least annually, a complete and accurate inventory of all drug samples in the possession of representatives of the manufacturer or authorized distributor of record. Drug manufacturers or authorized distributors of record shall maintain lists of the names and address of each of their representatives who distribute drug samples and of the sites where drug samples are stored. Drug manufacturers or authorized distributors of record shall maintain records for at least 3 years of all drug samples distributed, destroyed, or returned to the manufacturer or authorized distributor of record, of all inventories maintained under this subparagraph, of all thefts or significant losses of drug samples, and of all requests made under subparagraph (A) for drug samples. Records and lists maintained under this subparagraph shall be made available by the drug manufacturer or authorized distributor of record to the Secretary upon request.
(D) Drug manufacturers or authorized distributors of record shall notify the Secretary of any significant loss of drug samples and any known theft of drug samples.
(E) Drug manufacturers or authorized distributors of record shall report to the Secretary any conviction of their representatives for violations of subsection (c)(1) or a State law because of the sale, purchase, or trade of a drug sample or the offer to sell, purchase, or trade a drug sample.
(F) Drug manufacturers or authorized distributors of record shall provide to the Secretary the name and telephone number of the individual responsible for responding to a request for information respecting drug samples.
(4) In this subsection, the term “authorized distributors of record” means those distributors with whom a manufacturer has established an ongoing relationship to distribute such manufacturer’s products.
(e) Licensing and reporting requirements for wholesale distributors; fees; definitions
(1)Requirement.—Subject to section 360eee–2 of this title:
(A)In general.—No person may engage in wholesale distribution of a drug subject to subsection (b)(1) in any State unless such person—
(i)(I) is licensed by the State from which the drug is distributed; or(II) if the State from which the drug is distributed has not established a licensure requirement, is licensed by the Secretary; and
(ii) if the drug is distributed interstate, is licensed by the State into which the drug is distributed if the State into which the drug is distributed requires the licensure of a person that distributes drugs into the State.
(B)Standards.—Each Federal and State license described in subparagraph (A) shall meet the standards, terms, and conditions established by the Secretary under section 360eee–2 of this title.
(2)Reporting and database.—
(A)Reporting.—Beginning January 1, 2015, any person who owns or operates an establishment that engages in wholesale distribution shall—
(i) report to the Secretary, on an annual basis pursuant to a schedule determined by the Secretary—(I) each State by which the person is licensed and the appropriate identification number of each such license; and(II) the name, address, and contact information of each facility at which, and all trade names under which, the person conducts business; and
(ii) report to the Secretary within a reasonable period of time and in a reasonable manner, as determined by the Secretary, any significant disciplinary actions, such as the revocation or suspension of a wholesale distributor license, taken by a State or the Federal Government during the reporting period against the wholesale distributor.
(B)Database.—Not later than January 1, 2015, the Secretary shall establish a database of authorized wholesale distributors. Such database shall—
(i) identify each authorized wholesale distributor by name, contact information, and each State where such wholesale distributor is appropriately licensed to engage in wholesale distribution;
(ii) be available to the public on the Internet Web site of the Food and Drug Administration; and
(iii) be regularly updated on a schedule determined by the Secretary.
(C)Coordination.—The Secretary shall establish a format and procedure for appropriate State officials to access the information provided pursuant to subparagraph (A) in a prompt and secure manner.
(D)Confidentiality.—Nothing in this paragraph shall be construed as authorizing the Secretary to disclose any information that is a trade secret or confidential information subject to section 552(b)(4) of title 5 or section 1905 of title 18.
(3)Costs.—
(A)Authorized fees of secretary.—If a State does not establish a licensing program for persons engaged in the wholesale distribution of a drug subject to subsection (b), the Secretary shall license a person engaged in wholesale distribution located in such State and may collect a reasonable fee in such amount necessary to reimburse the Secretary for costs associated with establishing and administering the licensure program and conducting periodic inspections under this section. The Secretary shall adjust fee rates as needed on an annual basis to generate only the amount of revenue needed to perform this service. Fees authorized under this paragraph shall be collected and available for obligation only to the extent and in the amount provided in advance in appropriations Acts. Such fees are authorized to remain available until expended. Such sums as may be necessary may be transferred from the Food and Drug Administration salaries and expenses appropriation account without fiscal year limitation to such appropriation account for salaries and expenses with such fiscal year limitation.
(B)State licensing fees.—Nothing in this chapter shall prohibit States from collecting fees from wholesale distributors in connection with State licensing of such distributors.
(4) For the purposes of this subsection and subsection (d), the term “wholesale distribution” means the distribution of a drug subject to subsection (b) to a person other than a consumer or patient, or receipt of a drug subject to subsection (b) by a person other than the consumer or patient, but does not include—
(A) intracompany distribution of any drug between members of an affiliate or within a manufacturer;
(B) the distribution of a drug, or an offer to distribute a drug among hospitals or other health care entities which are under common control;
(C) the distribution of a drug or an offer to distribute a drug for emergency medical reasons, including a public health emergency declaration pursuant to section 319 of the Public Health Service Act [42 U.S.C. 247d], except that, for purposes of this paragraph, a drug shortage not caused by a public health emergency shall not constitute an emergency medical reason;
(D) the dispensing of a drug pursuant to a prescription executed in accordance with subsection (b)(1);
(E) the distribution of minimal quantities of drug by a licensed retail pharmacy to a licensed practitioner for office use;
(F) the distribution of a drug or an offer to distribute a drug by a charitable organization to a nonprofit affiliate of the organization to the extent otherwise permitted by law;
(G) the purchase or other acquisition by a dispenser, hospital, or other health care entity of a drug for use by such dispenser, hospital, or other health care entity;
(H) the distribution of a drug by the manufacturer of such drug;
(I) the receipt or transfer of a drug by an authorized third-party logistics provider provided that such third-party logistics provider does not take ownership of the drug;
(J) a common carrier that transports a drug, provided that the common carrier does not take ownership of the drug;
(K) the distribution of a drug, or an offer to distribute a drug by an authorized repackager that has taken ownership or possession of the drug and repacks it in accordance with section 360eee–1(e) of this title;
(L) salable drug returns when conducted by a dispenser;
(M) the distribution of a collection of finished medical devices, which may include a product or biological product, assembled in kit form strictly for the convenience of the purchaser or user (referred to in this subparagraph as a “medical convenience kit”) if—
(i) the medical convenience kit is assembled in an establishment that is registered with the Food and Drug Administration as a device manufacturer in accordance with section 360(b)(2) of this title;
(ii) the medical convenience kit does not contain a controlled substance that appears in a schedule contained in the Comprehensive Drug Abuse Prevention and Control Act of 1970 [21 U.S.C. 801 et seq.];
(iii) in the case of a medical convenience kit that includes a product, the person that manufacturers the kit—(I) purchased such product directly from the pharmaceutical manufacturer or from a wholesale distributor that purchased the product directly from the pharmaceutical manufacturer; and(II) does not alter the primary container or label of the product as purchased from the manufacturer or wholesale distributor; and
(iv) in the case of a medical convenience kit that includes a product, the product is—(I) an intravenous solution intended for the replenishment of fluids and electrolytes;(II) a product intended to maintain the equilibrium of water and minerals in the body;(III) a product intended for irrigation or reconstitution;(IV) an anesthetic;(V) an anticoagulant;(VI) a vasopressor; or(VII) a sympathomimetic;
(N) the distribution of an intravenous drug that, by its formulation, is intended for the replenishment of fluids and electrolytes (such as sodium, chloride, and potassium) or calories (such as dextrose and amino acids);
(O) the distribution of an intravenous drug used to maintain the equilibrium of water and minerals in the body, such as dialysis solutions;
(P) the distribution of a drug that is intended for irrigation, or sterile water, whether intended for such purposes or for injection;
(Q) the distribution of medical gas, as defined in section 360ddd of this title;
(R) facilitating the distribution of a product by providing solely administrative services, including processing of orders and payments; or
(S) the transfer of a product by a hospital or other health care entity, or by a wholesale distributor or manufacturer operating at the direction of the hospital or other health care entity, to a repackager described in section 360eee(16)(B) of this title and registered under section 360 of this title for the purpose of repackaging the drug for use by that hospital, or other health care entity and other health care entities that are under common control, if ownership of the drug remains with the hospital or other health care entity at all times.
(5)Third-party logistics providers.—Notwithstanding paragraphs (1) through (4), each entity that meets the definition of a third-party logistics provider under section 360eee(22) of this title shall obtain a license as a third-party logistics provider as described in section 360eee–3(a) of this title and is not required to obtain a license as a wholesale distributor if the entity never assumes an ownership interest in the product it handles.
(6)Affiliate.—For purposes of this subsection, the term “affiliate” means a business entity that has a relationship with a second business entity if, directly or indirectly—
(A) one business entity controls, or has the power to control, the other business entity; or
(B) a third party controls, or has the power to control, both of the business entities.
(f) Veterinary prescription drugs
(1)
(A) A drug intended for use by animals other than man, other than a veterinary feed directive drug intended for use in animal feed or an animal feed bearing or containing a veterinary feed directive drug, which—
(i) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary for its use, is not safe for animal use except under the professional supervision of a licensed veterinarian, or
(ii) is limited by an approved application under subsection (b) of section 360b of this title, a conditionally-approved application under section 360ccc of this title, or an index listing under section 360ccc–1 of this title to use under the professional supervision of a licensed veterinarian,
shall be dispensed only by or upon the lawful written or oral order of a licensed veterinarian in the course of the veterinarian’s professional practice.
(B) For purposes of subparagraph (A), an order is lawful if the order—
(i) is a prescription or other order authorized by law,
(ii) is, if an oral order, promptly reduced to writing by the person lawfully filling the order, and filed by that person, and
(iii) is refilled only if authorized in the original order or in a subsequent oral order promptly reduced to writing by the person lawfully filling the order, and filed by that person.
(C) The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.
(2) Any drug when dispensed in accordance with paragraph (1) of this subsection—
(A) shall be exempt from the requirements of section 352 of this title, except subsections (a), (g), (h), (i)(2), (i)(3), and (p) of such section, and
(B) shall be exempt from the packaging requirements of subsections (g), (h), and (p) of such section, if—
(i) when dispensed by a licensed veterinarian, the drug bears a label containing the name and address of the practitioner and any directions for use and cautionary statements specified by the practitioner, or
(ii) when dispensed by filling the lawful order of a licensed veterinarian, the drug bears a label containing the name and address of the dispenser, the serial number and date of the order or of its filling, the name of the licensed veterinarian, and the directions for use and cautionary statements, if any, contained in such order.
The preceding sentence shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail.
(3) The Secretary may by regulation exempt drugs for animals other than man subject to section 360b, 360ccc, or 360ccc–1 of this title from the requirements of paragraph (1) when such requirements are not necessary for the protection of the public health.
(4) A drug which is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing its label fails to bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.”. A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing its label bears the statement specified in the preceding sentence.
(g) Regulation of combination products
(1)
(A) The Secretary shall, in accordance with this subsection, assign a primary agency center to regulate products that constitute a combination of a drug, device, or biological product.
(B) The Secretary shall conduct the premarket review of any combination product under a single application, whenever appropriate.
(C) For purposes of this subsection, the term “primary mode of action” means the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.
(D) The Secretary shall determine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of—
(i) a drug (other than a biological product), the agency center charged with premarket review of drugs shall have primary jurisdiction;
(ii) a device, the agency center charged with premarket review of devices shall have primary jurisdiction; or
(iii) a biological product, the agency center charged with premarket review of biological products shall have primary jurisdiction.
(E) In determining the primary mode of action of a combination product, the Secretary shall not determine that the primary mode of action is that of a drug or biological product solely because the combination product has any chemical action within or on the human body.
(F) If a sponsor of a combination product disagrees with the determination under subparagraph (D)—
(i) such sponsor may request, and the Secretary shall provide, a substantive rationale to such sponsor that references scientific evidence provided by the sponsor and any other scientific evidence relied upon by the Secretary to support such determination; and
(ii)(I) the sponsor of the combination product may propose one or more studies (which may be nonclinical, clinical, or both) to establish the relevance, if any, of the chemical action in achieving the primary mode of action of such product;(II) if the sponsor proposes any such studies, the Secretary and the sponsor of such product shall collaborate and seek to reach agreement, within a reasonable time of such proposal, not to exceed 90 calendar days, on the design of such studies; and(III) if an agreement is reached under subclause (II) and the sponsor conducts one or more of such studies, the Secretary shall consider the data resulting from any such study when reevaluating the determination of the primary mode of action of such product, and unless and until such reevaluation has occurred and the Secretary issues a new determination, the determination of the Secretary under subparagraph (D) shall remain in effect.
(2)
(A)1
1 So in original. No subpar. (B) has been enacted.
 (i) To establish clarity and certainty for the sponsor, the sponsor of a combination product may request a meeting on such combination product. If the Secretary concludes that a determination of the primary mode of action pursuant to paragraph (1)(D) is necessary, the sponsor may request such meeting only after the Secretary makes such determination. If the sponsor submits a written meeting request, the Secretary shall, not later than 75 calendar days after receiving such request, meet with the sponsor of such combination product.
(ii) A meeting under clause (i) may—(I) address the standards and requirements for market approval or clearance of the combination product;(II) address other issues relevant to such combination product, such as requirements related to postmarket modification of such combination product and good manufacturing practices applicable to such combination product; and(III) identify elements under subclauses (I) and (II) that may be more appropriate for discussion and agreement with the Secretary at a later date given that scientific or other information is not available, or agreement is otherwise not feasible regarding such elements, at the time a request for such meeting is made.
(iii) Any agreement under this subparagraph shall be in writing and made part of the administrative record by the Secretary.
(iv) Any such agreement shall remain in effect, except—(I) upon the written agreement of the Secretary and the sponsor or applicant; or(II) pursuant to a decision by the director of the reviewing division of the primary agency center, or a person more senior than such director, in consultation with consulting centers and the Office, as appropriate, that an issue essential to determining whether the standard for market clearance or other applicable standard under this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.] applicable to the combination product has been identified since the agreement was reached, or that deviating from the agreement is otherwise justifiable based on scientific evidence, for public health reasons.
(3) For purposes of conducting the premarket review of a combination product that contains an approved constituent part described in paragraph (4), the Secretary may require that the sponsor of such combination product submit to the Secretary only data or information that the Secretary determines is necessary to meet the standard for clearance or approval, as applicable, under this chapter or the Public Health Service Act, including any incremental risks and benefits posed by such combination product, using a risk-based approach and taking into account any prior finding of safety and effectiveness or substantial equivalence for the approved constituent part relied upon by the applicant in accordance with paragraph (5).
(4) For purposes of paragraph (3), an approved constituent part is—
(A) a drug constituent part of a combination product being reviewed in a single application or request under section 360e, 360(k), or 360c(f)(2) of this title (submitted in accordance with paragraph (5)), that is an approved drug, provided such application or request complies with paragraph (5);
(B) a device constituent part approved under section 360e of this title that is referenced by the sponsor and that is available for use by the Secretary under section 360j(h)(4) of this title; or
(C) any constituent part that was previously approved, cleared, or classified under section 355, 360(k), 360c(f)(2), or 360e of this title for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 379aa(a)(2) of this title.
(5)
(A) If an application is submitted under section 360e or 360(k) of this title or a request is submitted under section 360c(f)(2) of this title, consistent with any determination made under paragraph (1)(D), for a combination product containing as a constituent part an approved drug—
(i) the application or request shall include the certification or statement described in section 355(b)(2) of this title; and
(ii) the applicant or requester shall provide notice as described in section 355(b)(3) of this title.
(B) For purposes of this paragraph and paragraph (4), the term “approved drug” means an active ingredient—
(i) that was in an application previously approved under section 355(c) of this title;
(ii) where such application is relied upon by the applicant submitting the application or request described in subparagraph (A);
(iii) for which full reports of investigations that have been made to show whether such drug is safe for use and whether such drug is effective in use were not conducted by or for the applicant submitting the application or request described in subparagraph (A); and
(iv) for which the applicant submitting the application or request described in subparagraph (A) has not obtained a right of reference or use from the person by or for whom the investigations described in clause (iii) were conducted.
(C) The following provisions shall apply with respect to an application or request described in subparagraph (A) to the same extent and in the same manner as if such application or request were an application described in section 355(b)(2) of this title that referenced the approved drug:
(i) Subparagraphs (A), (B), (C), and (D) of section 355(c)(3) of this title.
(ii) Clauses (ii), (iii), and (iv) of section 355(c)(3)(E) of this title.
(iii) Subsections (b) and (c) of section 355a of this title.
(iv)Section 355f(a) of this title.
(v)Section 360cc(a) of this title.
(D) Notwithstanding any other provision of this subsection, an application or request for classification for a combination product described in subparagraph (A) shall be considered an application submitted under section 355(b)(2) of this title for purposes of section 271(e)(2)(A) of title 35.
(6) Nothing in this subsection shall be construed as prohibiting a sponsor from submitting separate applications for the constituent parts of a combination product, unless the Secretary determines that a single application is necessary.
(7) Nothing in this subsection shall prevent the Secretary from using any agency resources of the Food and Drug Administration necessary to ensure adequate review of the safety, effectiveness, or substantial equivalence of an article.
(8)
(A) Not later than 60 days after October 26, 2002, the Secretary shall establish within the Office of the Commissioner of Food and Drugs an office to ensure the prompt assignment of combination products to agency centers, the timely and effective premarket review of such products, and consistent and appropriate postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law. Additionally, the office shall, in determining whether a product is to be designated a combination product, consult with the component within the Office of the Commissioner of Food and Drugs that is responsible for such determinations. Such office (referred to in this paragraph as the “Office”) shall have appropriate scientific and medical expertise, and shall be headed by a director.
(B) In carrying out this subsection, the Office shall, for each combination product, promptly assign an agency center with primary jurisdiction in accordance with paragraph (1) for the premarket review of such product.
(C)
(i) In carrying out this subsection, the Office shall help to ensure timely and effective premarket review that involves more than one agency center by coordinating such reviews, overseeing the timeliness of such reviews, and overseeing the alignment of feedback regarding such reviews.
(ii) In order to ensure the timeliness and alignment of the premarket review of a combination product, the agency center with primary jurisdiction for the product, and the consulting agency center, shall be responsible to the Office with respect to the timeliness and alignment of the premarket review.
(iii) The Office shall ensure that, with respect to a combination product, a designated person or persons in the primary agency center is the primary point or points of contact for the sponsor of such combination product. The Office shall also coordinate communications to and from any consulting center involved in such premarket review, if requested by such primary agency center or any such consulting center. Agency communications and commitments, to the extent consistent with other provisions of law and the requirements of all affected agency centers, from the primary agency center shall be considered as communication from the Secretary on behalf of all agency centers involved in the review.
(iv) The Office shall, with respect to the premarket review of a combination product—(I) ensure that any meeting between the Secretary and the sponsor of such product is attended by each agency center involved in the review, as appropriate;(II) ensure that each consulting agency center has completed its premarket review and provided the results of such review to the primary agency center in a timely manner; and(III) ensure that each consulting center follows the guidance described in clause (vi) and advises, as appropriate, on other relevant regulations, guidances, and policies.
(v) In seeking agency action with respect to a combination product, the sponsor of such product—(I) shall identify the product as a combination product; and(II) may request in writing the participation of representatives of the Office in meetings related to such combination product, or to have the Office otherwise engage on such regulatory matters concerning the combination product.
(vi) Not later than 4 years after December 13, 2016, and after a public comment period of not less than 60 calendar days, the Secretary shall issue a final guidance that describes—(I) the structured process for managing pre-submission interactions with sponsors developing combination products;(II) the best practices for ensuring that the feedback in such pre-submission interactions represents the Agency’s best advice based on the information provided during such pre-submission interactions; 2
2 So in original. The word “and” probably should appear.
(III) the information that is required to be submitted with a meeting request under paragraph (2), how such meetings relate to other types of meetings in the Food and Drug Administration, and the form and span of any agreement reached through a meeting under such paragraph (2); 3
3 So in original. The semicolon probably should be a period.
(D) In carrying out this subsection, the Office shall ensure the consistency and appropriateness of postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law.
(E)
(i) Any dispute regarding the timeliness of the premarket review of a combination product may be presented to the Office for resolution, unless the dispute is clearly premature.
(ii) During the review process, any dispute regarding the substance of the premarket review may be presented to the Commissioner of Food and Drugs after first being considered by the agency center with primary jurisdiction of the premarket review, under the scientific dispute resolution procedures for such center. The Commissioner of Food and Drugs shall consult with the Director of the Office in resolving the substantive dispute.
(F) The Secretary, acting through the Office, shall review each agreement, guidance, or practice of the Secretary that is specific to the assignment of combination products to agency centers and shall determine whether the agreement, guidance, or practice is consistent with the requirements of this subsection. In carrying out such review, the Secretary shall consult with stakeholders and the directors of the agency centers. After such consultation, the Secretary shall determine whether to continue in effect, modify, revise, or eliminate such agreement, guidance, or practice, and shall publish in the Federal Register a notice of the availability of such modified or revised agreement, guidance or practice. Nothing in this paragraph shall be construed as preventing the Secretary from following each agreement, guidance, or practice until continued, modified, revised, or eliminated.
(G) Not later than one year after October 26, 2002 (except with respect to clause (iv), beginning not later than one year after December 13, 2016), and annually thereafter, the Secretary shall report to the appropriate committees of Congress on the activities and impact of the Office. The report shall include provisions—
(i) describing the numbers and types of combination products under review and the timeliness in days of such assignments, reviews, and dispute resolutions;
(ii) identifying the number of premarket reviews of such products that involved a consulting agency center;
(iii) describing improvements in the consistency of postmarket regulation of combination products; and
(iv) identifying the percentage of combination products for which a dispute resolution, with respect to premarket review, was requested by the combination product’s sponsor.
(H) Nothing in this paragraph shall be construed to limit the regulatory authority of any agency center.
(9) As used in this subsection:
(A) The term “agency center” means a center or alternative organizational component of the Food and Drug Administration.
(B) The term “biological product” has the meaning given the term in section 351(i) of the Public Health Service Act (42 U.S.C. 262(i)).
(C) The term “market clearance” includes—
(i) approval of an application under section 355, 357,4
4 See References in Text note below.
360e, or 360j(g) of this title;
(ii) a finding of substantial equivalence under this part;
(iii) approval of a biologics license application under subsection (a) of section 351 of the Public Health Service Act (42 U.S.C. 262); and
(iv) de novo classification under section 360c(a)(1) of this title.
(D) The terms “premarket review” and “reviews” include all activities of the Food and Drug Administration conducted prior to approval or clearance of an application, notification, or request for classification submitted under section 355, 360(k), 360c(f)(2), 360e, or 360j of this title or under section 351 of the Public Health Service Act [42 U.S.C. 262], including with respect to investigational use of the product.
(h) Regulation of certain products as drugs
(1) Any contrast agent, radioactive drug, or OTC monograph drug shall be deemed to be a drug under section 321(g) of this title and not a device under section 321(h) of this title.
(2) For purposes of this subsection:
(A) The term “contrast agent” means an article that is intended for use in conjunction with a medical imaging device, and—
(i) is a diagnostic radiopharmaceutical, as defined in sections 315.2 and 601.31 of title 21, Code of Federal Regulations (or any successor regulations); or
(ii) is a diagnostic agent that improves the visualization of structure or function within the body by increasing the relative difference in signal intensity within the target tissue, structure, or fluid.
(B) The term “radioactive drug” has the meaning given such term in section 310.3(n) of title 21, Code of Federal Regulations (or any successor regulations), except that such term does not include—
(i) an implant or article similar to an implant;
(ii) an article that applies radiation from outside of the body; or
(iii) the radiation source of an article described in clause (i) or (ii).
(C) The term “OTC monograph drug” has the meaning given such term in section 379j–71 of this title.
(3) Nothing in this subsection shall be construed as allowing for the classification of a product as a drug (as defined in section 321(g) of this title) if such product—
(A) is not described in paragraph (1); and
(B) meets the definition of a device under section 321(h) of this title,
unless another provision of this chapter otherwise indicates a different classification.
(4) The Secretary shall waive the application fee under sections 379h and 379j–42 of this title for applications for drugs that are—
(A) on September 30, 2022, legally marketed as devices; and
(B) deemed drugs pursuant to paragraph (1) 5
5 So in original. Probably should be followed by a period.
(June 25, 1938, ch. 675, § 503, 52 Stat. 1051; Oct. 26, 1951, ch. 578, § 1, 65 Stat. 648; Pub. L. 87–781, title I, § 104(e)(2), Oct. 10, 1962, 76 Stat. 785; Pub. L. 91–601, § 6(e), formerly § 7(e), Dec. 30, 1970, 84 Stat. 1673, renumbered Pub. L. 97–35, title XII, § 1205(c), Aug. 13, 1981, 95 Stat. 716; Pub. L. 100–293, §§ 4–6, Apr. 22, 1988, 102 Stat. 96–98; Pub. L. 100–670, title I, § 105, Nov. 16, 1988, 102 Stat. 3983; Pub. L. 101–629, § 16(a), Nov. 28, 1990, 104 Stat. 4526; Pub. L. 102–108, § 2(d), Aug. 17, 1991, 105 Stat. 550; Pub. L. 102–300, § 6(d), June 16, 1992, 106 Stat. 240; Pub. L. 102–353, §§ 2(a)–(c), 4, Aug. 26, 1992, 106 Stat. 941, 942; Pub. L. 104–250, § 5(a), Oct. 9, 1996, 110 Stat. 3155; Pub. L. 105–115, title I, §§ 123(e), 126(a), (c)(1), (2), Nov. 21, 1997, 111 Stat. 2324, 2327, 2328; Pub. L. 107–250, title II, § 204, Oct. 26, 2002, 116 Stat. 1611; Pub. L. 108–282, title I, § 102(b)(5)(F), Aug. 2, 2004, 118 Stat. 903; Pub. L. 113–54, title II, § 204(a)(1)–(4), (b), Nov. 27, 2013, 127 Stat. 630–635; Pub. L. 114–255, div. A, title III, § 3038(a), Dec. 13, 2016, 130 Stat. 1105; Pub. L. 117–328, div. FF, title III, § 3621, Dec. 29, 2022, 136 Stat. 5877.)

CITE AS: 21 USC 353

§ 353a. Pharmacy compounding
(a) In generalSections 351(a)(2)(B), 352(f)(1), and 355 of this title shall not apply to a drug product if the drug product is compounded for an identified individual patient based on the receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient, if the drug product meets the requirements of this section, and if the compounding—
(1) is by—
(A) a licensed pharmacist in a State licensed pharmacy or a Federal facility, or
(B) a licensed physician,
on the prescription order for such individual patient made by a licensed physician or other licensed practitioner authorized by State law to prescribe drugs; or
(2)
(A) is by a licensed pharmacist or licensed physician in limited quantities before the receipt of a valid prescription order for such individual patient; and
(B) is based on a history of the licensed pharmacist or licensed physician receiving valid prescription orders for the compounding of the drug product, which orders have been generated solely within an established relationship between—
(i) the licensed pharmacist or licensed physician; and
(ii)(I) such individual patient for whom the prescription order will be provided; or(II) the physician or other licensed practitioner who will write such prescription order.
(b) Compounded drug
(1) Licensed pharmacist and licensed physicianA drug product may be compounded under subsection (a) if the licensed pharmacist or licensed physician—
(A) compounds the drug product using bulk drug substances, as defined in regulations of the Secretary published at section 207.3(a)(4) of title 21 of the Code of Federal Regulations—
(i) that—(I) comply with the standards of an applicable United States Pharmacopoeia or National Formulary monograph, if a monograph exists, and the United States Pharmacopoeia chapter on pharmacy compounding;(II) if such a monograph does not exist, are drug substances that are components of drugs approved by the Secretary; or(III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, that appear on a list developed by the Secretary through regulations issued by the Secretary under subsection (c);
(ii) that are manufactured by an establishment that is registered under section 360 of this title (including a foreign establishment that is registered under section 360(i) of this title); and
(iii) that are accompanied by valid certificates of analysis for each bulk drug substance;
(B) compounds the drug product using ingredients (other than bulk drug substances) that comply with the standards of an applicable United States Pharmacopoeia or National Formulary monograph, if a monograph exists, and the United States Pharmacopoeia chapter on pharmacy compounding;
(C) does not compound a drug product that appears on a list published by the Secretary in the Federal Register of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective; and
(D) does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product.
(2) Definition
(3) Drug productA drug product may be compounded under subsection (a) only if—
(A) such drug product is not a drug product identified by the Secretary by regulation as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product; and
(B) such drug product is compounded in a State—
(i) that has entered into a memorandum of understanding with the Secretary which addresses the distribution of inordinate amounts of compounded drug products interstate and provides for appropriate investigation by a State agency of complaints relating to compounded drug products distributed outside such State; or
(ii) that has not entered into the memorandum of understanding described in clause (i) and the licensed pharmacist, licensed pharmacy, or licensed physician distributes (or causes to be distributed) compounded drug products out of the State in which they are compounded in quantities that do not exceed 5 percent of the total prescription orders dispensed or distributed by such pharmacy or physician.
The Secretary shall, in consultation with the National Association of Boards of Pharmacy, develop a standard memorandum of understanding for use by the States in complying with subparagraph (B)(i).
(c) Regulations
(1) In general
(2) Limiting compounding
(d) ApplicationThis section shall not apply to—
(1) compounded positron emission tomography drugs as defined in section 321(ii) of this title; or
(2) radiopharmaceuticals.
(e) “Compounding” defined
(June 25, 1938, ch. 675, § 503A, as added Pub. L. 105–115, title I, § 127(a), Nov. 21, 1997, 111 Stat. 2328; amended Pub. L. 113–54, title I, § 106(a), Nov. 27, 2013, 127 Stat. 598.)

CITE AS: 21 USC 353a

§ 353a–1. Enhanced communication
(a) Submissions from State boards of pharmacy
In a manner specified by the Secretary of Health and Human Services (referred to in this section as the “Secretary”), the Secretary shall receive submissions from State boards of pharmacy—
(1) describing actions taken against compounding pharmacies, as described in subsection (b); or
(2) expressing concerns that a compounding pharmacy may be acting contrary to section 353a of this title.
(b) Content of submissions from State boards of pharmacy
An action referred to in subsection (a)(1) is, with respect to a pharmacy that compounds drugs, any of the following:
(1) The issuance of a warning letter, or the imposition of sanctions or penalties, by a State for violations of a State’s pharmacy regulations pertaining to compounding.
(2) The suspension or revocation of a State-issued pharmacy license or registration for violations of a State’s pharmacy regulations pertaining to compounding.
(3) The recall of a compounded drug due to concerns relating to the quality or purity of such drug.
(c) Consultation
(d) Notifying State boards of pharmacy
The Secretary shall immediately notify State boards of pharmacy when—
(1) the Secretary receives a submission under subsection (a)(1); or
(2) the Secretary makes a determination that a pharmacy is acting contrary to section 353a of this title.
(Pub. L. 113–54, title I, § 105, Nov. 27, 2013, 127 Stat. 597.)

CITE AS: 21 USC 353a-1

§ 353b. Outsourcing facilities
(a) In generalSections 352(f)(1), 355, and 360eee–1 of this title shall not apply to a drug compounded by or under the direct supervision of a licensed pharmacist in a facility that elects to register as an outsourcing facility if each of the following conditions is met:
(1) Registration and reporting
(2) Bulk drug substancesThe drug is compounded in an outsourcing facility that does not compound using bulk drug substances (as defined in section 207.3(a)(4) of title 21, Code of Federal Regulations (or any successor regulation)), unless—
(A)
(i) the bulk drug substance appears on a list established by the Secretary identifying bulk drug substances for which there is a clinical need, by—(I) publishing a notice in the Federal Register proposing bulk drug substances to be included on the list, including the rationale for such proposal;(II) providing a period of not less than 60 calendar days for comment on the notice; and(III) publishing a notice in the Federal Register designating bulk drug substances for inclusion on the list; or
(ii) the drug compounded from such bulk drug substance appears on the drug shortage list in effect under section 356e of this title at the time of compounding, distribution, and dispensing;
(B) if an applicable monograph exists under the United States Pharmacopeia, the National Formulary, or another compendium or pharmacopeia recognized by the Secretary for purposes of this paragraph, the bulk drug substances each comply with the monograph;
(C) the bulk drug substances are each manufactured by an establishment that is registered under section 360 of this title (including a foreign establishment that is registered under section 360(i) of this title); and
(D) the bulk drug substances are each accompanied by a valid certificate of analysis.
(3) Ingredients (other than bulk drug substances)
(4) Drugs withdrawn or removed because unsafe or not effective
(5) Essentially a copy of an approved drug
(6) Drugs presenting demonstrable difficulties for compoundingThe drug—
(A) is not identified (directly or as part of a category of drugs) on a list published by the Secretary, through the process described in subsection (c), of drugs or categories of drugs that present demonstrable difficulties for compounding that are reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug or category of drugs, taking into account the risks and benefits to patients; or
(B) is compounded in accordance with all applicable conditions identified on the list described in subparagraph (A) as conditions that are necessary to prevent the drug or category of drugs from presenting the demonstrable difficulties described in subparagraph (A).
(7) Elements to assure safe use
(8) Prohibition on wholesaling
(9) Fees
(10) Labeling of drugs
(A) LabelThe label of the drug includes—
(i) the statement “This is a compounded drug.” or a reasonable comparable alternative statement (as specified by the Secretary) that prominently identifies the drug as a compounded drug;
(ii) the name, address, and phone number of the applicable outsourcing facility; and
(iii) with respect to the drug—(I) the lot or batch number;(II) the established name of the drug;(III) the dosage form and strength;(IV) the statement of quantity or volume, as appropriate;(V) the date that the drug was compounded;(VI) the expiration date;(VII) storage and handling instructions;(VIII) the National Drug Code number, if available;(IX) the statement “Not for resale”, and, if the drug is dispensed or distributed other than pursuant to a prescription for an individual identified patient, the statement “Office Use Only”; and(X) subject to subparagraph (B)(i), a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingredient.
(B) ContainerThe container from which the individual units of the drug are removed for dispensing or for administration (such as a plastic bag containing individual product syringes) shall include—
(i) the information described under subparagraph (A)(iii)(X), if there is not space on the label for such information;
(ii) the following information to facilitate adverse event reporting: www.fda.gov/medwatch and 1–800–FDA–1088 (or any successor Internet Web site or phone number); and
(iii) directions for use, including, as appropriate, dosage and administration.
(C) Additional information
(11) Outsourcing facility requirement
(b) Registration of outsourcing facilities and reporting of drugs
(1) Registration of outsourcing facilities
(A) Annual registrationUpon electing and in order to become an outsourcing facility, and during the period beginning on October 1 and ending on December 31 of each year thereafter, a facility—
(i) shall register with the Secretary its name, place of business, and unique facility identifier (which shall conform to the requirements for the unique facility identifier established under section 360 of this title), and a point of contact email address; and
(ii) shall indicate whether the outsourcing facility intends to compound a drug that appears on the list in effect under section 356e of this title during the subsequent calendar year.
(B) Availability of registration for inspection; list
(i) Registrations
(ii) List
(2) Drug reporting by outsourcing facilities
(A) In generalUpon initially registering as an outsourcing facility, once during the month of June of each year, and once during the month of December of each year, each outsourcing facility that registers with the Secretary under paragraph (1) shall submit to the Secretary a report—
(i) identifying the drugs compounded by such outsourcing facility during the previous 6-month period; and
(ii) with respect to each drug identified under clause (i), providing the active ingredient, the source of such active ingredient, the National Drug Code number of the source drug or bulk active ingredient, if available, the strength of the active ingredient per unit, the dosage form and route of administration, the package description, the number of individual units produced, and the National Drug Code number of the final product, if assigned.
(B) Form
(C) Confidentiality
(3) Electronic registration and reporting
(4) Risk-based inspection frequency
(A) In generalOutsourcing facilities—
(i) shall be subject to inspection pursuant to section 374 of this title; and
(ii) shall not be eligible for the exemption under section 374(a)(2)(A) of this title.
(B) Risk-based schedule
(C) Risk factorsIn establishing the risk-based schedule, the Secretary shall inspect outsourcing facilities according to the known safety risks of such outsourcing facilities, which shall be based on the following factors:
(i) The compliance history of the outsourcing facility.
(ii) The record, history, and nature of recalls linked to the outsourcing facility.
(iii) The inherent risk of the drugs compounded at the outsourcing facility.
(iv) The inspection frequency and history of the outsourcing facility, including whether the outsourcing facility has been inspected pursuant to section 374 of this title within the last 4 years.
(v) Whether the outsourcing facility has registered under this paragraph as an entity that intends to compound a drug that appears on the list in effect under section 356e of this title.
(vi) Any other criteria deemed necessary and appropriate by the Secretary for purposes of allocating inspection resources.
(5) Adverse event reporting
(c) Regulations
(1) In general
(2) Advisory committee on compounding
(3) Interim list
(A) In generalBefore the effective date of the regulations finalized to implement subsection (a)(6), the Secretary may designate drugs, categories of drugs, or conditions as described such 1
1 So in original.
subsection by—
(i) publishing a notice of such substances, drugs, categories of drugs, or conditions proposed for designation, including the rationale for such designation, in the Federal Register;
(ii) providing a period of not less than 60 calendar days for comment on the notice; and
(iii) publishing a notice in the Federal Register designating such drugs, categories of drugs, or conditions.
(B) Sunset of noticeAny notice provided under subparagraph (A) shall not be effective after the earlier of—
(i) the date that is 5 years after November 27, 2013; or
(ii) the effective date of the final regulations issued to implement subsection (a)(6).
(4) Updates
(d)2
2 So in original. Two subsecs. (d) have been enacted.
DefinitionsIn this section:
(1) The term “compounding” includes the combining, admixing, mixing, diluting, pooling, reconstituting, or otherwise altering of a drug or bulk drug substance to create a drug.
(2) The term “essentially a copy of an approved drug” means—
(A) a drug that is identical or nearly identical to an approved drug, or a marketed drug not subject to section 353(b) of this title and not subject to approval in an application submitted under section 355 of this title, unless, in the case of an approved drug, the drug appears on the drug shortage list in effect under section 356e of this title at the time of compounding, distribution, and dispensing; or
(B) a drug, a component of which is a bulk drug substance that is a component of an approved drug or a marketed drug that is not subject to section 353(b) of this title and not subject to approval in an application submitted under section 355 of this title, unless there is a change that produces for an individual patient a clinical difference, as determined by the prescribing practitioner, between the compounded drug and the comparable approved drug.
(3) The term “approved drug” means a drug that is approved under section 355 of this title and does not appear on the list described in subsection (a)(4) of drugs that have been withdrawn or removed from the market because such drugs or components of such drugs have been found to be unsafe or not effective.
(4)
(A) The term “outsourcing facility” means a facility at one geographic location or address that—
(i) is engaged in the compounding of sterile drugs;
(ii) has elected to register as an outsourcing facility; and
(iii) complies with all of the requirements of this section.
(B) An outsourcing facility is not required to be a licensed pharmacy.
(C) An outsourcing facility may or may not obtain prescriptions for identified individual patients.
(5) The term “sterile drug” means a drug that is intended for parenteral administration, an ophthalmic or oral inhalation drug in aqueous format, or a drug that is required to be sterile under Federal or State law.
(d)2 Obligation to pay fees
(June 25, 1938, ch. 675, § 503B, as added Pub. L. 113–54, title I, § 102(a)(2), Nov. 27, 2013, 127 Stat. 588.)

CITE AS: 21 USC 353b

§ 353c. Prereview of television advertisements
(a) In general
(b) ReviewIn conducting a review of a television advertisement under this section, the Secretary may make recommendations with respect to information included in the label of the drug—
(1) on changes that are—
(A) necessary to protect the consumer good and well-being; or
(B) consistent with prescribing information for the product under review; and
(2) if appropriate and if information exists, on statements for inclusion in the advertisement to address the specific efficacy of the drug as it relates to specific population groups, including elderly populations, children, and racial and ethnic minorities.
(c) No authority to require changes
(d) Elderly populations, children, racially and ethnically diverse communities
(e) Specific disclosures
(1) Serious risk; safety protocol
(2) Date of approval
(f) Rule of construction
(June 25, 1938, ch. 675, § 503C, formerly § 503B, as added Pub. L. 110–85, title IX, § 901(d)(2), Sept. 27, 2007, 121 Stat. 939, renumbered § 503C, Pub. L. 113–54, title I, § 102(a)(1), Nov. 27, 2013, 127 Stat. 587.)

CITE AS: 21 USC 353c

§ 353d. Process to update labeling for certain generic drugs
(a) DefinitionsFor purposes of this section:
(1) The term “covered drug” means a drug approved under section 355(c) of this title—
(A) for which there are no unexpired patents included in the list under section 355(j)(7) of this title and no unexpired period of exclusivity;
(B) for which the approval of the application has been withdrawn for reasons other than safety or effectiveness; and
(C) for which—
(i)(I) there is new scientific evidence available pertaining to new or existing conditions of use that is not reflected in the approved labeling;(II) the approved labeling does not reflect current legal and regulatory requirements for span or format; or(III) there is a relevant accepted use in clinical practice that is not reflected in the approved labeling; and
(ii) updating the approved labeling would benefit the public health.
(2) The term “period of exclusivity”, with respect to a drug approved under section 355(c) of this title, means any period of exclusivity under clause (ii), (iii), or (iv) of section 355(c)(3)(E) of this title, clause (ii), (iii), or (iv) of section 355(j)(5)(F) of this title, or section 355a, 355f, or 360cc of this title.
(3) The term “generic version” means a drug approved under section 355(j) of this title whose reference listed drug is a covered drug.
(4) The term “relevant accepted use” means a use for a drug in clinical practice that is supported by scientific evidence that appears to the Secretary to meet the standards for approval under section 355 of this title.
(5) The term “selected drug” means a covered drug for which the Secretary has determined through the process under subsection (c) that the labeling should be changed.
(b) Identification of covered drugsThe Secretary may identify covered drugs for which labeling updates would provide a public health benefit. To assist in identifying covered drugs, the Secretary may do one or both of the following:
(1) Enter into cooperative agreements or contracts with public or private entities to review the available scientific evidence concerning such drugs.
(2) Seek public input concerning such drugs, including input on whether there is a relevant accepted use in clinical practice that is not reflected in the approved labeling of such drugs or whether new scientific evidence is available regarding the conditions of use for such drug, by—
(A) holding one or more public meetings;
(B) opening a public docket for the submission of public comments; or
(C) other means, as the Secretary determines appropriate.
(c) Selection of drugs for updating
(d) Initiation of the process of updatingIf the Secretary determines that labeling changes are appropriate for a selected drug pursuant to subsection (c), the Secretary shall provide notice to the holders of approved applications for a generic version of such drug that—
(1) summarizes the findings supporting the determination of the Secretary that the available scientific evidence meets the standards under section 355 of this title for adding or modifying information or providing supplemental information to the labeling of the covered drug pursuant to subsection (c);
(2) provides a clear statement regarding the additional, modified, or supplemental information for such labeling, according to the determination by the Secretary (including, as applicable, modifications to add the relevant accepted use to the labeling of the drug as an additional indication for the drug); and
(3) states whether the statement under paragraph (2) applies to the selected drug as a class of covered drugs or only to a specific drug product.
(e) Response to notificationWithin 30 days of receipt of notification provided by the Secretary pursuant to subsection (d), the holder of an approved application for a generic version of the selected drug shall—
(1) agree to change the approved labeling to reflect the additional, modified, or supplemental information the Secretary has determined to be appropriate; or
(2) notify the Secretary that the holder of the approved application does not believe that the requested labeling changes are warranted and submit a statement detailing the reasons why such changes are not warranted.
(f) Review of application holder’s response
(1) In general
(2) Changes to labelingAfter considering all responses from the holder of an approved application under paragraph (1) or (2) of subsection (e), and any discussion under paragraph (1), the Secretary may order such holder to make the labeling changes the Secretary determines are appropriate. Such holder of an approved application shall—
(A) update its paper labeling for the drug at the next printing of that labeling;
(B) update any electronic labeling for the drug within 30 days of such order; and
(C) submit the revised labeling through the form, “Supplement—Changes Being Effected”.
(g) Violation
(h) Limitations; generic drugs
(1) In general
(2) Supplemental applications
(3) Selection of drugs
(i) Rules of construction
(1) Approval standards
(2) Removal of information
(3) Secretary authority
(4) Maintenance of labeling
(j) ReportsNot later than 4 years after December 27, 2020, and every 4 years thereafter, the Secretary shall prepare and submit to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate, a report that—
(1) describes the actions of the Secretary under this section, including—
(A) the number of covered drugs and description of the types of drugs the Secretary has selected for labeling changes and the rationale for such recommended changes; and
(B) the number of times the Secretary entered into discussions concerning a disagreement with an application holder or holders and a summary of the decision regarding a labeling change, if any; and
(2) includes any recommendations of the Secretary for modifying the program under this section.
(June 25, 1938, ch. 675, § 503D, as added Pub. L. 116–260, div. BB, title III, § 324, Dec. 27, 2020, 134 Stat. 2933.)

CITE AS: 21 USC 353d

§ 354. Veterinary feed directive drugs
(a) Lawful veterinary feed directive requirement
(1) A drug intended for use in or on animal feed which is limited by an approved application filed pursuant to section 360b(b) of this title, a conditionally-approved application filed pursuant to section 360ccc of this title, or an index listing pursuant to section 360ccc–1 of this title to use under the professional supervision of a licensed veterinarian is a veterinary feed directive drug. Any animal feed bearing or containing a veterinary feed directive drug shall be fed to animals only by or upon a lawful veterinary feed directive issued by a licensed veterinarian in the course of the veterinarian’s professional practice. When labeled, distributed, held, and used in accordance with this section, a veterinary feed directive drug and any animal feed bearing or containing a veterinary feed directive drug shall be exempt from section 352(f) of this title.
(2) A veterinary feed directive is lawful if it—
(A) contains such information as the Secretary may by general regulation or by order require; and
(B) is in compliance with the conditions and indications for use of the drug set forth in the notice published pursuant to section 360b(i) of this title, or the index listing pursuant to section 360ccc–1(e) of this title.
(3)
(A) Any persons involved in the distribution or use of animal feed bearing or containing a veterinary feed directive drug and the licensed veterinarian issuing the veterinary feed directive shall maintain a copy of the veterinary feed directive applicable to each such feed, except in the case of a person distributing such feed to another person for further distribution. Such person distributing the feed shall maintain a written acknowledgment from the person to whom the feed is shipped stating that that person shall not ship or move such feed to an animal production facility without a veterinary feed directive or ship such feed to another person for further distribution unless that person has provided the same written acknowledgment to its immediate supplier.
(B) Every person required under subparagraph (A) to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(C) Any person who distributes animal feed bearing or containing a veterinary feed directive drug shall upon first engaging in such distribution notify the Secretary of that person’s name and place of business. The failure to provide such notification shall be deemed to be an act which results in the drug being misbranded.
(b) Labeling and advertising
(c) Nonprescription status
(June 25, 1938, ch. 675, § 504, as added Pub. L. 104–250, § 5(b), Oct. 9, 1996, 110 Stat. 3155; amended Pub. L. 108–282, title I, § 102(b)(5)(G), (H), Aug. 2, 2004, 118 Stat. 903.)

CITE AS: 21 USC 354

§ 355. New drugs
(a) Necessity of effective approval of application
(b) Filing application; contents
(1)
(A) Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a). Such persons shall submit to the Secretary as part of the application—
(i) full reports of investigations which have been made to show whether such drug is safe for use and whether such drug is effective in use;
(ii) a full list of the articles used as components of such drug;
(iii) a full statement of the composition of such drug;
(iv) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug;
(v) such samples of such drug and of the articles used as components thereof as the Secretary may require;
(vi) specimens of the labeling proposed to be used for such drug;
(vii) any assessments required under section 355c of this title; and
(viii) the patent number and expiration date of each patent for which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use, or sale of the drug, and that—(I) claims the drug for which the applicant submitted the application and is a drug substance (active ingredient) patent or a drug product (formulation or composition) patent; or(II) claims a method of using such drug for which approval is sought or has been granted in the application.
(B) If an application is filed under this subsection for a drug, and a patent of the type described in subparagraph (A)(viii) is issued after the filing date but before approval of the application, the applicant shall amend the application to include the patent number and expiration date.
(2) An application submitted under paragraph (1) for a drug for which the investigations described in clause (A) of such paragraph and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted shall also include—
(A) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the drug for which such investigations were conducted or which claims a use for such drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under paragraph (1) or subsection (c)—
(i) that such patent information has not been filed,
(ii) that such patent has expired,
(iii) of the date on which such patent will expire, or
(iv) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug for which the application is submitted; and
(B) if with respect to the drug for which investigations described in paragraph (1)(A) were conducted information was filed under paragraph (1) or subsection (c) for a method of use patent which does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use.
(3)Notice of opinion that patent is invalid or will not be infringed.—
(A)Agreement to give notice.—An applicant that makes a certification described in paragraph (2)(A)(iv) shall include in the application a statement that the applicant will give notice as required by this paragraph.
(B)Timing of notice.—An applicant that makes a certification described in paragraph (2)(A)(iv) shall give notice as required under this paragraph—
(i) if the certification is in the application, not later than 20 days after the date of the postmark on the notice with which the Secretary informs the applicant that the application has been filed; or
(ii) if the certification is in an amendment or supplement to the application, at the time at which the applicant submits the amendment or supplement, regardless of whether the applicant has already given notice with respect to another such certification contained in the application or in an amendment or supplement to the application.
(C)Recipients of notice.—An applicant required under this paragraph to give notice shall give notice to—
(i) each owner of the patent that is the subject of the certification (or a representative of the owner designated to receive such a notice); and
(ii) the holder of the approved application under this subsection for the drug that is claimed by the patent or a use of which is claimed by the patent (or a representative of the holder designated to receive such a notice).
(D)Contents of notice.—A notice required under this paragraph shall—
(i) state that an application that contains data from bioavailability or bioequivalence studies has been submitted under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of the drug before the expiration of the patent referred to in the certification; and
(ii) include a detailed statement of the factual and legal basis of the opinion of the applicant that the patent is invalid or will not be infringed.
(4)
(A) An applicant may not amend or supplement an application referred to in paragraph (2) to seek approval of a drug that is a different drug than the drug identified in the application as submitted to the Secretary.
(B) With respect to the drug for which such an application is submitted, nothing in this subsection or subsection (c)(3) prohibits an applicant from amending or supplementing the application to seek approval of a different strength.
(5)
(A) The Secretary shall issue guidance for the individuals who review applications submitted under paragraph (1) or under section 262 of title 42, which shall relate to promptness in conducting the review, technical excellence, lack of bias and conflict of interest, and knowledge of regulatory and scientific standards, and which shall apply equally to all individuals who review such applications.
(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection or section 262 of title 42 if the sponsor or applicant makes a reasonable written request for a meeting for the purpose of reaching agreement on the design and size—
(i)(I) of clinical trials intended to form the primary basis of an effectiveness claim; or(II) in the case where human efficacy studies are not ethical or feasible, of animal and any associated clinical trials which, in combination, are intended to form the primary basis of an effectiveness claim; or
(ii) with respect to an application for approval of a biological product under section 262(k) of title 42, of any necessary clinical study or studies.
The sponsor or applicant shall provide information necessary for discussion and agreement on the design and size of the clinical trials. Minutes of any such meeting shall be prepared by the Secretary and made available to the sponsor or applicant upon request.
(C) Any agreement regarding the parameters of the design and size of clinical trials of a new drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
(E) The written decisions of the reviewing division shall be binding upon, and may not directly or indirectly be changed by, the field or compliance division personnel unless such field or compliance division personnel demonstrate to the reviewing division why such decision should be modified.
(F) No action by the reviewing division may be delayed because of the unavailability of information from or action by field personnel unless the reviewing division determines that a delay is necessary to assure the marketing of a safe and effective drug.
(G) For purposes of this paragraph, the reviewing division is the division responsible for the review of an application for approval of a drug under this subsection or section 262 of title 42 (including all scientific and medical matters, chemistry, manufacturing, and controls).
(6) An application submitted under this subsection shall be accompanied by the certification required under section 282(j)(5)(B) of title 42. Such certification shall not be considered an element of such application.
(c) Period for approval of application; period for, notice, and expedition of hearing; period for issuance of order
(1) Within one hundred and eighty days after the filing of an application under subsection (b), or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either—
(A) approve the application if he then finds that none of the grounds for denying approval specified in subsection (d) applies, or
(B) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) on the question whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary’s order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(2) Not later than 30 days after the date of approval of an application submitted under subsection (b), the holder of the approved application shall file with the Secretary the patent number and the expiration date of any patent described in subsection (b)(1)(A)(viii), except that a patent that is identified as claiming a method of using such drug shall be filed only if the patent claims a method of use approved in the application. If a patent described in subsection (b)(1)(A)(viii) is issued after the date of approval of an application submitted under subsection (b), the holder of the approved application shall, not later than 30 days after the date of issuance of the patent, file the patent number and the expiration date of the patent, except that a patent that claims a method of using such drug shall be filed only if approval for such use has been granted in the application. If the patent information described in subsection (b) could not be filed with the submission of an application under subsection (b) because the application was filed before the patent information was required under subsection (b) or a patent was issued after the application was approved under such subsection, the holder of an approved application shall file with the Secretary the patent number and the expiration date of any patent described in subsection (b)(1)(A)(viii). If the holder of an approved application could not file patent information under subsection (b) because it was not required at the time the application was approved, the holder shall file such information under this subsection not later than thirty days after September 24, 1984, and if the holder of an approved application could not file patent information under subsection (b) because no patent of the type for which information is required to be submitted in subsection (b)(1)(A)(viii) had been issued when an application was filed or approved, the holder shall file such information under this subsection not later than thirty days after the date the patent involved is issued. Upon the submission of patent information under this subsection, the Secretary shall publish it. Patent information that is not the type of patent information required by subsection (b)(1)(A)(viii) shall not be submitted under this paragraph.
(3) The approval of an application filed under subsection (b) which contains a certification required by paragraph (2) of such subsection shall be made effective on the last applicable date determined by applying the following to each certification made under subsection (b)(2)(A):
(A) If the applicant only made a certification described in clause (i) or (ii) of subsection (b)(2)(A) or in both such clauses, the approval may be made effective immediately.
(B) If the applicant made a certification described in clause (iii) of subsection (b)(2)(A), the approval may be made effective on the date certified under clause (iii).
(C) If the applicant made a certification described in clause (iv) of subsection (b)(2)(A), the approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice described in subsection (b)(3) is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under paragraph (2) or subsection (b)(1) before the date on which the application (excluding an amendment or supplement to the application) was submitted. If such an action is brought before the expiration of such days, the approval may be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under subsection (b)(3) or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that—
(i) if before the expiration of such period the district court decides that the patent is invalid or not infringed (including any substantive determination that there is no cause of action for patent infringement or invalidity), the approval shall be made effective on—(I) the date on which the court enters judgment reflecting the decision; or(II) the date of a settlement order or consent decree signed and entered by the court stating that the patent that is the subject of the certification is invalid or not infringed;
(ii) if before the expiration of such period the district court decides that the patent has been infringed—(I) if the judgment of the district court is appealed, the approval shall be made effective on—(aa) the date on which the court of appeals decides that the patent is invalid or not infringed (including any substantive determination that there is no cause of action for patent infringement or invalidity); or(bb) the date of a settlement order or consent decree signed and entered by the court of appeals stating that the patent that is the subject of the certification is invalid or not infringed; or(II) if the judgment of the district court is not appealed or is affirmed, the approval shall be made effective on the date specified by the district court in a court order under section 271(e)(4)(A) of title 35;
(iii) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective as provided in clause (i); or
(iv) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent has been infringed, the approval shall be made effective as provided in clause (ii).
In such an action, each of the parties shall reasonably cooperate in expediting the action.
(D)Civil action to obtain patent certainty.—
(i)Declaratory judgment absent infringement action.—(I)In general.—No action may be brought under section 2201 of title 28 by an applicant referred to in subsection (b)(2) for a declaratory judgment with respect to a patent which is the subject of the certification referred to in subparagraph (C) unless—(aa) the 45-day period referred to in such subparagraph has expired;(bb) neither the owner of such patent nor the holder of the approved application under subsection (b) for the drug that is claimed by the patent or a use of which is claimed by the patent brought a civil action against the applicant for infringement of the patent before the expiration of such period; and(cc) in any case in which the notice provided under paragraph (2)(B) relates to noninfringement, the notice was accompanied by a document described in subclause (III).(II)Filing of civil action.—If the conditions described in items (aa), (bb), and as applicable, (cc) of subclause (I) have been met, the applicant referred to in such subclause may, in accordance with section 2201 of title 28, bring a civil action under such section against the owner or holder referred to in such subclause (but not against any owner or holder that has brought such a civil action against the applicant, unless that civil action was dismissed without prejudice) for a declaratory judgment that the patent is invalid or will not be infringed by the drug for which the applicant seeks approval, except that such civil action may be brought for a declaratory judgment that the patent will not be infringed only in a case in which the condition described in subclause (I)(cc) is applicable. A civil action referred to in this subclause shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business.(III)Offer of confidential access to application.—For purposes of subclause (I)(cc), the document described in this subclause is a document providing an offer of confidential access to the application that is in the custody of the applicant referred to in subsection (b)(2) for the purpose of determining whether an action referred to in subparagraph (C) should be brought. The document providing the offer of confidential access shall contain such restrictions as to persons entitled to access, and on the use and disposition of any information accessed, as would apply had a protective order been entered for the purpose of protecting trade secrets and other confidential business information. A request for access to an application under an offer of confidential access shall be considered acceptance of the offer of confidential access with the restrictions as to persons entitled to access, and on the use and disposition of any information accessed, contained in the offer of confidential access, and those restrictions and other terms of the offer of confidential access shall be considered terms of an enforceable contract. Any person provided an offer of confidential access shall review the application for the sole and limited purpose of evaluating possible infringement of the patent that is the subject of the certification under subsection (b)(2)(A)(iv) and for no other purpose, and may not disclose information of no relevance to any issue of patent infringement to any person other than a person provided an offer of confidential access. Further, the application may be redacted by the applicant to remove any information of no relevance to any issue of patent infringement.
(ii)Counterclaim to infringement action.—(I)In general.—If an owner of the patent or the holder of the approved application under subsection (b) for the drug that is claimed by the patent or a use of which is claimed by the patent brings a patent infringement action against the applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder under subsection (b) or this subsection on the ground that the patent does not claim either—(aa) the drug for which the application was approved; or(bb) an approved method of using the drug.(II)Subclause (I) does not authorize the assertion of a claim described in subclause (I) in any civil action or proceeding other than a counterclaim described in subclause (I).
(iii)No damages.—An applicant shall not be entitled to damages in a civil action under clause (i) or a counterclaim under clause (ii).
(E)
(i) Repealed. Pub. L. 117–9, § 1(b)(1)(A), Apr. 23, 2021, 135 Stat. 258.
(ii) If an application submitted under subsection (b) for a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under subsection (b), is approved after September 24, 1984, no application which refers to the drug for which the subsection (b) application was submitted and for which the investigations described in subsection (b)(1)(A)(i) and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted may be submitted under subsection (b) before the expiration of five years from the date of the approval of the application under subsection (b), except that such an application may be submitted under subsection (b) after the expiration of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in clause (iv) of subsection (b)(2)(A). The approval of such an application shall be made effective in accordance with this paragraph except that, if an action for patent infringement is commenced during the one-year period beginning forty-eight months after the date of the approval of the subsection (b) application, the thirty-month period referred to in subparagraph (C) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(iii) If an application submitted under subsection (b) for a drug, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) that has been approved in another application approved under subsection (b), is approved after September 24, 1984, and if such application contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under subsection (b) for the conditions of approval of such drug in the approved subsection (b) application effective before the expiration of three years from the date of the approval of the application under subsection (b) if the investigations described in subsection (b)(1)(A)(i) and relied upon by the applicant for approval of the application were not conducted by or for the applicant and if the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.
(iv) If a supplement to an application approved under subsection (b) is approved after September 24, 1984, and the supplement contains reports of new clinical investigations (other than bioavailabilty 1
1 So in original. Probably should be “bioavailability”.
studies) essential to the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under subsection (b) for a change approved in the supplement effective before the expiration of three years from the date of the approval of the supplement under subsection (b) if the investigations described in subsection (b)(1)(A)(i) and relied upon by the applicant for approval of the application were not conducted by or for the applicant and if the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.
(v) If an application (or supplement to an application) submitted under subsection (b) for a drug, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) that has been approved in another application under subsection (b), was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection and for which the investigations described in subsection (b)(1)(A)(i) and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted and which refers to the drug for which the subsection (b) application was submitted effective before the expiration of two years from September 24, 1984.
(4) A drug manufactured in a pilot or other small facility may be used to demonstrate the safety and effectiveness of the drug and to obtain approval for the drug prior to manufacture of the drug in a larger facility, unless the Secretary makes a determination that a full scale production facility is necessary to ensure the safety or effectiveness of the drug.
(5)
(A) The Secretary may rely upon qualified data summaries to support the approval of a supplemental application, with respect to a qualified indication for a drug, submitted under subsection (b), if such supplemental application complies with subparagraph (B).
(B) A supplemental application is eligible for review as described in subparagraph (A) only if—
(i) there is existing data available and acceptable to the Secretary demonstrating the safety of the drug; and
(ii) all data used to develop the qualified data summaries are submitted to the Secretary as part of the supplemental application.
(C) The Secretary shall post on the Internet website of the Food and Drug Administration and update annually—
(i) the number of applications reviewed solely under subparagraph (A) or section 262(a)(2)(E) of title 42;
(ii) the average time for completion of review under subparagraph (A) or section 262(a)(2)(E) of title 42;
(iii) the average time for review of supplemental applications where the Secretary did not use review flexibility under subparagraph (A) or section 262(a)(2)(E) of title 42; and
(iv) the number of applications reviewed under subparagraph (A) or section 262(a)(2)(E) of title 42 for which the Secretary made use of full data sets in addition to the qualified data summary.
(D) In this paragraph—
(i) the term “qualified indication” means an indication for a drug that the Secretary determines to be appropriate for summary level review under this paragraph; and
(ii) the term “qualified data summary” means a summary of clinical data that demonstrates the safety and effectiveness of a drug with respect to a qualified indication.
(d) Grounds for refusing application; approval of application; “substantial evidence” defined
(e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to public health
(f) Revocation of order refusing, withdrawing or suspending approval of application
(g) Service of orders
(h) Appeal from order
(i) Exemptions of drugs for research; discretionary and mandatory conditions; direct reports to Secretary
(1) The Secretary shall promulgate regulations for exempting from the operation of the foregoing subsections of this section drugs intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of drugs. Such regulations may, within the discretion of the Secretary, among other conditions relating to the protection of the public health, provide for conditioning such exemption upon—
(A) the submission to the Secretary, before any clinical testing of a new drug is undertaken, of reports, by the manufacturer or the sponsor of the investigation of such drug, of nonclinical tests of such drug adequate to justify the proposed clinical testing;
(B) the manufacturer or the sponsor of the investigation of a new drug proposed to be distributed to investigators for clinical testing obtaining a signed agreement from each of such investigators that patients to whom the drug is administered will be under his personal supervision, or under the supervision of investigators responsible to him, and that he will not supply such drug to any other investigator, or to clinics, for administration to human beings;
(C) the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such drug, of data (including but not limited to analytical reports by investigators) obtained as the result of such investigational use of such drug, as the Secretary finds will enable him to evaluate the safety and effectiveness of such drug in the event of the filing of an application pursuant to subsection (b); and
(D) the submission to the Secretary by the manufacturer or the sponsor of the investigation of a new drug of a statement of intent regarding whether the manufacturer or sponsor has plans for assessing pediatric safety and efficacy.
(2) Subject to paragraph (3), a clinical investigation of a new drug may begin 30 days after the Secretary has received from the manufacturer or sponsor of the investigation a submission containing such information about the drug and the clinical investigation, including—
(A) information on design of the investigation and adequate reports of basic information, certified by the applicant to be accurate reports, necessary to assess the safety of the drug for use in clinical investigation; and
(B) adequate information on the chemistry and manufacturing of the drug, controls available for the drug, and primary data tabulations from nonclinical tests or human studies.
(3)
(A) At any time, the Secretary may prohibit the sponsor of an investigation from conducting the investigation (referred to in this paragraph as a “clinical hold”) if the Secretary makes a determination described in subparagraph (B). The Secretary shall specify the basis for the clinical hold, including the specific information available to the Secretary which served as the basis for such clinical hold, and confirm such determination in writing.
(B) For purposes of subparagraph (A), a determination described in this subparagraph with respect to a clinical hold is that—
(i) the drug involved represents an unreasonable risk to the safety of the persons who are the subjects of the clinical investigation, taking into account the qualifications of the clinical investigators, information about the drug, the design of the clinical investigation, the condition for which the drug is to be investigated, and the health status of the subjects involved; or
(ii) the clinical hold should be issued for such other reasons as the Secretary may by regulation establish (including reasons established by regulation before November 21, 1997).
(C) Any written request to the Secretary from the sponsor of an investigation that a clinical hold be removed shall receive a decision, in writing and specifying the reasons therefor, within 30 days after receipt of such request. Any such request shall include sufficient information to support the removal of such clinical hold.
(4) Regulations under paragraph (1) shall provide that such exemption shall be conditioned upon the manufacturer, or the sponsor of the investigation, requiring that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where it is not feasible, it is contrary to the best interests of such human beings, or the proposed clinical testing poses no more than minimal risk to such human beings and includes appropriate safeguards as prescribed to protect the rights, safety, and welfare of such human beings. Nothing in this subsection shall be construed to require any clinical investigator to submit directly to the Secretary reports on the investigational use of drugs. The Secretary shall update such regulations to require inclusion in the informed consent documents and process a statement that clinical trial information for such clinical investigation has been or will be submitted for inclusion in the registry data bank pursuant to subsection (j) of section 282 of title 42.
(j) Abbreviated new drug applications
(1) Any person may file with the Secretary an abbreviated application for the approval of a new drug.
(2)
(A) An abbreviated application for a new drug shall contain—
(i) information to show that the conditions of use prescribed, recommended, or suggested in the labeling proposed for the new drug have been previously approved for a drug listed under paragraph (7) (hereinafter in this subsection referred to as a “listed drug”);
(ii)(I) if the listed drug referred to in clause (i) has only one active ingredient, information to show that the active ingredient of the new drug is the same as that of the listed drug;(II) if the listed drug referred to in clause (i) has more than one active ingredient, information to show that the active ingredients of the new drug are the same as those of the listed drug, or(III) if the listed drug referred to in clause (i) has more than one active ingredient and if one of the active ingredients of the new drug is different and the application is filed pursuant to the approval of a petition filed under subparagraph (C), information to show that the other active ingredients of the new drug are the same as the active ingredients of the listed drug, information to show that the different active ingredient is an active ingredient of a listed drug or of a drug which does not meet the requirements of section 321(p) of this title, and such other information respecting the different active ingredient with respect to which the petition was filed as the Secretary may require;
(iii) information to show that the route of administration, the dosage form, and the strength of the new drug are the same as those of the listed drug referred to in clause (i) or, if the route of administration, the dosage form, or the strength of the new drug is different and the application is filed pursuant to the approval of a petition filed under subparagraph (C), such information respecting the route of administration, dosage form, or strength with respect to which the petition was filed as the Secretary may require;
(iv) information to show that the new drug is bioequivalent to the listed drug referred to in clause (i), except that if the application is filed pursuant to the approval of a petition filed under subparagraph (C), information to show that the active ingredients of the new drug are of the same pharmacological or therapeutic class as those of the listed drug referred to in clause (i) and the new drug can be expected to have the same therapeutic effect as the listed drug when administered to patients for a condition of use referred to in clause (i);
(v) information to show that the labeling proposed for the new drug is the same as the labeling approved for the listed drug referred to in clause (i) except for changes required because of differences approved under a petition filed under subparagraph (C) or because the new drug and the listed drug are produced or distributed by different manufacturers;
(vi) the items specified in clauses (ii) through (vi) of subsection (b)(1)(A);
(vii) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the listed drug referred to in clause (i) or which claims a use for such listed drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection (b) or (c)—(I) that such patent information has not been filed,(II) that such patent has expired,(III) of the date on which such patent will expire, or(IV) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug for which the application is submitted; and
(viii) if with respect to the listed drug referred to in clause (i) information was filed under subsection (b) or (c) for a method of use patent which does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use.
The Secretary may not require that an abbreviated application contain information in addition to that required by clauses (i) through (viii).
(B)Notice of opinion that patent is invalid or will not be infringed.—
(i)Agreement to give notice.—An applicant that makes a certification described in subparagraph (A)(vii)(IV) shall include in the application a statement that the applicant will give notice as required by this subparagraph.
(ii)Timing of notice.—An applicant that makes a certification described in subparagraph (A)(vii)(IV) shall give notice as required under this subparagraph—(I) if the certification is in the application, not later than 20 days after the date of the postmark on the notice with which the Secretary informs the applicant that the application has been filed; or(II) if the certification is in an amendment or supplement to the application, at the time at which the applicant submits the amendment or supplement, regardless of whether the applicant has already given notice with respect to another such certification contained in the application or in an amendment or supplement to the application.
(iii)Recipients of notice.—An applicant required under this subparagraph to give notice shall give notice to—(I) each owner of the patent that is the subject of the certification (or a representative of the owner designated to receive such a notice); and(II) the holder of the approved application under subsection (b) for the drug that is claimed by the patent or a use of which is claimed by the patent (or a representative of the holder designated to receive such a notice).
(iv)Contents of notice.—A notice required under this subparagraph shall—(I) state that an application that contains data from bioavailability or bioequivalence studies has been submitted under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of the drug before the expiration of the patent referred to in the certification; and(II) include a detailed statement of the factual and legal basis of the opinion of the applicant that the patent is invalid or will not be infringed.
(C) If a person wants to submit an abbreviated application for a new drug which has a different active ingredient or whose route of administration, dosage form, or strength differ from that of a listed drug, such person shall submit a petition to the Secretary seeking permission to file such an application. The Secretary shall approve or disapprove a petition submitted under this subparagraph within ninety days of the date the petition is submitted. The Secretary shall approve such a petition unless the Secretary finds—
(i) that investigations must be conducted to show the safety and effectiveness of the drug or of any of its active ingredients, the route of administration, the dosage form, or strength which differ from the listed drug; or
(ii) that any drug with a different active ingredient may not be adequately evaluated for approval as safe and effective on the basis of the information required to be submitted in an abbreviated application.
(D)
(i) An applicant may not amend or supplement an application to seek approval of a drug referring to a different listed drug from the listed drug identified in the application as submitted to the Secretary.
(ii) With respect to the drug for which an application is submitted, nothing in this subsection prohibits an applicant from amending or supplementing the application to seek approval of a different strength.
(iii) Within 60 days after December 8, 2003, the Secretary shall issue guidance defining the term “listed drug” for purposes of this subparagraph.
(3)
(A) The Secretary shall issue guidance for the individuals who review applications submitted under paragraph (1), which shall relate to promptness in conducting the review, technical excellence, lack of bias and conflict of interest, and knowledge of regulatory and scientific standards, and which shall apply equally to all individuals who review such applications.
(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection if the sponsor or applicant makes a reasonable written request for a meeting for the purpose of reaching agreement on the design and size of bioavailability and bioequivalence studies needed for approval of such application. The sponsor or applicant shall provide information necessary for discussion and agreement on the design and size of such studies. Minutes of any such meeting shall be prepared by the Secretary and made available to the sponsor or applicant.
(C) Any agreement regarding the parameters of design and size of bioavailability and bioequivalence studies of a drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
(E) The written decisions of the reviewing division shall be binding upon, and may not directly or indirectly be changed by, the field or compliance office personnel unless such field or compliance office personnel demonstrate to the reviewing division why such decision should be modified.
(F) No action by the reviewing division may be delayed because of the unavailability of information from or action by field personnel unless the reviewing division determines that a delay is necessary to assure the marketing of a safe and effective drug.
(G) For purposes of this paragraph, the reviewing division is the division responsible for the review of an application for approval of a drug under this subsection (including scientific matters, chemistry, manufacturing, and controls).
(4) Subject to paragraph (5), the Secretary shall approve an application for a drug unless the Secretary finds—
(A) the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug are inadequate to assure and preserve its identity, strength, quality, and purity;
(B) information submitted with the application is insufficient to show that each of the proposed conditions of use have been previously approved for the listed drug referred to in the application;
(C)
(i) if the listed drug has only one active ingredient, information submitted with the application is insufficient to show that the active ingredient is the same as that of the listed drug;
(ii) if the listed drug has more than one active ingredient, information submitted with the application is insufficient to show that the active ingredients are the same as the active ingredients of the listed drug, or
(iii) if the listed drug has more than one active ingredient and if the application is for a drug which has an active ingredient different from the listed drug, information submitted with the application is insufficient to show—(I) that the other active ingredients are the same as the active ingredients of the listed drug, or(II) that the different active ingredient is an active ingredient of a listed drug or a drug which does not meet the requirements of section 321(p) of this title,
or no petition to file an application for the drug with the different ingredient was approved under paragraph (2)(C);
(D)
(i) if the application is for a drug whose route of administration, dosage form, or strength of the drug is the same as the route of administration, dosage form, or strength of the listed drug referred to in the application, information submitted in the application is insufficient to show that the route of administration, dosage form, or strength is the same as that of the listed drug, or
(ii) if the application is for a drug whose route of administration, dosage form, or strength of the drug is different from that of the listed drug referred to in the application, no petition to file an application for the drug with the different route of administration, dosage form, or strength was approved under paragraph (2)(C);
(E) if the application was filed pursuant to the approval of a petition under paragraph (2)(C), the application did not contain the information required by the Secretary respecting the active ingredient, route of administration, dosage form, or strength which is not the same;
(F) information submitted in the application is insufficient to show that the drug is bioequivalent to the listed drug referred to in the application or, if the application was filed pursuant to a petition approved under paragraph (2)(C), information submitted in the application is insufficient to show that the active ingredients of the new drug are of the same pharmacological or therapeutic class as those of the listed drug referred to in paragraph (2)(A)(i) and that the new drug can be expected to have the same therapeutic effect as the listed drug when administered to patients for a condition of use referred to in such paragraph;
(G) information submitted in the application is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for the listed drug referred to in the application except for changes required because of differences approved under a petition filed under paragraph (2)(C) or because the drug and the listed drug are produced or distributed by different manufacturers;
(H) information submitted in the application or any other information available to the Secretary shows that (i) the inactive ingredients of the drug are unsafe for use under the conditions prescribed, recommended, or suggested in the labeling proposed for the drug, or (ii) the composition of the drug is unsafe under such conditions because of the type or quantity of inactive ingredients included or the manner in which the inactive ingredients are included;
(I) the approval under subsection (c) of the listed drug referred to in the application under this subsection has been withdrawn or suspended for grounds described in the first sentence of subsection (e), the Secretary has published a notice of opportunity for hearing to withdraw approval of the listed drug under subsection (c) for grounds described in the first sentence of subsection (e), the approval under this subsection of the listed drug referred to in the application under this subsection has been withdrawn or suspended under paragraph (6), or the Secretary has determined that the listed drug has been withdrawn from sale for safety or effectiveness reasons;
(J) the application does not meet any other requirement of paragraph (2)(A); or
(K) the application contains an untrue statement of material fact.
(5)
(A) Within one hundred and eighty days of the initial receipt of an application under paragraph (2) or within such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall approve or disapprove the application.
(B) The approval of an application submitted under paragraph (2) shall be made effective on the last applicable date determined by applying the following to each certification made under paragraph (2)(A)(vii):
(i) If the applicant only made a certification described in subclause (I) or (II) of paragraph (2)(A)(vii) or in both such subclauses, the approval may be made effective immediately.
(ii) If the applicant made a certification described in subclause (III) of paragraph (2)(A)(vii), the approval may be made effective on the date certified under subclause (III).
(iii) If the applicant made a certification described in subclause (IV) of paragraph (2)(A)(vii), the approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice described in paragraph (2)(B) is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under subsection (b)(1) or (c)(2) before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under paragraph (2)(B)(i) or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that—(I) if before the expiration of such period the district court decides that the patent is invalid or not infringed (including any substantive determination that there is no cause of action for patent infringement or invalidity), the approval shall be made effective on—(aa) the date on which the court enters judgment reflecting the decision; or(bb) the date of a settlement order or consent decree signed and entered by the court stating that the patent that is the subject of the certification is invalid or not infringed;(II) if before the expiration of such period the district court decides that the patent has been infringed—(aa) if the judgment of the district court is appealed, the approval shall be made effective on—(AA) the date on which the court of appeals decides that the patent is invalid or not infringed (including any substantive determination that there is no cause of action for patent infringement or invalidity); or(BB) the date of a settlement order or consent decree signed and entered by the court of appeals stating that the patent that is the subject of the certification is invalid or not infringed; or(bb) if the judgment of the district court is not appealed or is affirmed, the approval shall be made effective on the date specified by the district court in a court order under section 271(e)(4)(A) of title 35;(III) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective as provided in subclause (I); or(IV) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent has been infringed, the approval shall be made effective as provided in subclause (II).
In such an action, each of the parties shall reasonably cooperate in expediting the action.
(iv) 180-day exclusivity period.—(I)Effectiveness of application.—Subject to subparagraph (D), if the application contains a certification described in paragraph (2)(A)(vii)(IV) and is for a drug for which a first applicant has submitted an application containing such a certification, the application shall be made effective on the date that is 180 days after the date of the first commercial marketing of the drug (including the commercial marketing of the listed drug) by any first applicant.(II)Definitions.—In this paragraph:(aa) 180-day exclusivity period.—The term “180-day exclusivity period” means the 180-day period ending on the day before the date on which an application submitted by an applicant other than a first applicant could become effective under this clause.(bb)First applicant.—As used in this subsection, the term “first applicant” means an applicant that, on the first day on which a substantially complete application containing a certification described in paragraph (2)(A)(vii)(IV) is submitted for approval of a drug, submits a substantially complete application that contains and lawfully maintains a certification described in paragraph (2)(A)(vii)(IV) for the drug.(cc)Substantially complete application.—As used in this subsection, the term “substantially complete application” means an application under this subsection that on its face is sufficiently complete to permit a substantive review and contains all the information required by paragraph (2)(A).(dd)Tentative approval.—(AA)In general.—The term “tentative approval” means notification to an applicant by the Secretary that an application under this subsection meets the requirements of paragraph (2)(A), but cannot receive effective approval because the application does not meet the requirements of this subparagraph, there is a period of exclusivity for the listed drug under subparagraph (F) or section 355a of this title, or there is a 7-year period of exclusivity for the listed drug under section 360cc of this title.(BB)Limitation.—A drug that is granted tentative approval by the Secretary is not an approved drug and shall not have an effective approval until the Secretary issues an approval after any necessary additional review of the application.
(v) 180-day exclusivity period for competitive generic therapies.—(I)Effectiveness of application.—Subject to subparagraph (D)(iv), if the application is for a drug that is the same as a competitive generic therapy for which any first approved applicant has commenced commercial marketing, the application shall be made effective on the date that is 180 days after the date of the first commercial marketing of the competitive generic therapy (including the commercial marketing of the listed drug) by any first approved applicant.(II)Limitation.—The exclusivity period under subclause (I) shall not apply with respect to a competitive generic therapy that has previously received an exclusivity period under subclause (I).(III)Definitions.—In this clause and subparagraph (D)(iv):(aa) The term “competitive generic therapy” means a drug—(AA) that is designated as a competitive generic therapy under section 356h of this title; and(BB) for which there are no unexpired patents or exclusivities on the list of products described in section 355(j)(7)(A) of this title at the time of submission.(bb) The term “first approved applicant” means any applicant that has submitted an application that—(AA) is for a competitive generic therapy that is approved on the first day on which any application for such competitive generic therapy is approved;(BB) is not eligible for a 180-day exclusivity period under clause (iv) for the drug that is the subject of the application for the competitive generic therapy; and(CC) is not for a drug for which all drug versions have forfeited eligibility for a 180-day exclusivity period under clause (iv) pursuant to subparagraph (D).
(C)Civil action to obtain patent certainty.—
(i)Declaratory judgment absent infringement action.—(I)In general.—No action may be brought under section 2201 of title 28 by an applicant under paragraph (2) for a declaratory judgment with respect to a patent which is the subject of the certification referred to in subparagraph (B)(iii) unless—(aa) the 45-day period referred to in such subparagraph has expired;(bb) neither the owner of such patent nor the holder of the approved application under subsection (b) for the drug that is claimed by the patent or a use of which is claimed by the patent brought a civil action against the applicant for infringement of the patent before the expiration of such period; and(cc) in any case in which the notice provided under paragraph (2)(B) relates to noninfringement, the notice was accompanied by a document described in subclause (III).(II)Filing of civil action.—If the conditions described in items (aa), (bb), and as applicable, (cc) of subclause (I) have been met, the applicant referred to in such subclause may, in accordance with section 2201 of title 28, bring a civil action under such section against the owner or holder referred to in such subclause (but not against any owner or holder that has brought such a civil action against the applicant, unless that civil action was dismissed without prejudice) for a declaratory judgment that the patent is invalid or will not be infringed by the drug for which the applicant seeks approval, except that such civil action may be brought for a declaratory judgment that the patent will not be infringed only in a case in which the condition described in subclause (I)(cc) is applicable. A civil action referred to in this subclause shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business.(III)Offer of confidential access to application.—For purposes of subclause (I)(cc), the document described in this subclause is a document providing an offer of confidential access to the application that is in the custody of the applicant under paragraph (2) for the purpose of determining whether an action referred to in subparagraph (B)(iii) should be brought. The document providing the offer of confidential access shall contain such restrictions as to persons entitled to access, and on the use and disposition of any information accessed, as would apply had a protective order been entered for the purpose of protecting trade secrets and other confidential business information. A request for access to an application under an offer of confidential access shall be considered acceptance of the offer of confidential access with the restrictions as to persons entitled to access, and on the use and disposition of any information accessed, contained in the offer of confidential access, and those restrictions and other terms of the offer of confidential access shall be considered terms of an enforceable contract. Any person provided an offer of confidential access shall review the application for the sole and limited purpose of evaluating possible infringement of the patent that is the subject of the certification under paragraph (2)(A)(vii)(IV) and for no other purpose, and may not disclose information of no relevance to any issue of patent infringement to any person other than a person provided an offer of confidential access. Further, the application may be redacted by the applicant to remove any information of no relevance to any issue of patent infringement.
(ii)Counterclaim to infringement action.—(I)In general.—If an owner of the patent or the holder of the approved application under subsection (b) for the drug that is claimed by the patent or a use of which is claimed by the patent brings a patent infringement action against the applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder under subsection (b) or (c) on the ground that the patent does not claim either—(aa) the drug for which the application was approved; or(bb) an approved method of using the drug.(II)No independent cause of action.—Subclause (I) does not authorize the assertion of a claim described in subclause (I) in any civil action or proceeding other than a counterclaim described in subclause (I).
(iii)No damages.—An applicant shall not be entitled to damages in a civil action under clause (i) or a counterclaim under clause (ii).
(D)Forfeiture of 180-day exclusivity period.—
(i)Definition of forfeiture event.—In this subparagraph, the term “forfeiture event”, with respect to an application under this subsection, means the occurrence of any of the following:(I)Failure to market.—The first applicant fails to market the drug by the later of—(aa) the earlier of the date that is—(AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or(BB) 30 months after the date of submission of the application of the first applicant; or(bb) with respect to the first applicant or any other applicant (which other applicant has received tentative approval), the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred:(AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.(BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.(CC) The patent information submitted under subsection (b) or (c) is withdrawn by the holder of the application approved under subsection (b).(II)Withdrawal of application.—The first applicant withdraws the application or the Secretary considers the application to have been withdrawn as a result of a determination by the Secretary that the application does not meet the requirements for approval under paragraph (4).(III)Amendment of certification.—The first applicant amends or withdraws the certification for all of the patents with respect to which that applicant submitted a certification qualifying the applicant for the 180-day exclusivity period.(IV)Failure to obtain tentative approval.—The first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.(V)Agreement with another applicant, the listed drug application holder, or a patent owner.—The first applicant enters into an agreement with another applicant under this subsection for the drug, the holder of the application for the listed drug, or an owner of the patent that is the subject of the certification under paragraph (2)(A)(vii)(IV), the Federal Trade Commission or the Attorney General files a complaint, and there is a final decision of the Federal Trade Commission or the court with regard to the complaint from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the agreement has violated the antitrust laws (as defined in section 12 of title 15, except that the term includes section 45 of title 15 to the extent that that section applies to unfair methods of competition).(VI)Expiration of all patents.—All of the patents as to which the applicant submitted a certification qualifying it for the 180-day exclusivity period have expired.
(ii)Forfeiture.—The 180-day exclusivity period described in subparagraph (B)(iv) shall be forfeited by a first applicant if a forfeiture event occurs with respect to that first applicant.
(iii)Subsequent applicant.—If all first applicants forfeit the 180-day exclusivity period under clause (ii)—(I) approval of any application containing a certification described in paragraph (2)(A)(vii)(IV) shall be made effective in accordance with subparagraph (B)(iii); and(II) no applicant shall be eligible for a 180-day exclusivity period.
(iv)Special forfeiture rule for competitive generic therapy.—The 180-day exclusivity period described in subparagraph (B)(v) shall be forfeited by a first approved applicant if the applicant fails to market the competitive generic therapy within 75 days after the date on which the approval of the first approved applicant’s application for the competitive generic therapy is made effective.
(E) If the Secretary decides to disapprove an application, the Secretary shall give the applicant notice of an opportunity for a hearing before the Secretary on the question of whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary’s order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(F)
(i) Repealed. Pub. L. 117–9, § 1(b)(1)(B), Apr. 23, 2021, 135 Stat. 258.
(ii) If an application submitted under subsection (b) for a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under subsection (b), is approved after September 24, 1984, no application may be submitted under this subsection which refers to the drug for which the subsection (b) application was submitted before the expiration of five years from the date of the approval of the application under subsection (b), except that such an application may be submitted under this subsection after the expiration of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in subclause (IV) of paragraph (2)(A)(vii). The approval of such an application shall be made effective in accordance with subparagraph (B) except that, if an action for patent infringement is commenced during the one-year period beginning forty-eight months after the date of the approval of the subsection (b) application, the thirty-month period referred to in subparagraph (B)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(iii) If an application submitted under subsection (b) for a drug, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) that has been approved in another application approved under subsection (b), is approved after September 24, 1984, and if such application contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under this subsection for the conditions of approval of such drug in the subsection (b) application effective before the expiration of three years from the date of the approval of the application under subsection (b) for such drug.
(iv) If a supplement to an application approved under subsection (b) is approved after September 24, 1984, and the supplement contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under this subsection for a change approved in the supplement effective before the expiration of three years from the date of the approval of the supplement under subsection (b).
(v) If an application (or supplement to an application) submitted under subsection (b) for a drug, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) that has been approved in another application under subsection (b), was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (b) application was submitted or which refers to a change approved in a supplement to the subsection (b) application effective before the expiration of two years from
(6) If a drug approved under this subsection refers in its approved application to a drug the approval of which was withdrawn or suspended for grounds described in the first sentence of subsection (e) or was withdrawn or suspended under this paragraph or which, as determined by the Secretary, has been withdrawn from sale for safety or effectiveness reasons, the approval of the drug under this subsection shall be withdrawn or suspended—
(A) for the same period as the withdrawal or suspension under subsection (e) or this paragraph, or
(B) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
(7)
(A)
(i) Within sixty days of September 24, 1984, the Secretary shall publish and make available to the public—(I) a list in alphabetical order of the official and proprietary name of each drug which has been approved for safety and effectiveness under subsection (c) before September 24, 1984;(II) the date of approval if the drug is approved after 1981 and the number of the application which was approved; and(III) whether in vitro or in vivo bioequivalence studies, or both such studies, are required for applications filed under this subsection which will refer to the drug published.
(ii) Every thirty days after the publication of the first list under clause (i) the Secretary shall revise the list to include each drug which has been approved for safety and effectiveness under subsection (c) or approved under this subsection during the thirty-day period.
(iii) When patent information submitted under subsection (c) respecting a drug included on the list is to be published by the Secretary, the Secretary shall, in revisions made under clause (ii), include such information for such drug.
(iv) For each drug included on the list, the Secretary shall specify any exclusivity period that is applicable, for which the Secretary has determined the expiration date, and for which such period has not yet expired, under—(I) clause (ii), (iii), or (iv) of subsection (c)(3)(E);(II) clause (iv) or (v) of paragraph (5)(B);(III) clause (ii), (iii), or (iv) of paragraph (5)(F);(IV)section 355a of this title;(V)section 355f of this title;(VI)section 360cc(a) of this title; or(VII) subsection (u).
(v)(I) With respect to an application submitted pursuant to subsection (b)(2) for a drug that is subject to section 353(b) of this title for which the sole difference from a listed drug relied upon in the application is a difference in inactive ingredients not permitted under clause (iii) or (iv) of section 314.94(a)(9) of title 21, Code of Federal Regulations (or any successor regulations), the Secretary shall make an evaluation with respect to whether such drug is a therapeutic equivalent (as defined in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) to another approved drug product in the prescription drug product section of the list under this paragraph as follows:(aa) With respect to such an application submitted after December 29, 2022, the evaluation shall be made with respect to a listed drug relied upon in the application pursuant to subsection (b)(2) that is a pharmaceutical equivalent (as defined in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) to the drug in the application pursuant to subsection (b)(2) at the time of approval of such application or not later than 180 days after the date of such approval, provided that the request for such an evaluation is made in the original application (or in a resubmission to a complete response letter), and all necessary data and information are submitted in the original application (or in a resubmission in response to a complete response letter) for the therapeutic equivalence evaluation, including information to demonstrate bioequivalence, in a form and manner prescribed by the Secretary.(bb) With respect to such an application approved prior to or on December 29, 2022, the evaluation shall be made not later than 180 days after receipt of a request for a therapeutic equivalence evaluation submitted as part of a supplement to such application; or with respect to an application that was submitted prior to December 29, 2022, but not approved as of December 29, 2022, the evaluation shall be made not later than 180 days after the date of approval of such application if a request for such evaluation is submitted as an amendment to the application, provided that—(AA) such request for a therapeutic equivalence evaluation is being sought with respect to a listed drug relied upon in the application, and the relied upon listed drug is in the prescription drug product section of the list under this paragraph and is a pharmaceutical equivalent (as defined in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) to the drug for which a therapeutic equivalence evaluation is sought; and(BB) the amendment or supplement, as applicable, containing such request, or the relevant application, includes all necessary data and information for the therapeutic equivalence evaluation, including information to demonstrate bioequivalence, in a form and manner prescribed by the Secretary.(II) When the Secretary makes an evaluation under subclause (I), the Secretary shall, in revisions made to the list pursuant to clause (ii), include such information for such drug.
(B) A drug approved for safety and effectiveness under subsection (c) or approved under this subsection shall, for purposes of this subsection, be considered to have been published under subparagraph (A) on the date of its approval or September 24, 1984, which­ever is later.
(C) If the approval of a drug was withdrawn or suspended for grounds described in the first sentence of subsection (e) or was withdrawn or suspended under paragraph (6) or if the Secretary determines that a drug has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under subparagraph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list—
(i) for the same period as the withdrawal or suspension under subsection (e) or paragraph (6), or
(ii) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
A notice of the removal shall be published in the Federal Register.
(D) In the case of a listed drug for which the list under subparagraph (A)(i) includes a patent for such drug, and any claim of the patent has been cancelled or invalidated pursuant to a final decision issued by the Patent Trial and Appeal Board of the United States Patent and Trademark Office or by a court, from which no appeal has been, or can be, taken, if the holder of the applicable application approved under subsection (c) determines that a patent for such drug, or any patent information for such drug, no longer meets the listing requirements under this section—
(i) the holder of such approved application shall notify the Secretary, in writing, within 14 days of such decision of such cancellation or invalidation and request that such patent or patent information, as applicable, be amended or withdrawn in accordance with the decision issued by the Patent Trial and Appeal Board or a court;
(ii) the holder of such approved application shall include in any notification under clause (i) information related to such patent cancellation or invalidation decision and submit such information, including a copy of such decision, to the Secretary; and
(iii) the Secretary shall, in response to a notification under clause (i), amend or remove patent or patent information in accordance with the relevant decision from the Patent Trial and Appeals Board or court, as applicable, except that the Secretary shall not remove from the list any patent or patent information before the expiration of any 180-day exclusivity period under paragraph (5)(B)(iv) that relies on a certification described in paragraph (2)(A)(vii)(IV).
(8) For purposes of this subsection:
(A)
(i) The term “bioavailability” means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a drug and becomes available at the site of drug action.
(ii) For a drug that is not intended to be absorbed into the bloodstream, the Secretary may assess bioavailability by scientifically valid measurements intended to reflect the rate and extent to which the active ingredient or therapeutic ingredient becomes available at the site of drug action.
(B) A drug shall be considered to be bio­equivalent to a listed drug if—
(i) the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses; or
(ii) the extent of absorption of the drug does not show a significant difference from the extent of absorption of the listed drug when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses and the difference from the listed drug in the rate of absorption of the drug is intentional, is reflected in its proposed labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is considered medically insignificant for the drug.
(C) For a drug that is not intended to be absorbed into the bloodstream, the Secretary may establish alternative, scientifically valid methods to show bioequivalence if the alternative methods are expected to detect a significant difference between the drug and the listed drug in safety and therapeutic effect.
(9) The Secretary shall, with respect to each application submitted under this subsection, maintain a record of—
(A) the name of the applicant,
(B) the name of the drug covered by the application,
(C) the name of each person to whom the review of the chemistry of the application was assigned and the date of such assignment, and
(D) the name of each person to whom the bioequivalence review for such application was assigned and the date of such assignment.
The information the Secretary is required to maintain under this paragraph with respect to an application submitted under this subsection shall be made available to the public after the approval of such application.
(10)
(A) If the proposed labeling of a drug that is the subject of an application under this subsection differs from the listed drug due to a labeling revision described under clause (i), the drug that is the subject of such application shall, notwithstanding any other provision of this chapter, be eligible for approval and shall not be considered misbranded under section 352 of this title if—
(i) a revision to the labeling of the listed drug has been approved by the Secretary within 90 days of when the application is otherwise eligible for approval under this subsection;
(ii) the sponsor of the application agrees to submit revised labeling for the drug that is the subject of the application not later than 60 days after approval under this subsection of the application;
(iii) the labeling revision described under clause (i) does not include a change to the “Warnings” section of the labeling; and
(iv) such application otherwise meets the applicable requirements for approval under this subsection.
(B) If, after a labeling revision described in subparagraph (A)(i), the Secretary determines that the continued presence in interstate commerce of the labeling of the listed drug (as in effect before the revision described in subparagraph (A)(i)) adversely impacts the safe use of the drug, no application under this subsection shall be eligible for approval with such labeling.
(11)
(A) Subject to subparagraph (B), the Secretary shall prioritize the review of, and act within 8 months of the date of the submission of, an original abbreviated new drug application submitted for review under this subsection that is for a drug—
(i) for which there are not more than 3 approved drug products listed under paragraph (7) and for which there are no blocking patents and exclusivities; or
(ii) that has been included on the list under section 356e of this title.
(B) To qualify for priority review under this paragraph, not later than 60 days prior to the submission of an application described in subparagraph (A) or that the Secretary may prioritize pursuant to subparagraph (D), the applicant shall provide complete, accurate information regarding facilities involved in manufacturing processes and testing of the drug that is the subject of the application, including facilities in corresponding Type II active pharmaceutical ingredients drug master files referenced in an application and sites or organizations involved in bioequivalence and clinical studies used to support the application, to enable the Secretary to make a determination regarding whether an inspection of a facility is necessary. Such information shall include the relevant (as determined by the Secretary) sections of such application, which shall be unchanged relative to the date of the submission of such application, except to the extent that a change is made to such information to exclude a facility that was not used to generate data to meet any application requirements for such submission and that is not the only facility intended to conduct one or more unit operations in commercial production. Information provided by an applicant under this subparagraph shall not be considered the submission of an application under this subsection.
(C) The Secretary may expedite an inspection or reinspection under section 374 of this title of an establishment that proposes to manufacture a drug described in subparagraph (A).
(D) Nothing in this paragraph shall prevent the Secretary from prioritizing the review of other applications as the Secretary determines appropriate.
(12) The Secretary shall publish on the internet website of the Food and Drug Administration, and update at least once every 6 months, a list of all drugs approved under subsection (c) for which all patents and periods of exclusivity under this chapter have expired and for which no application has been approved under this subsection.
(13) Upon the request of an applicant regarding one or more specified pending applications under this subsection, the Secretary shall, as appropriate, provide review status updates indicating the categorical status of the applications by each relevant review discipline.
(k) Records and reports; required information; regulations and orders; access to records
(1) In the case of any drug for which an approval of an application filed under subsection (b) or (j) is in effect, the applicant shall establish and maintain such records, and make such reports to the Secretary, of data relating to clinical experience and other data or information, received or otherwise obtained by such applicant with respect to such drug, as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e). Regulations and orders issued under this subsection and under subsection (i) shall have due regard for the professional ethics of the medical profession and the interests of patients and shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom such regulations or orders are applicable, of similar information received or otherwise obtained by the Secretary.
(2) Every person required under this section to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(3)Active postmarket risk identification.—
(A)Definition.—In this paragraph, the term “data” refers to information with respect to a drug approved under this section or under section 262 of title 42, including claims data, patient survey data, standardized analytic files that allow for the pooling and analysis of data from disparate data environments, and any other data deemed appropriate by the Secretary.
(B)Development of postmarket risk identification and analysis methods.—The Secretary shall, not later than 2 years after September 27, 2007, in collaboration with public, academic, and private entities—
(i) develop methods to obtain access to disparate data sources including the data sources specified in subparagraph (C);
(ii) develop validated methods for the establishment of a postmarket risk identification and analysis system to link and analyze safety data from multiple sources, with the goals of including, in aggregate—(I) at least 25,000,000 patients by July 1, 2010; and(II) at least 100,000,000 patients by July 1, 2012; and
(iii) convene a committee of experts, including individuals who are recognized in the field of protecting data privacy and security, to make recommendations to the Secretary on the development of tools and methods for the ethical and scientific uses for, and communication of, postmarketing data specified under subparagraph (C), including recommendations on the development of effective research methods for the study of drug safety questions.
(C)Establishment of the postmarket risk identification and analysis system.—
(i)In general.—The Secretary shall, not later than 1 year after the development of the risk identification and analysis methods under subparagraph (B), establish and maintain procedures—(I) for risk identification and analysis based on electronic health data, in compliance with the regulations promulgated under section 264(c) of the Health Insurance Portability and Accountability Act of 1996, and in a manner that does not disclose individually identifiable health information in violation of paragraph (4)(B);(II) for the reporting (in a standardized form) of data on all serious adverse drug experiences (as defined in section 355–1(b) of this title) submitted to the Secretary under paragraph (1), and those adverse events submitted by patients, providers, and drug sponsors, when appropriate;(III) to provide for active adverse event surveillance using the following data sources, as available:(aa) Federal health-related electronic data (such as data from the Medicare program and the health systems of the Department of Veterans Affairs);(bb) private sector health-related electronic data (such as pharmaceutical purchase data and health insurance claims data); and(cc) other data as the Secretary deems necessary to create a robust system to identify adverse events and potential drug safety signals;(IV) to identify certain trends and patterns with respect to data accessed by the system;(V) to provide regular reports to the Secretary concerning adverse event trends, adverse event patterns, incidence and prevalence of adverse events, and other information the Secretary determines appropriate, which may include data on comparative national adverse event trends; and(VI) to enable the program to export data in a form appropriate for further aggregation, statistical analysis, and reporting.
(ii)Timeliness of reporting.—The procedures established under clause (i) shall ensure that such data are accessed, analyzed, and reported in a timely, routine, and systematic manner, taking into consideration the need for data completeness, coding, cleansing, and standardized analysis and transmission.
(iii)Private sector resources.—To ensure the establishment of the active postmarket risk identification and analysis system under this subsection not later than 1 year after the development of the risk identification and analysis methods under subparagraph (B), as required under clause (i), the Secretary may, on a temporary or permanent basis, implement systems or products developed by private entities.
(iv)Complementary approaches.—To the extent the active postmarket risk identification and analysis system under this subsection is not sufficient to gather data and information relevant to a priority drug safety question, the Secretary shall develop, support, and participate in complementary approaches to gather and analyze such data and information, including—(I) approaches that are complementary with respect to assessing the safety of use of a drug in domestic populations not included, or underrepresented, in the trials used to approve the drug (such as older people, people with comorbidities, pregnant women, or children); and(II) existing approaches such as the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink or successor databases.
(v)Authority for contracts.—The Secretary may enter into contracts with public and private entities to fulfill the requirements of this subparagraph.
(4)Advanced analysis of drug safety data.—
(A)Purpose.—The Secretary shall establish collaborations with public, academic, and private entities, which may include the Centers for Education and Research on Therapeutics under section 299b–1 of title 42, to provide for advanced analysis of drug safety data described in paragraph (3)(C) and other information that is publicly available or is provided by the Secretary, in order to—
(i) improve the quality and efficiency of postmarket drug safety risk-benefit analysis;
(ii) provide the Secretary with routine access to outside expertise to study advanced drug safety questions; and
(iii) enhance the ability of the Secretary to make timely assessments based on drug safety data.
(B)Privacy.—Such analysis shall not disclose individually identifiable health information when presenting such drug safety signals and trends or when responding to inquiries regarding such drug safety signals and trends.
(C)Public process for priority questions.—At least biannually, the Secretary shall seek recommendations from the Drug Safety and Risk Management Advisory Committee (or any successor committee) and from other advisory committees, as appropriate, to the Food and Drug Administration on—
(i) priority drug safety questions; and
(ii) mechanisms for answering such questions, including through—(I) active risk identification under paragraph (3); and(II) when such risk identification is not sufficient, postapproval studies and clinical trials under subsection (o)(3).
(D)Procedures for the development of drug safety collaborations.—
(i)In general.—Not later than 180 days after the date of the establishment of the active postmarket risk identification and analysis system under this subsection, the Secretary shall establish and implement procedures under which the Secretary may routinely contract with one or more qualified entities to—(I) classify, analyze, or aggregate data described in paragraph (3)(C) and information that is publicly available or is provided by the Secretary;(II) allow for prompt investigation of priority drug safety questions, including—(aa) unresolved safety questions for drugs or classes of drugs; and(bb) for a newly-approved drugs,2
2 So in original. Probably should be “drug,”.
safety signals from clinical trials used to approve the drug and other preapproval trials; rare, serious drug side effects; and the safety of use in domestic populations not included, or underrepresented, in the trials used to approve the drug (such as older people, people with comorbidities, pregnant women, or children);(III) perform advanced research and analysis on identified drug safety risks;(IV) focus postapproval studies and clinical trials under subsection (o)(3) more effectively on cases for which reports under paragraph (1) and other safety signal detection is not sufficient to resolve whether there is an elevated risk of a serious adverse event associated with the use of a drug; and(V) carry out other activities as the Secretary deems necessary to carry out the purposes of this paragraph.
(ii)Request for specific methodology.—The procedures described in clause (i) shall permit the Secretary to request that a specific methodology be used by the qualified entity. The qualified entity shall work with the Secretary to finalize the methodology to be used.
(E)Use of analyses.—The Secretary shall provide the analyses described in this paragraph, including the methods and results of such analyses, about a drug to the sponsor or sponsors of such drug.
(F)Qualified entities.—
(i)In general.—The Secretary shall enter into contracts with a sufficient number of qualified entities to develop and provide information to the Secretary in a timely manner.
(ii)Qualification.—The Secretary shall enter into a contract with an entity under clause (i) only if the Secretary determines that the entity has a significant presence in the United States and has one or more of the following qualifications:(I) The research, statistical, epidemiologic, or clinical capability and expertise to conduct and complete the activities under this paragraph, including the capability and expertise to provide the Secretary de-identified data consistent with the requirements of this subsection.(II) An information technology infrastructure in place to support electronic data and operational standards to provide security for such data.(III) Experience with, and expertise on, the development of drug safety and effectiveness research using electronic population data.(IV) An understanding of drug development or risk/benefit balancing in a clinical setting.(V) Other expertise which the Secretary deems necessary to fulfill the activities under this paragraph.
(G)Contract requirements.—Each contract with a qualified entity under subparagraph (F)(i) shall contain the following requirements:
(i)Ensuring privacy.—The qualified entity shall ensure that the entity will not use data under this subsection in a manner that—(I) violates the regulations promulgated under section 264(c) of the Health Insurance Portability and Accountability Act of 1996;(II) violates sections 552 or 552a of title 5 with regard to the privacy of individually-identifiable beneficiary health information; or(III) discloses individually identifiable health information when presenting drug safety signals and trends or when responding to inquiries regarding drug safety signals and trends.
Nothing in this clause prohibits lawful disclosure for other purposes.
(ii)Component of another organization.—If a qualified entity is a component of another organization—(I) the qualified entity shall establish appropriate security measures to maintain the confidentiality and privacy of such data; and(II) the entity shall not make an unauthorized disclosure of such data to the other components of the organization in breach of such confidentiality and privacy requirement.
(iii)Termination or nonrenewal.—If a contract with a qualified entity under this subparagraph is terminated or not renewed, the following requirements shall apply:(I)Confidentiality and privacy protections.—The entity shall continue to comply with the confidentiality and privacy requirements under this paragraph with respect to all data disclosed to the entity.(II)Disposition of data.—The entity shall return any data disclosed to such entity under this subsection to which it would not otherwise have access or, if returning the data is not practicable, destroy the data.
(H)Competitive procedures.—The Secretary shall use competitive procedures (as defined in section 132 of title 41) to enter into contracts under subparagraph (G).
(I)Review of contract in the event of a merger or acquisition.—The Secretary shall review the contract with a qualified entity under this paragraph in the event of a merger or acquisition of the entity in order to ensure that the requirements under this paragraph will continue to be met.
(J)Coordination.—In carrying out this paragraph, the Secretary shall provide for appropriate communications to the public, scientific, public health, and medical communities, and other key stakeholders, and to the extent practicable shall coordinate with the activities of private entities, professional associations, or other entities that may have sources of drug safety data.
(5) The Secretary shall—
(A) conduct regular screenings of the Adverse Event Reporting System database and post a quarterly report on the Adverse Event Reporting System Web site of any new safety information or potential signal of a serious risk identified by Adverse 3
3 So in original. Probably should be preceded by “the”.
Event Reporting System within the last quarter; and 4
4 So in original. The word “and” probably should not appear.
(B) on an annual basis, review the entire backlog of postmarket safety commitments to determine which commitments require revision or should be eliminated, report to the Congress on these determinations, and assign start dates and estimated completion dates for such commitments; and
(C) make available on the Internet website of the Food and Drug Administration—
(i) guidelines, developed with input from experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, that detail best practices for drug safety surveillance using the Adverse Event Reporting System; and
(ii) criteria for public posting of adverse event signals.
(l) Public disclosure of safety and effectiveness data and action package
(1) Safety and effectiveness data and information which has been submitted in an application under subsection (b) for a drug and which has not previously been disclosed to the public shall be made available to the public, upon request, unless extraordinary circumstances are shown—
(A) if no work is being or will be undertaken to have the application approved,
(B) if the Secretary has determined that the application is not approvable and all legal appeals have been exhausted,
(C) if approval of the application under subsection (c) is withdrawn and all legal appeals have been exhausted,
(D) if the Secretary has determined that such drug is not a new drug, or
(E) upon the effective date of the approval of the first application under subsection (j) which refers to such drug or upon the date upon which the approval of an application under subsection (j) which refers to such drug could be made effective if such an application had been submitted.
(2)Action Package for Approval.—
(A)Action package.—The Secretary shall publish the action package for approval of an application under subsection (b) or section 262 of title 42 on the Internet Web site of the Food and Drug Administration—
(i) not later than 30 days after the date of approval of such applications—(I) for a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under this section; or(II) for a biological product, no active ingredient of which has been approved in any other application under section 262 of title 42; and
(ii) not later than 30 days after the third request for such action package for approval received under section 552 of title 5 for any other drug or biological product.
(B)Immediate publication of summary review.—Notwithstanding subparagraph (A), the Secretary shall publish, on the Internet Web site of the Food and Drug Administration, the materials described in subparagraph (C)(iv) not later than 48 hours after the date of approval of the drug, except where such materials require redaction by the Secretary.
(C)Contents.—An action package for approval of an application under subparagraph (A) shall be dated and shall include the following:
(i) Documents generated by the Food and Drug Administration related to review of the application.
(ii) Documents pertaining to the format and span of the application generated during drug development.
(iii) Labeling submitted by the applicant.
(iv) A summary review that documents conclusions from all reviewing disciplines about the drug, noting any critical issues and disagreements with the applicant and within the review team and how they were resolved, recommendations for action, and an explanation of any nonconcurrence with review conclusions.
(v) The Division Director and Office Director’s decision document which includes—(I) a brief statement of concurrence with the summary review;(II) a separate review or addendum to the review if disagreeing with the summary review; and(III) a separate review or addendum to the review to add further analysis.
(vi) Identification by name of each officer or employee of the Food and Drug Administration who—(I) participated in the decision to approve the application; and(II) consents to have his or her name included in the package.
(D)Review.—A scientific review of an application is considered the work of the reviewer and shall not be altered by management or the reviewer once final.
(E)Confidential information.—This paragraph does not authorize the disclosure of any trade secret, confidential commercial or financial information, or other matter listed in section 552(b) of title 5.
(m) “Patent” defined
(n) Scientific advisory panels
(1) For the purpose of providing expert scientific advice and recommendations to the Secretary regarding a clinical investigation of a drug or the approval for marketing of a drug under this section or section 262 of title 42, the Secretary shall establish panels of experts or use panels of experts established before November 21, 1997, or both.
(2) The Secretary may delegate the appointment and oversight authority granted under section 394 of this title to a director of a center or successor entity within the Food and Drug Administration.
(3) The Secretary shall make appointments to each panel established under paragraph (1) so that each panel shall consist of—
(A) members who are qualified by training and experience to evaluate the safety and effectiveness of the drugs to be referred to the panel and who, to the extent feasible, possess skill and experience in the development, manufacture, or utilization of such drugs;
(B) members with diverse expertise in such fields  as  clinical  and  administrative  medicine, pharmacy, pharmacology, pharmacoeconomics, biological and physical sciences, and other related professions;
(C) a representative of consumer interests, and a representative of interests of the drug manufacturing industry not directly affected by the matter to be brought before the panel; and
(D) two or more members who are specialists or have other expertise in the particular disease or condition for which the drug under review is proposed to be indicated.
Scientific, trade, and consumer organizations shall be afforded an opportunity to nominate individuals for appointment to the panels. No individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter may be a voting member of any panel. The Secretary shall designate one of the members of each panel to serve as chairman thereof.
(4) The Secretary shall, as appropriate, provide education and training to each new panel member before such member participates in a panel’s activities, including education regarding requirements under this chapter and related regulations of the Secretary, and the administrative processes and procedures related to panel meetings.
(5) Panel members (other than officers or employees of the United States), while attending meetings or conferences of a panel or otherwise engaged in its business, shall be entitled to receive compensation for each day so engaged, including traveltime, at rates to be fixed by the Secretary, but not to exceed the daily equivalent of the rate in effect for positions classified above grade GS–15 of the General Schedule. While serving away from their homes or regular places of business, panel members may be allowed travel expenses (including per diem in lieu of subsistence) as authorized by section 5703 of title 5, for persons in the Government service employed intermittently.
(6) The Secretary shall ensure that scientific advisory panels meet regularly and at appropriate intervals so that any matter to be reviewed by such a panel can be presented to the panel not more than 60 days after the matter is ready for such review. Meetings of the panel may be held using electronic communication to convene the meetings.
(7) Within 90 days after a scientific advisory panel makes recommendations on any matter under its review, the Food and Drug Administration official responsible for the matter shall review the conclusions and recommendations of the panel, and notify the affected persons of the final decision on the matter, or of the reasons that no such decision has been reached. Each such final decision shall be documented including the rationale for the decision.
(o) Postmarket studies and clinical trials; labeling
(1) In general
(2) DefinitionsFor purposes of this subsection:
(A) Responsible personThe term “responsible person” means a person who—
(i) has submitted to the Secretary a covered application that is pending; or
(ii) is the holder of an approved covered application.
(B) Covered applicationThe term “covered application” means—
(i) an application under subsection (b) for a drug that is subject to section 353(b) of this title; and
(ii) an application under section 262 of title 42.
(C) New safety information; serious risk
(3) Studies and clinical trials
(A) In general
(B) Purposes of study or clinical trialThe purposes referred to in this subparagraph with respect to a postapproval study or postapproval clinical trial are the following:
(i) To assess a known serious risk related to the use of the drug involved.
(ii) To assess signals of serious risk related to the use of the drug.
(iii) To identify an unexpected serious risk when available data indicates the potential for a serious risk.
(C) Establishment of requirement after approval of covered application
(D) Determination by Secretary
(i) Postapproval studies
(ii) Postapproval clinical trials
(E) Notification; timetables; periodic reports
(i) Notification
(ii) Timetable; periodic reports
(F) Dispute resolution
(4) Safety labeling changes requested by Secretary
(A) New safety or new effectiveness information
(B) Response to notificationFollowing notification pursuant to subparagraph (A), the responsible person or the holder of the approved application under subsection (j) shall within 30 days—
(i) submit a supplement proposing changes to the approved labeling to reflect the new safety information, including changes to boxed warnings, contraindications, warnings, precautions, or adverse reactions, or new effectiveness information; or
(ii) notify the Secretary that the responsible person or the holder of the approved application under subsection (j) does not believe a labeling change is warranted and submit a statement detailing the reasons why such a change is not warranted.
(C) Review
(D) Discussions
(E) Order
(F) Dispute resolution
(G) Violation
(H) Public health threat
(I) Rule of construction
(5) Non-delegation
(p) Risk evaluation and mitigation strategy
(1) In generalA person may not introduce or deliver for introduction into interstate commerce a new drug if—
(A)
(i) the application for such drug is approved under subsection (b) or (j) and is subject to section 353(b) of this title; or
(ii) the application for such drug is approved under section 262 of title 42; and
(B) a risk evaluation and mitigation strategy is required under section 355–1 of this title with respect to the drug and the person fails to maintain compliance with the requirements of the approved strategy or with other requirements under section 355–1 of this title, including requirements regarding assessments of approved strategies.
(2) Certain postmarket studies
(q) Petitions and civil actions regarding approval of certain applications
(1) In general
(A) DeterminationThe Secretary shall not delay approval of a pending application submitted under subsection (b)(2) or (j) of this section or section 262(k) of title 42 because of any request to take any form of action relating to the application, either before or during consideration of the request, unless—
(i) the request is in writing and is a petition submitted to the Secretary pursuant to section 10.30 or 10.35 of title 21, Code of Federal Regulations (or any successor regulations); and
(ii) the Secretary determines, upon reviewing the petition, that a delay is necessary to protect the public health.
Consideration of the petition shall be separate and apart from review and approval of any application.
(B) NotificationIf the Secretary determines under subparagraph (A) that a delay is necessary with respect to an application, the Secretary shall provide to the applicant, not later than 30 days after making such determination, the following information:
(i) Notification of the fact that a determination under subparagraph (A) has been made.
(ii) If applicable, any clarification or additional data that the applicant should submit to the docket on the petition to allow the Secretary to review the petition promptly.
(iii) A brief summary of the specific substantive issues raised in the petition which form the basis of the determination.
(C) FormatThe information described in subparagraph (B) shall be conveyed via either, at the discretion of the Secretary—
(i) a document; or
(ii) a meeting with the applicant involved.
(D) Public disclosure
(E) Denial based on intent to delay
(F) Final agency actionThe Secretary shall take final agency action on a petition not later than 150 days after the date on which the petition is submitted. The Secretary shall not extend such period for any reason, including—
(i) any determination made under subparagraph (A);
(ii) the submission of comments relating to the petition or supplemental information supplied by the petitioner; or
(iii) the consent of the petitioner.
(G) Extension of 30-month period
(H) Certification
(I) Verification
(2) Exhaustion of administrative remedies
(A) Final agency action within 150 daysThe Secretary shall be considered to have taken final agency action on a petition if—
(i) during the 150-day period referred to in paragraph (1)(F), the Secretary makes a final decision within the meaning of section 10.45(d) of title 21, Code of Federal Regulations (or any successor regulation); or
(ii) such period expires without the Secretary having made such a final decision.
(B) Dismissal of certain civil actions
(C) Administrative recordFor purposes of judicial review related to the approval of an application for which a petition under paragraph (1) was submitted, the administrative record regarding any issue raised by the petition shall include—
(i) the petition filed under paragraph (1) and any supplements and comments thereto;
(ii) the Secretary’s response to such petition, if issued; and
(iii) other information, as designated by the Secretary, related to the Secretary’s determinations regarding the issues raised in such petition, as long as the information was considered by the agency no later than the date of final agency action as defined under subparagraph (2)(A), and regardless of whether the Secretary responded to the petition at or before the approval of the application at issue in the petition.
(3) Annual report on delays in approvals per petitionsThe Secretary shall annually submit to the Congress a report that specifies—
(A) the number of applications that were approved during the preceding 12-month period;
(B) the number of such applications whose effective dates were delayed by petitions referred to in paragraph (1) during such period;
(C) the number of days by which such applications were so delayed; and
(D) the number of such petitions that were submitted during such period.
(4) Exceptions
(A) This subsection does not apply to—
(i) a petition that relates solely to the timing of the approval of an application pursuant to subsection (j)(5)(B)(iv); or
(ii) a petition that is made by the sponsor of an application and that seeks only to have the Secretary take or refrain from taking any form of action with respect to that application.
(B) Paragraph (2) does not apply to a petition addressing issues concerning an application submitted pursuant to section 262(k) of title 42.
(5) Definitions
(A) Application
(B) Petition
(r) Postmarket drug safety information for patients and providers
(1) EstablishmentNot later than 1 year after September 27, 2007, the Secretary shall improve the transparency of information about drugs and allow patients and health care providers better access to information about drugs by developing and maintaining an Internet Web site that—
(A) provides links to drug safety information listed in paragraph (2) for prescription drugs that are approved under this section or licensed under section 262 of title 42; and
(B) improves communication of drug safety information to patients and providers.
(2) Internet Web siteThe Secretary shall carry out paragraph (1) by—
(A) developing and maintaining an accessible, consolidated Internet Web site with easily searchable drug safety information, including the information found on United States Government Internet Web sites, such as the United States National Library of Medicine’s Daily Med and Medline Plus Web sites, in addition to other such Web sites maintained by the Secretary;
(B) ensuring that the information provided on the Internet Web site is comprehensive and includes, when available and appropriate—
(i) patient labeling and patient packaging inserts;
(ii) a link to a list of each drug, whether approved under this section or licensed under such section 262, for which a Medication Guide, as provided for under part 208 of title 21, Code of Federal Regulations (or any successor regulations), is required;
(iii) a link to the registry and results data bank provided for under subsections (i) and (j) of section 282 of title 42;
(iv) the most recent safety information and alerts issued by the Food and Drug Administration for drugs approved by the Secretary under this section, such as product recalls, warning letters, and import alerts;
(v) publicly available information about implemented RiskMAPs and risk evaluation and mitigation strategies under subsection (o);
(vi) guidance documents and regulations related to drug safety; and
(vii) other material determined appropriate by the Secretary;
(C) providing access to summaries of the assessed and aggregated data collected from the active surveillance infrastructure under subsection (k)(3) to provide information of known and serious side-effects for drugs approved under this section or licensed under such section 262;
(D) preparing and making publicly available on the Internet website established under paragraph (1) best practices for drug safety surveillance activities for drugs approved under this section or section 262 of title 42;
(E) enabling patients, providers, and drug sponsors to submit adverse event reports through the Internet Web site;
(F) providing educational materials for patients and providers about the appropriate means of disposing of expired, damaged, or unusable medications; and
(G) supporting initiatives that the Secretary determines to be useful to fulfill the purposes of the Internet Web site.
(3) Posting of drug labeling
(4) Private sector resources
(5) Authority for contracts
(6) Review
(s) Referral to advisory committeeThe Secretary shall—
(1) refer a drug or biological product to a Food and Drug Administration advisory committee for review at a meeting of such advisory committee prior to the approval of such drug or biological if it is—
(A) a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under this section; or
(B) a biological product, no active ingredient of which has been approved in any other application under section 262 of title 42; or
(2) if the Secretary does not refer a drug or biological product described in paragraph (1) to a Food and Drug Administration advisory committee prior to such approval, provide in the action letter on the application for the drug or biological product a summary of the reasons why the Secretary did not refer the drug or biological product to an advisory committee prior to approval.
(t) Database for authorized generic drugs
(1) In general
(A) PublicationThe Commissioner shall—
(i) not later than 9 months after September 27, 2007, publish a complete list on the Internet Web site of the Food and Drug Administration of all authorized generic drugs (including drug trade name, brand company manufacturer, and the date the authorized generic drug entered the market); and
(ii) update the list quarterly to include each authorized generic drug included in an annual report submitted to the Secretary by the sponsor of a listed drug during the preceding 3-month period.
(B) Notification
(2) Inclusion
(3) Authorized generic drugIn this section, the term “authorized generic drug” means a listed drug (as that term is used in subsection (j)) that—
(A) has been approved under subsection (c); and
(B) is marketed, sold, or distributed directly or indirectly to retail class of trade under a different labeling, packaging (other than repackaging as the listed drug in blister packs, unit doses, or similar packaging for use in institutions), product code, labeler code, trade name, or trade mark than the listed drug.
(u) Certain drugs containing single enantiomers
(1) In general
(A)
(i) the single enantiomer has not been previously approved except in the approved racemic drug; and
(ii) the application submitted under subsection (b) for such non-racemic drug—(I) includes full reports of new clinical investigations (other than bioavailability studies)—(aa) necessary for the approval of the application under subsections (c) and (d); and(bb) conducted or sponsored by the applicant; and(II) does not rely on any clinical investigations (other than bioavailability studies) that are part of an application submitted under subsection (b) for approval of the approved racemic drug; and
(B) the application submitted under subsection (b) for such non-racemic drug is not submitted for approval of a condition of use—
(i) in a therapeutic category in which the approved racemic drug has been approved; or
(ii) for which any other enantiomer of the racemic drug has been approved.
(2) Limitation
(A) No approval in certain therapeutic categories
(B) Labeling
(3) Definition
(A) In general
(B) Publication by Secretary
(4) Availability
(v) Antibiotic drugs submitted before November 21, 1997
(1) Antibiotic drugs approved before November 21, 1997
(A) In general
(B) Application; antibiotic drug described
(i) Application
(ii) Antibiotic drug
(2) Antibiotic drugs submitted before November 21, 1997, but not approved
(A) In generalNotwithstanding any provision of the Food and Drug Administration Modernization Act of 1997 or any other provision of law, a sponsor of a drug that is the subject of an application described in subparagraph (B)(i) may elect to be eligible for, with respect to the drug—
(i)(I) the 3-year exclusivity period referred to under clauses (iii) and (iv) of subsection (c)(3)(E) and under clauses (iii) and (iv) of subsection (j)(5)(F), subject to the requirements of such clauses, as applicable; and(II) the 5-year exclusivity period referred to under clause (ii) of subsection (c)(3)(E) and under clause (ii) of subsection (j)(5)(F), subject to the requirements of such clauses, as applicable; or
(ii) a patent term extension under section 156 of title 35, subject to the requirements of such section.
(B) Application; antibiotic drug described
(i) Application
(ii) Antibiotic drug
(3) Limitations
(A) Exclusivities and extensions
(B) Conditions of use
(4) Application of certain provisions
(w) Deadline for determination on certain petitions
(x) Date of approval in the case of recommended controls under the CSA
(1) In general
(2) Date of approvalFor purposes of this section, with respect to an application described in paragraph (1), the term “date of approval” shall mean the later of—
(A) the date an application under subsection (b) is approved under subsection (c); or
(B) the date of issuance of the interim final rule controlling the drug.
(y) Contrast agents intended for use with applicable medical imaging devices
(1) In general
(2) Review of supplementIn reviewing a supplement submitted under this subsection, the agency center charged with the premarket review of drugs may—
(A) consult with the center charged with the premarket review of devices; and
(B) review information and data submitted to the Secretary by the sponsor of an applicable medical imaging device pursuant to section 360e, 360(k), or 360c(f)(2) of this title so long as the sponsor of such applicable medical imaging device has provided to the sponsor of the contrast agent a right of reference.
(3) DefinitionsFor purposes of this subsection—
(A) the term “new use” means a use of a contrast agent that is described in the approved labeling of an applicable medical imaging device described in section 360j(p) of this title, but that is not described in the approved labeling of the contrast agent; and
(B) the terms “applicable medical imaging device” and “contrast agent” have the meanings given such terms in section 360j(p) of this title.
(z)6
6 So in original. Two subsecs. (z) have been enacted.
Nonclinical test definedFor purposes of this section, the term “nonclinical test” means a test conducted in vitro, in silico, or in chemico, or a nonhuman in vivo test, that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug. Such test may include the following:
(1) Cell-based assays.
(2) Organ chips and microphysiological systems.
(3) Computer modeling.
(4) Other nonhuman or human biology-based test methods, such as bioprinting.
(5) Animal tests.
(z)6 Diversity action plan for clinical studies 7
7 See Delayed Applicability of Amendment note below.
(1) With respect to a clinical investigation of a new drug that is a phase 3 study, as defined in section 312.21(c) of title 21, Code of Federal Regulations (or successor regulations), or, as appropriate, another pivotal study of a new drug (other than bioavailability or bioequivalence studies), the sponsor of such drug shall submit to the Secretary a diversity action plan.
(2) Such diversity action plan shall include—
(A) the sponsor’s goals for enrollment in such clinical study;
(B) the sponsor’s rationale for such goals; and
(C) an explanation of how the sponsor intends to meet such goals.
(3) The sponsor shall submit to the Secretary such diversity action plan, in the form and manner specified by the Secretary in guidance, as soon as practicable but not later than the date on which the sponsor submits the protocol to the Secretary for such a phase 3 study or other pivotal study of the drug. The sponsor may submit modifications to the diversity action plan. Any such modifications shall be in the form and manner specified by the Secretary in guidance.
(4)
(A) On the initiative of the Secretary or at the request of a sponsor, the Secretary may waive any requirement in paragraph (1), (2), or (3) if the Secretary determines that a waiver is necessary based on what is known or what can be determined about the prevalence or incidence of the disease or condition for which the new drug is under investigation (including in terms of the patient population that may use the drug), if conducting a clinical investigation in accordance with a diversity action plan would otherwise be impracticable, or if such waiver is necessary to protect public health during a public health emergency.
(B) The Secretary shall issue a written response granting or denying a request from a sponsor for a waiver within 60 days of receiving such request.
(5) No diversity action plan shall be required for a submission described in section 360bbb of this title.
(June 25, 1938, ch. 675, § 505, 52 Stat. 1052; Pub. L. 86–507, § 1(18), June 11, 1960, 74 Stat. 201; Pub. L. 87–781, title I, §§ 102(b)–(d), 103(a), (b), 104(a)–(d)(2), Oct. 10, 1962, 76 Stat. 781–783, 784, 785; Pub. L. 92–387, § 4(d), Aug. 16, 1972, 86 Stat. 562; Pub. L. 98–417, title I, §§ 101, 102(a)–(b)(5), 103, 104, Sept. 24, 1984, 98 Stat. 1585, 1592, 1593, 1597; Pub. L. 102–282, § 5, May 13, 1992, 106 Stat. 161; Pub. L. 103–80, § 3(n), Aug. 13, 1993, 107 Stat. 777; Pub. L. 105–115, title I, §§ 115, 117, 119, 120, 124(a), Nov. 21, 1997, 111 Stat. 2313, 2315, 2316, 2318, 2324; Pub. L. 106–113, div. B, § 1000(a)(9) [title IV, § 4732(b)(11)], Nov. 29, 1999, 113 Stat. 1536, 1501A–584; Pub. L. 107–109, § 15(c)(1), Jan. 4, 2002, 115 Stat. 1420; Pub. L. 108–155, § 2(b)(1), Dec. 3, 2003, 117 Stat. 1941; Pub. L. 108–173, title XI, §§ 1101(a), (b), 1102(a), 1103(a), Dec. 8, 2003, 117 Stat. 2448, 2452, 2457, 2460; Pub. L. 110–85, title VII, § 701(b), title VIII, § 801(b)(3)(A), (B), title IX, §§ 901(a), 903, 905(a), 914(a), 915, 916, 918, 920, 921, title XI, § 1113, Sept. 27, 2007, 121 Stat. 903, 921, 922, 943, 944, 953, 957, 958, 960–962, 976; Pub. L. 110–316, title III, § 301, Aug. 14, 2008, 122 Stat. 3524; Pub. L. 110–379, § 4(a), Oct. 8, 2008, 122 Stat. 4076; Pub. L. 111–31, div. A, title I, § 103(e), June 22, 2009, 123 Stat. 1837; Pub. L. 111–148, title VII, § 7002(d)(1), title X, § 10609, Mar. 23, 2010, 124 Stat. 816, 1014; Pub. L. 112–144, title IX, § 905, title XI, §§ 1101, 1134(a), 1135, July 9, 2012, 126 Stat. 1092, 1108, 1123; Pub. L. 113–5, title III, § 301, Mar. 13, 2013, 127 Stat. 179; Pub. L. 114–89, § 2(a)(1), Nov. 25, 2015, 129 Stat. 698; Pub. L. 114–255, div. A, title III, §§ 3024(b), 3031(a), 3075(a), (b), 3101(a)(2)(B), 3102(1), Dec. 13, 2016, 130 Stat. 1099, 1138, 1152, 1156; Pub. L. 115–52, title VI, § 601, title VII, § 706(b), title VIII, §§ 801, 802, 808, title IX, § 901(a), Aug. 18, 2017, 131 Stat. 1048, 1059, 1068, 1069, 1074, 1076; Pub. L. 115–271, title III, § 3041(b), Oct. 24, 2018, 132 Stat. 3942; Pub. L. 116–290, § 2(a)–(d)(1), (g), Jan. 5, 2021, 134 Stat. 4889–4892; Pub. L. 117–9, § 1(a)(1), (b)(1), Apr. 23, 2021, 135 Stat. 256, 258; Pub. L. 117–180, div. F, title V, § 5004, Sept. 30, 2022,

CITE AS: 21 USC 355

§ 355–1. Risk evaluation and mitigation strategies
(a) Submission of proposed strategy
(1) Initial approvalIf the Secretary, in consultation with the office responsible for reviewing the drug and the office responsible for postapproval safety with respect to the drug, determines that a risk evaluation and mitigation strategy is necessary to ensure that the benefits of the drug outweigh the risks of the drug, and informs the person who submits such application of such determination, then such person shall submit to the Secretary as part of such application a proposed risk evaluation and mitigation strategy. In making such a determination, the Secretary shall consider the following factors:
(A) The estimated size of the population likely to use the drug involved.
(B) The seriousness of the disease or condition that is to be treated with the drug.
(C) The expected benefit of the drug with respect to such disease or condition.
(D) The expected or actual duration of treatment with the drug.
(E) The seriousness of any known or potential adverse events that may be related to the drug and the background incidence of such events in the population likely to use the drug.
(F) Whether the drug is a new molecular entity.
(2) Postapproval requirement
(A) In general
(B) Submission of proposed strategy
(3) Abbreviated new drug applications
(4) Non-delegation
(b) DefinitionsFor purposes of this section:
(1) Adverse drug experienceThe term “adverse drug experience” means any adverse event associated with the use of a drug in humans, whether or not considered drug related, including—
(A) an adverse event occurring in the course of the use of the drug in professional practice;
(B) an adverse event occurring from an overdose of the drug, whether accidental or intentional;
(C) an adverse event occurring from abuse of the drug;
(D) an adverse event occurring from withdrawal of the drug; and
(E) any failure of expected pharmacological action of the drug, which may include reduced effectiveness under the conditions of use prescribed in the labeling of such drug, but which may not include reduced effectiveness that is in accordance with such labeling.
(2) Covered application
(3) New safety informationThe term “new safety information”, with respect to a drug, means information derived from a clinical trial, an adverse event report, a postapproval study (including a study under section 355(o)(3) of this title), or peer-reviewed biomedical literature; data derived from the postmarket risk identification and analysis system under section 355(k) of this title; or other scientific data deemed appropriate by the Secretary about—
(A) a serious risk or an unexpected serious risk associated with use of the drug that the Secretary has become aware of (that may be based on a new analysis of existing information) since the drug was approved, since the risk evaluation and mitigation strategy was required, or since the last assessment of the approved risk evaluation and mitigation strategy for the drug; or
(B) the effectiveness of the approved risk evaluation and mitigation strategy for the drug obtained since the last assessment of such strategy.
(4) Serious adverse drug experienceThe term “serious adverse drug experience” is an adverse drug experience that—
(A) results in—
(i) death;
(ii) an adverse drug experience that places the patient at immediate risk of death from the adverse drug experience as it occurred (not including an adverse drug experience that might have caused death had it occurred in a more severe form);
(iii) inpatient hospitalization or prolongation of existing hospitalization;
(iv) a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or
(v) a congenital anomaly or birth defect; or
(B) based on appropriate medical judgment, may jeopardize the patient and may require a medical or surgical intervention to prevent an outcome described under subparagraph (A).
(5) Serious risk
(6) Signal of a serious riskThe term “signal of a serious risk” means information related to a serious adverse drug experience associated with use of a drug and derived from—
(A) a clinical trial;
(B) adverse event reports;
(C) a postapproval study, including a study under section 355(o)(3) of this title;
(D) peer-reviewed biomedical literature;
(E) data derived from the postmarket risk identification and analysis system under section 355(k)(4) of this title; or
(F) other scientific data deemed appropriate by the Secretary.
(7) Responsible person
(8) Unexpected serious risk
(c) ContentsA proposed risk evaluation and mitigation strategy under subsection (a) shall—
(1) include the timetable required under subsection (d); and
(2) to the extent required by the Secretary, in consultation with the office responsible for reviewing the drug and the office responsible for postapproval safety with respect to the drug, include additional elements described in subsections (e) and (f).
(d) Minimal strategyFor purposes of subsection (c)(1), the risk evaluation and mitigation strategy for a drug shall require a timetable for submission of assessments of the strategy that—
(1) includes an assessment, by the date that is 18 months after the strategy is initially approved;
(2) includes an assessment by the date that is 3 years after the strategy is initially approved;
(3) includes an assessment in the seventh year after the strategy is so approved; and
(4) subject to paragraphs (1), (2), and (3)—
(A) is at a frequency specified in the strategy;
(B) is increased or reduced in frequency as necessary as provided for in subsection (g)(4)(A); and
(C) is eliminated after the 3-year period described in paragraph (1) if the Secretary determines that serious risks of the drug have been adequately identified and assessed and are being adequately managed.
(e) Additional potential elements of strategy
(1) In general
(2) Medication Guide; patient package insertThe risk evaluation and mitigation strategy for a drug may require that, as applicable, the responsible person develop for distribution to each patient when the drug is dispensed—
(A) a Medication Guide, as provided for under part 208 of title 21, Code of Federal Regulations (or any successor regulations); and
(B) a patient package insert, if the Secretary determines that such insert may help mitigate a serious risk of the drug.
(3) Communication planThe risk evaluation and mitigation strategy for a drug may require that the responsible person conduct a communication plan to health care providers, if, with respect to such drug, the Secretary determines that such plan may support implementation of an element of the strategy (including under this paragraph). Such plan may include—
(A) sending letters to health care providers;
(B) disseminating information about the elements of the risk evaluation and mitigation strategy to encourage implementation by health care providers of components that apply to such health care providers, or to explain certain safety protocols (such as medical monitoring by periodic laboratory tests) 1
1 So in original. Probably should be followed by a semicolon.
(C) disseminating information to health care providers through professional societies about any serious risks of the drug and any protocol to assure safe use; or
(D) disseminating information to health care providers about drug formulations or properties, including information about the limitations or patient care implications of such formulations or properties, and how such formulations or properties may be related to serious adverse drug events associated with use of the drug.
(4) Packaging and disposalThe Secretary may require a risk evaluation mitigation strategy for a drug for which there is a serious risk of an adverse drug experience described in subparagraph (B) or (C) of subsection (b)(1), taking into consideration the factors described in subparagraphs (C) and (D) of subsection (f)(2) and in consultation with other relevant Federal agencies with authorities over drug disposal packaging, which may include requiring that—
(A) the drug be made available for dispensing to certain patients in unit dose packaging, packaging that provides a set duration, or another packaging system that the Secretary determines may mitigate such serious risk; or
(B) the drug be dispensed to certain patients with a safe disposal packaging or safe disposal system if the Secretary determines that such safe disposal packaging or system may mitigate such serious risk and is sufficiently available.
(f) Providing safe access for patients to drugs with known serious risks that would otherwise be unavailable
(1) Allowing safe access to drugs with known serious risks
(A) the drug, which has been shown to be effective, but is associated with a serious adverse drug experience, can be approved only if, or would be withdrawn unless, such elements are required as part of such strategy to mitigate a specific serious risk listed in the labeling of the drug; and
(B) for a drug initially approved without elements to assure safe use, other elements under subsections (c), (d), and (e) are not sufficient to mitigate such serious risk.
(2) Assuring access and minimizing burdenSuch elements to assure safe use under paragraph (1) shall—
(A) be commensurate with the specific serious risk listed in the labeling of the drug;
(B) within 30 days of the date on which any element under paragraph (1) is imposed, be posted publicly by the Secretary with an explanation of how such elements will mitigate the observed safety risk;
(C) considering such risk, not be unduly burdensome on patient access to the drug, considering in particular—
(i) patients with serious or life-threatening diseases or conditions;
(ii) patients who have difficulty accessing health care (such as patients in rural or medically underserved areas); and
(iii) patients with functional limitations; and
(D) to the extent practicable, so as to minimize the burden on the health care delivery system—
(i) conform with elements to assure safe use for other drugs with similar, serious risks; and
(ii) be designed to be compatible with established distribution, procurement, and dispensing systems for drugs.
(3) Elements to assure safe useThe elements to assure safe use under paragraph (1) shall include 1 or more goals to mitigate a specific serious risk listed in the labeling of the drug and, to mitigate such risk, may require that—
(A) health care providers who prescribe the drug have particular training or experience, or are specially certified (the opportunity to obtain such training or certification with respect to the drug shall be available to any willing provider from a frontier area in a widely available training or certification method (including an on-line course or via mail) as approved by the Secretary at reasonable cost to the provider);
(B) pharmacies, practitioners, or health care settings that dispense the drug are specially certified (the opportunity to obtain such certification shall be available to any willing provider from a frontier area);
(C) the drug be dispensed to patients only in certain health care settings, such as hospitals;
(D) the drug be dispensed to patients with evidence or other documentation of safe-use conditions, such as laboratory test results;
(E) each patient using the drug be subject to certain monitoring; or
(F) each patient using the drug be enrolled in a registry.
(4) Implementation systemThe elements to assure safe use under paragraph (1) that are described in subparagraphs (B), (C), and (D) of paragraph (3) may include a system through which the applicant is able to take reasonable steps to—
(A) monitor and evaluate implementation of such elements by health care providers, pharmacists, and other parties in the health care system who are responsible for implementing such elements; and
(B) work to improve implementation of such elements by such persons.
(5) Evaluation of elements to assure safe useThe Secretary, through the Drug Safety and Risk Management Advisory Committee (or successor committee) or other advisory committee of the Food and Drug Administration, shall—
(A) seek input from patients, physicians, pharmacists, and other health care providers about how elements to assure safe use under this subsection for 1 or more drugs may be standardized so as not to be—
(i) unduly burdensome on patient access to the drug; and
(ii) to the extent practicable, minimize 2
2 So in original. Does not follow from introductory provisions.
the burden on the health care delivery system;
(B) periodically evaluate, for 1 or more drugs, the elements to assure safe use of such drug to assess whether the elements—
(i) assure safe use of the drug;
(ii) are not unduly burdensome on patient access to the drug; and
(iii) to the extent practicable, minimize the burden on the health care delivery system; and
(C) considering such input and evaluations—
(i) issue or modify agency guidance about how to implement the requirements of this subsection; and
(ii) modify elements under this subsection for 1 or more drugs as appropriate.
(6) Additional mechanisms to assure access
(7) Repealed. Pub. L. 113–5, title III, § 302(c)(1), Mar. 13, 2013, 127 Stat. 185
(8) Limitation
(g) Assessment and modification of approved strategy
(1) Voluntary assessments
(2) Required assessmentsA responsible person shall submit an assessment of the approved risk evaluation and mitigation strategy for a drug—
(A) when submitting a supplemental application for a new indication for use under section 355(b) of this title or under section 262 of title 42, unless the drug is not subject to section 353(b) of this title and the risk evaluation and mitigation strategy for the drug includes only the timetable under subsection (d);
(B) when required by the strategy, as provided for in such timetable under subsection (d);
(C) within a time period to be determined by the Secretary, if the Secretary, in consultation with the offices described in subsection (c)(2), determines that an assessment is needed to evaluate whether the approved strategy should be modified to—
(i) ensure the benefits of the drug outweigh the risks of the drug; or
(ii) minimize the burden on the health care delivery system of complying with the strategy.
(3) Requirements for assessments
(4) Modification
(A) On initiative of responsible person
(B) On initiative of SecretaryAfter the approval of a risk evaluation and mitigation strategy by the Secretary, the Secretary may, at any time, require a responsible person to submit a proposed modification to the strategy within 120 days or within such reasonable time as the Secretary specifies, if the Secretary, in consultation with the offices described in subsection (c)(2), determines that 1 or more goals or elements should be added, modified, or removed from the approved strategy to—
(i) ensure the benefits of the drug outweigh the risks of the drug;
(ii) minimize the burden on the health care delivery system of complying with the strategy; or
(iii) accommodate different, comparable aspects of the elements to assure safe use for a drug that is the subject of an application under section 355(j) of this title, and the applicable listed drug.
(h) Review of proposed strategies; review of assessments and modifications of approved strategies
(1) In general
(2) Action
(A) In general
(i) Timeframe
(ii) Minor modifications
(iii) REMS modification due to safety labeling changes
(iv) Guidance
(B) Inaction
(C) Public availability
(3) Dispute resolution at initial approval
(4) Dispute resolution in all other cases
(A) Request for review
(i) In general
(ii) Scheduling
(B) Scheduling reviewIf a responsible person requests review under subparagraph (A), the Secretary—
(i) shall schedule the dispute for review at 1 of the next 2 regular meetings of the Drug Safety Oversight Board, whichever meeting date is more practicable; or
(ii) may convene a special meeting of the Drug Safety Oversight Board to review the matter more promptly, including to meet an action deadline on an application (including a supplemental application).
(C) Agreement after discussion or administrative appeals
(i) Further discussion or administrative appeals
(ii) Agreement terminates dispute resolution
(D) Meeting of the BoardAt a meeting of the Drug Safety Oversight Board described in subparagraph (B), the Board shall—
(i) hear from both parties via written or oral presentation; and
(ii) review the dispute.
(E) Record of proceedings
(F) Recommendation of the Board
(G) Action by the Secretary
(i) Action letterWith respect to a proposal or assessment referred to in paragraph (1), the Secretary shall issue an action letter that resolves the dispute not later than the later of—(I) the action deadline for the action letter on the application; or(II) 7 days after receiving the recommendation of the Drug Safety Oversight Board.
(ii) Order
(H) Inaction
(I) Effect on action deadline
(J) Disqualification
(K) Additional expertise
(5) Use of advisory committeesThe Secretary may convene a meeting of 1 or more advisory committees of the Food and Drug Administration to—
(A) review a concern about the safety of a drug or class of drugs, including before an assessment of the risk evaluation and mitigation strategy or strategies of such drug or drugs is required to be submitted under subparagraph (B) or (C) of subsection (g)(2);
(B) review the risk evaluation and mitigation strategy or strategies of a drug or group of drugs; or
(C) review a dispute under paragraph (3) or (4).
(6) Process for addressing drug class effects
(A) In general
(B) NoticeIf the Secretary defers an assessment under subparagraph (A), the Secretary shall—
(i) give notice of the deferral to the holder of the approved covered application not later than 5 days after the deferral;
(ii) publish the deferral in the Federal Register; and
(iii) give notice to the public of any public meetings to be convened under subparagraph (A), including a description of the deferral.
(C) Public meetingsSuch public meetings may include—
(i) 1 or more meetings of the responsible person for such drugs;
(ii) 1 or more meetings of 1 or more advisory committees of the Food and Drug Administration, as provided for under paragraph (6); 4
4 See References in Text note below.
or
(iii) 1 or more workshops of scientific experts and other stakeholders.
(D) ActionAfter considering the discussions from any meetings under subparagraph (A), the Secretary may—
(i) announce in the Federal Register a planned regulatory action, including a modification to each risk evaluation and mitigation strategy, for drugs in the pharmacological class;
(ii) seek public comment about such action; and
(iii) after seeking such comment, issue an order addressing such regulatory action.
(7) International coordination
(8) Effect
(i) Abbreviated new drug applications
(1) In generalA drug that is the subject of an abbreviated new drug application under section 355(j) of this title is subject to only the following elements of the risk evaluation and mitigation strategy required under subsection (a) for the applicable listed drug:
(A) A Medication Guide or patient package insert, if required under subsection (e) for the applicable listed drug.
(B) A packaging or disposal requirement, if required under subsection (e)(4) for the applicable listed drug.
(C)
(i) Elements to assure safe use, if required under subsection (f) for the listed drug, which, subject to clause (ii), for a drug that is the subject of an application under section 355(j) of this title may use—(I) a single, shared system with the listed drug under subsection (f); or(II) a different, comparable aspect of the elements to assure safe use under subsection (f).
(ii) The Secretary may require a drug that is the subject of an application under section 355(j) of this title and the listed drug to use a single, shared system under subsection (f), if the Secretary determines that no different, comparable aspect of the elements to assure safe use could satisfy the requirements of subsection (f).
(2) Action by SecretaryFor an applicable listed drug for which a drug is approved under section 355(j) of this title, the Secretary—
(A) shall undertake any communication plan to health care providers required under subsection (e)(3) for the applicable listed drug;
(B) shall permit packaging systems and safe disposal packaging or safe disposal systems that are different from those required for the applicable listed drug under subsection (e)(4); and
(C) shall inform the responsible person for the drug that is so approved if the risk evaluation and mitigation strategy for the applicable listed drug is modified.
(3) Shared REMS
(j) Drug Safety Oversight Board
(1) In general
(2) Composition; meetingsThe Drug Safety Oversight Board shall—
(A) be composed of scientists and health care practitioners appointed by the Secretary, each of whom is an employee of the Federal Government;
(B) include representatives from offices throughout the Food and Drug Administration, including the offices responsible for postapproval safety of drugs;
(C) include at least 1 representative each from the National Institutes of Health and the Department of Health and Human Services (other than the Food and Drug Administration);
(D) include such representatives as the Secretary shall designate from other appropriate agencies that wish to provide representatives; and
(E) meet at least monthly to provide oversight and advice to the Secretary on the management of important drug safety issues.
(k) Waiver in public health emergenciesThe Secretary may waive any requirement of this section with respect to a qualified countermeasure (as defined in section 247d–6a(a)(2) of title 42) to which a requirement under this section has been applied, if the Secretary determines that such waiver is required to mitigate the effects of, or reduce the severity of, the circumstances under which—
(1) a determination described in subparagraph (A), (B), or (C) of section 360bbb–3(b)(1) of this title has been made by the Secretary of Homeland Security, the Secretary of Defense, or the Secretary, respectively; or
(2) the identification of a material threat described in subparagraph (D) of section 360bbb–3(b)(1) of this title has been made pursuant to section 247d–6b of title 42.
(l) Provision of samples not a violation of strategy
(m) Separate REMS
(June 25, 1938, ch. 675, § 505–1, as added Pub. L. 110–85, title IX, § 901(b), Sept. 27, 2007, 121 Stat. 926; amended Pub. L. 112–144, title XI, § 1132(a), (b), July 9, 2012, 126 Stat. 1119, 1120; Pub. L. 113–5, title III, § 302(c), Mar. 13, 2013, 127 Stat. 185; Pub. L. 114–255, div. A, title III, §§ 3075(c), 3101(a)(2)(C), Dec. 13, 2016, 130 Stat. 1139, 1153; Pub. L. 115–52, title VI, § 606, Aug. 18, 2017, 131 Stat. 1049; Pub. L. 115–271, title III, §§ 3032(a)–(c), 3041(a), Oct. 24, 2018, 132 Stat. 3940–3942; Pub. L. 116–94, div. N, title I, § 610(d), (f), Dec. 20, 2019, 133 Stat. 3135, 3136; Pub. L. 117–328, div. FF, title III, § 3221, Dec. 29, 2022, 136 Stat. 5829.)

CITE AS: 21 USC 355-1

§ 355–2. Actions for delays of generic drugs and biosimilar biological products
(a) DefinitionsIn this section—
(1) the term “commercially reasonable, market-based terms” means—
(A) a nondiscriminatory price for the sale of the covered product at or below, but not greater than, the most recent wholesale acquisition cost for the drug, as defined in section 1395w–3a(c)(6)(B) of title 42;
(B) a schedule for delivery that results in the transfer of the covered product to the eligible product developer consistent with the timing under subsection (b)(2)(A)(iv); and
(C) no additional conditions are imposed on the sale of the covered product;
(2) the term “covered product”—
(A) means—
(i) any drug approved under subsection (c) or (j) of section 355 of this title or biological product licensed under subsection (a) or (k) of section 262 of title 42;
(ii) any combination of a drug or biological product described in clause (i); or
(iii) when reasonably necessary to support approval of an application under section 355 of this title, or section 262 of title 42, as applicable, or otherwise meet the requirements for approval under either such section, any product, including any device, that is marketed or intended for use with such a drug or biological product; and
(B) does not include any drug or biological product that appears on the drug shortage list in effect under section 356e of this title, unless—
(i) the drug or biological product has been on the drug shortage list in effect under such section 356e of this title continuously for more than 6 months; or
(ii) the Secretary determines that inclusion of the drug or biological product as a covered product is likely to contribute to alleviating or preventing a shortage.
(3) the term “device” has the meaning given the term in section 321 of this title;
(4) the term “eligible product developer” means a person that seeks to develop a product for approval pursuant to an application for approval under subsection (b)(2) or (j) of section 355 of this title or for licensing pursuant to an application under section 262(k) of title 42;
(5) the term “license holder” means the holder of an application approved under subsection (c) or (j) of section 355 of this title or the holder of a license under subsection (a) or (k) of section 262 of title 42 for a covered product;
(6) the term “REMS” means a risk evaluation and mitigation strategy under section 355–1 of this title;
(7) the term “REMS with ETASU” means a REMS that contains elements to assure safe use under section 355–1(f) of this title;
(8) the term “Secretary” means the Secretary of Health and Human Services;
(9) the term “single, shared system of elements to assure safe use” means a single, shared system of elements to assure safe use under section 355–1(f) of this title; and
(10) the term “sufficient quantities” means an amount of a covered product that the eligible product developer determines allows it to—
(A) conduct testing to support an application under—
(i) subsection (b)(2) or (j) of section 355 of this title; or
(ii)section 262(k) of title 42; and
(B) fulfill any regulatory requirements relating to approval of such an application.
(b) Civil action for failure to provide sufficient quantities of a covered product
(1) In general
(2) Elements
(A) In generalTo prevail in a civil action brought under paragraph (1), an eligible product developer shall prove, by a preponderance of the evidence—
(i) that—(I) the covered product is not subject to a REMS with ETASU; or(II) if the covered product is subject to a REMS with ETASU—(aa) the eligible product developer has obtained a covered product authorization from the Secretary in accordance with subparagraph (B); and(bb) the eligible product developer has provided a copy of the covered product authorization to the license holder;
(ii) that, as of the date on which the civil action is filed, the eligible product developer has not obtained sufficient quantities of the covered product on commercially reasonable, market-based terms;
(iii) that the eligible product developer has submitted a written request to purchase sufficient quantities of the covered product to the license holder, and such request—(I) was sent to a named corporate officer of the license holder;(II) was made by certified or registered mail with return receipt requested;(III) specified an individual as the point of contact for the license holder to direct communications related to the sale of the covered product to the eligible product developer and a means for electronic and written communications with that individual; and(IV) specified an address to which the covered product was to be shipped upon reaching an agreement to transfer the covered product; and
(iv) that the license holder has not delivered to the eligible product developer sufficient quantities of the covered product on commercially reasonable, market-based terms—(I) for a covered product that is not subject to a REMS with ETASU, by the date that is 31 days after the date on which the license holder received the request for the covered product; and(II) for a covered product that is subject to a REMS with ETASU, by 31 days after the later of—(aa) the date on which the license holder received the request for the covered product; or(bb) the date on which the license holder received a copy of the covered product authorization issued by the Secretary in accordance with subparagraph (B).
(B) Authorization for covered product subject to a REMS with ETASU
(i) Request
(ii) AuthorizationNot later than 120 days after the date on which a request under clause (i) is received, the Secretary shall, by written notice, authorize the eligible product developer to obtain sufficient quantities of an individual covered product subject to a REMS with ETASU for purposes of—(I) development and testing that does not involve human clinical trials, if the eligible product developer has agreed to comply with any conditions the Secretary determines necessary; or(II) development and testing that involves human clinical trials, if the eligible product developer has—(aa)(AA) submitted protocols, informed consent documents, and informational materials for testing that include protections that provide safety protections comparable to those provided by the REMS for the covered product; or(BB) otherwise satisfied the Secretary that such protections will be provided; and(bb) met any other requirements the Secretary may establish.
(iii) Notice
(3) Affirmative defenseIn a civil action brought under paragraph (1), it shall be an affirmative defense, on which the defendant has the burden of persuasion by a preponderance of the evidence—
(A) that, on the date on which the eligible product developer requested to purchase sufficient quantities of the covered product from the license holder—
(i) neither the license holder nor any of its agents, wholesalers, or distributors was engaged in the manufacturing or commercial marketing of the covered product; and
(ii) neither the license holder nor any of its agents, wholesalers, or distributors otherwise had access to inventory of the covered product to supply to the eligible product developer on commercially reasonable, market-based terms;
(B) that—
(i) the license holder sells the covered product through agents, distributors, or wholesalers;
(ii) the license holder has placed no restrictions, explicit or implicit, on its agents, distributors, or wholesalers to sell covered products to eligible product developers; and
(iii) the covered product can be purchased by the eligible product developer in sufficient quantities on commercially reasonable, market-based terms from the agents, distributors, or wholesalers of the license holder; or
(C) that the license holder made an offer to the individual specified pursuant to paragraph (2)(A)(iii)(III), by a means of communication (electronic, written, or both) specified pursuant to such paragraph, to sell sufficient quantities of the covered product to the eligible product developer at commercially reasonable market-based terms—
(i) for a covered product that is not subject to a REMS with ETASU, by the date that is 14 days after the date on which the license holder received the request for the covered product, and the eligible product developer did not accept such offer by the date that is 7 days after the date on which the eligible product developer received such offer from the license holder; or
(ii) for a covered product that is subject to a REMS with ETASU, by the date that is 20 days after the date on which the license holder received the request for the covered product, and the eligible product developer did not accept such offer by the date that is 10 days after the date on which the eligible product developer received such offer from the license holder.
(4) Remedies
(A) In generalIf an eligible product developer prevails in a civil action brought under paragraph (1), the court shall—
(i) order the license holder to provide to the eligible product developer without delay sufficient quantities of the covered product on commercially reasonable, market-based terms;
(ii) award to the eligible product developer reasonable attorney’s fees and costs of the civil action; and
(iii) award to the eligible product developer a monetary amount sufficient to deter the license holder from failing to provide eligible product developers with sufficient quantities of a covered product on commercially reasonable, market-based terms, if the court finds, by a preponderance of the evidence—(I) that the license holder delayed providing sufficient quantities of the covered product to the eligible product developer without a legitimate business justification; or(II) that the license holder failed to comply with an order issued under clause (i).
(B) Maximum monetary amountA monetary amount awarded under subparagraph (A)(iii) shall not be greater than the revenue that the license holder earned on the covered product during the period—
(i) beginning on—(I) for a covered product that is not subject to a REMS with ETASU, the date that is 31 days after the date on which the license holder received the request; or(II) for a covered product that is subject to a REMS with ETASU, the date that is 31 days after the later of—(aa) the date on which the license holder received the request; or(bb) the date on which the license holder received a copy of the covered product authorization issued by the Secretary in accordance with paragraph (2)(B); and
(ii) ending on the date on which the eligible product developer received sufficient quantities of the covered product.
(C) Avoidance of delay
(c) Limitation of liability
(d) Omitted
(e) Rule of construction
(1) DefinitionIn this subsection, the term “antitrust laws”—
(A) has the meaning given the term in subsection (a) of section 12 of title 15; and
(B) includes section 45 of title 15 to the extent that such section applies to unfair methods of competition.
(2) Antitrust laws
(f) Omitted
(g) Rule of constructionNothing in this section, the amendments made by this section, or in section 355–1 of this title, shall be construed as—
(1) prohibiting a license holder from providing an eligible product developer access to a covered product in the absence of an authorization under this section; or
(2) in any way negating the applicability of a REMS with ETASU, as otherwise required under such section 355–1 of this title, with respect to such covered product.
(Pub. L. 116–94, div. N, title I, § 610, Dec. 20, 2019, 133 Stat. 3130.)

CITE AS: 21 USC 355-2

§ 355a. Pediatric studies of drugs
(a) Definitions
(b) Market exclusivity for new drugs
(1) In generalExcept as provided in paragraph (2), if, prior to approval of an application that is submitted under section 355(b)(1) of this title, the Secretary determines that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the Secretary makes a written request for pediatric studies (which shall include a timeframe for completing such studies), the applicant agrees to the request, such studies are completed using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and accepted in accordance with subsection (d)(4)—
(A)
(i)(I) the period referred to in subsection (c)(3)(E)(ii) of section 355 of this title, and in subsection (j)(5)(F)(ii) of such section, is deemed to be five years and six months rather than five years, and the references in subsections (c)(3)(E)(ii) and (j)(5)(F)(ii) of such section to four years, to forty-eight months, and to seven and one-half years are deemed to be four and one-half years, fifty-four months, and eight years, respectively; or(II) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(E) of such section, and in clauses (iii) and (iv) of subsection (j)(5)(F) of such section, is deemed to be three years and six months rather than three years; and
(ii) if the drug is designated under section 360bb of this title for a rare disease or condition, the period referred to in section 360cc(a) of this title is deemed to be seven years and six months rather than seven years; and
(B)
(i) if the drug is the subject of—(I) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of section 355 of this title and for which pediatric studies were submitted prior to the expiration of the patent (including any patent extensions); or(II) a listed patent for which a certification has been submitted under subsections (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 355 of this title,
the period during which an application may not be approved under section 355(c)(3) of this title or section 355(j)(5)(B) of this title shall be extended by a period of six months after the date the patent expires (including any patent extensions); or
(ii) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the patent infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed, the period during which an application may not be approved under section 355(c)(3) of this title or section 355(j)(5)(B) of this title shall be extended by a period of six months after the date the patent expires (including any patent extensions).
(2) Exception
(c) Market exclusivity for already-marketed drugs
(1) In generalExcept as provided in paragraph (2), if the Secretary determines that information relating to the use of an approved drug in the pediatric population may produce health benefits in that population and makes a written request to the holder of an approved application under section 355(b)(1) of this title for pediatric studies (which shall include a timeframe for completing such studies), the holder agrees to the request, such studies are completed using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and accepted in accordance with subsection (d)(4)—
(A)
(i)(I) the period referred to in subsection (c)(3)(E)(ii) of section 355 of this title, and in subsection (j)(5)(F)(ii) of such section, is deemed to be five years and six months rather than five years, and the references in subsections (c)(3)(E)(ii) and (j)(5)(F)(ii) of such section to four years, to forty-eight months, and to seven and one-half years are deemed to be four and one-half years, fifty-four months, and eight years, respectiv ely; or(II) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(E) of such section, and in clauses (iii) and (iv) of subsection (j)(5)(F) of such section, is deemed to be three years and six months rather than three years; and
(ii) if the drug is designated under section 360bb of this title for a rare disease or condition, the period referred to in section 360cc(a) of this title is deemed to be seven years and six months rather than seven years; and
(B)
(i) if the drug is the subject of—(I) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of section 355 of this title and for which pediatric studies were submitted prior to the expiration of the patent (including any patent extensions); or(II) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 355 of this title,
the period during which an application may not be approved under section 355(c)(3) of this title or section 355(j)(5)(B)(ii) of this title shall be extended by a period of six months after the date the patent expires (including any patent extensions); or
(ii) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the patent infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed, the period during which an application may not be approved under section 355(c)(3) of this title or section 355(j)(5)(B) of this title shall be extended by a period of six months after the date the patent expires (including any patent extensions).
(2) Exception
(d) Conduct of pediatric studies
(1) Request for studies
(A) In general
(B) Single written requestA single written request—
(i) may relate to more than one use of a drug; and
(ii) may include uses that are both approved and unapproved.
(2) Written request for pediatric studies
(A) Request and response
(i) In generalIf the Secretary makes a written request for pediatric studies (including neonates, as appropriate) under subsection (b) or (c), the applicant or holder, not later than 180 days after receiving the written request, shall respond to the Secretary as to the intention of the applicant or holder to act on the request by—(I) indicating when the pediatric studies will be initiated, if the applicant or holder agrees to the request; or(II) indicating that the applicant or holder does not agree to the request and stating the reasons for declining the request.
(ii) Disagree with request
(B) Adverse event reports
(3) Action on submissions
(4) Meeting the studies requirement
(5) Effect of subsection
(6) Consultation
(e) Notice of determinations on studies requirement
(1) In general
(2) Identification of certain drugs
(f) Internal review of written requests and pediatric studies
(1) Internal review
(2) Review of written requests
(3) Review of pediatric studies
(4) Activity by committee
(5) Documentation of committee action
(6) Tracking pediatric studies and labeling changesThe Secretary, in consultation with the committee referred to in paragraph (1), shall track and make available to the public, in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration—
(A) the number of studies conducted under this section and under section 284m of title 42;
(B) the specific drugs and drug uses, including labeled and off-labeled indications, studied under such sections;
(C) the types of studies conducted under such sections, including trial design, the number of pediatric patients studied, and the number of centers and countries involved;
(D) the number of pediatric formulations developed and the number of pediatric formulations not developed and the reasons such formulations were not developed;
(E) the labeling changes made as a result of studies conducted under such sections;
(F) an annual summary of labeling changes made as a result of studies conducted under such sections for distribution pursuant to subsection (k)(2); and
(G) information regarding reports submitted on or after September 27, 2007.
(7) Informing internal review committee
(g) LimitationsNotwithstanding subsection (c)(2), a drug to which the six-month period under subsection (b) or (c) has already been applied—
(1) may receive an additional six-month period under subsection (c)(1)(A)(i)(II) for a supplemental application if all other requirements under this section are satisfied, except that such drug may not receive any additional such period under subsection (c)(1)(B); and
(2) may not receive any additional such period under subsection (c)(1)(A)(ii).
(h) Relationship to pediatric research requirements
(i) Labeling changes
(1) Priority status for pediatric applications and supplementsAny application or supplement to an application under section 355 of this title proposing a labeling change as a result of any pediatric study conducted pursuant to this section—
(A) shall be considered to be a priority application or supplement; and
(B) shall be subject to the performance goals established by the Commissioner for priority drugs.
(2) Dispute resolution
(A) Request for labeling change and failure to agreeIf, on or after September 27, 2007, the Commissioner determines that the sponsor and the Commissioner have been unable to reach agreement on appropriate changes to the labeling for the drug that is the subject of the application, not later than 180 days after the date of submission of the application—
(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and
(ii) if the sponsor of the application does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
(B) Action by the Pediatric Advisory CommitteeNot later than 90 days after receiving a referral under subparagraph (A)(ii), the Pediatric Advisory Committee shall—
(i) review the pediatric study reports; and
(ii) make a recommendation to the Commissioner concerning appropriate labeling changes, if any.
(C) Consideration of recommendations
(D) Misbranding
(E) No effect on authority
(j) Other labeling changes
(k) Dissemination of pediatric information
(1) In general
(2) Dissemination of information regarding labeling changes
(3) Effect of subsection
(l) Adverse event reporting
(1) Reporting in first 18-month period
(2) Reporting in subsequent periods
(3) Preservation of authority
(4) Effect
(m) Clarification of interaction of market exclusivity under this section and market exclusivity awarded to an applicant for approval of a drug under section 355(j) of this titleIf a 180-day period under section 355(j)(5)(B)(iv) of this title overlaps with a 6-month exclusivity period under this section, so that the applicant for approval of a drug under section 355(j) of this title entitled to the 180-day period under that section loses a portion of the 180-day period to which the applicant is entitled for the drug, the 180-day period shall be extended from—
(1) the date on which the 180-day period would have expired by the number of days of the overlap, if the 180-day period would, but for the application of this subsection, expire after the 6-month exclusivity period; or
(2) the date on which the 6-month exclusivity period expires, by the number of days of the overlap if the 180-day period would, but for the application of this subsection, expire during the six-month exclusivity period.
(n) Referral if pediatric studies not submitted
(1) In generalBeginning on September 27, 2007, if pediatric studies of a drug have not been submitted by the date specified in the written request issued or if the applicant or holder does not agree to the request under subsection (d) and if the Secretary, through the committee established under section 355d of this title, determines that there is a continuing need for information relating to the use of the drug in the pediatric population (including neonates, as appropriate), the Secretary shall carry out the following:
(A) For a drug for which a listed patent has not expired, or for which a period of exclusivity eligible for extension under subsection (b)(1) or (c)(1) of this section or under subsection (m)(2) or (m)(3) of section 262 of title 42 has not ended, make a determination regarding whether an assessment shall be required to be submitted under section 355c(b) of this title.
(B) For a drug that has no unexpired listed patents and for which no unexpired periods of exclusivity eligible for extension under subsection (b)(1) or (c)(1) of this section or under subsection (m)(2) or (m)(3) of apply, the Secretary shall refer the drug for inclusion on the list established under
(C) For a drug that is a qualified countermeasure (as defined in section 247d–6a of title 42), a security countermeasure (as defined in section 247d–6b of title 42), or a qualified pandemic or epidemic product (as defined in section 247d–6d of title 42), in addition to any action with respect to such drug under subparagraph (A) or (B), the Secretary shall notify the Assistant Secretary for Preparedness and Response and the Director of the Biomedical Advanced Research and Development Authority of all pediatric studies in the written request issued by the Commissioner of Food and Drugs.
(2) Public notice
(3) Effect of subsection
(o) Prompt approval of drugs when pediatric information is added to labeling
(1) General rule
(2) LabelingNotwithstanding clauses (iii) and (iv) of section 355(j)(5)(F) of this title, clauses (iii) and (iv) of section 355(c)(3)(E) of this title, or section 360cc of this title, the Secretary may require that the labeling of a drug approved pursuant to an application submitted under subsection (b)(2) or (j) of section 355 of this title that omits a pediatric indication or other aspect of labeling as described in paragraph (1) include—
(A) a statement that, because of marketing exclusivity for a manufacturer—
(i) the drug is not labeled for pediatric use; or
(ii) in the case of a drug for which there is an additional pediatric use not referred to in paragraph (1), the drug is not labeled for the pediatric use under paragraph (1); and
(B) a statement of any appropriate pediatric contraindications, warnings, precautions, or other information that the Secretary considers necessary to assure safe use.
(3) Preservation of pediatric exclusivity and extensionsThis subsection does not affect—
(A) the availability or scope of exclusivity under—
(i) this section;
(ii)section 355 of this title for pediatric formulations; or
(iii)section 360cc of this title;
(B) the availability or scope of an extension to any such exclusivity, including an extension under this section or section 355f of this title;
(C) the question of the eligibility for approval under section 355 of this title of any application described in subsection (b)(2) or (j) of such section that omits any other aspect of labeling protected by exclusivity under—
(i) clause (iii) or (iv) of section 355(j)(5)(F) of this title;
(ii) clause (iii) or (iv) of section 355(c)(3)(E) of this title; or
(iii)section 360cc(a) of this title; or
(D) except as expressly provided in paragraphs (1) and (2), the operation of section 355 of this title or section 360cc of this title.
(June 25, 1938, ch. 675, § 505A, as added Pub. L. 105–115, title I, § 111, Nov. 21, 1997, 111 Stat. 2305; amended Pub. L. 107–109, §§ 2, 4, 5(b)(2), 7–11(a), 18(a), 19, Jan. 4, 2002, 115 Stat. 1408, 1411, 1413–1415, 1423, 1424; Pub. L. 108–155, §§ 2(b)(2), 3(a), (b)(1), Dec. 3, 2003, 117 Stat. 1941; Pub. L. 108–173, title XI, § 1104, Dec. 8, 2003, 117 Stat. 2461; Pub. L. 110–85, title V, § 502(a)(1), Sept. 27, 2007, 121 Stat. 876; Pub. L. 111–148, title VII, § 7002(g)(2)(B), Mar. 23, 2010, 124 Stat. 820; Pub. L. 112–144, title V, §§ 501(a), 502(a)(1), (b), 509(a), July 9, 2012, 126 Stat. 1039, 1040, 1047; Pub. L. 113–5, title III, § 307(a), Mar. 13, 2013, 127 Stat. 191; Pub. L. 114–255, div. A, title III, § 3102(2), Dec. 13, 2016, 130 Stat. 1156; Pub. L. 115–52, title V, § 505(a)–(b)(2)(A), title VI, § 608, Aug. 18, 2017, 131 Stat. 1046, 1050; Pub. L. 117–9, § 1(b)(2), Apr. 23, 2021, 135 Stat. 258.)

CITE AS: 21 USC 355a

§ 355b. Adverse-event reporting
(a) Toll-free number in labeling
Not later than one year after January 4, 2002, the Secretary of Health and Human Services shall promulgate a final rule requiring that the labeling of each drug for which an application is approved under section 505 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355] (regardless of the date on which approved) include the toll-free number maintained by the Secretary for the purpose of receiving reports of adverse events regarding drugs and a statement that such number is to be used for reporting purposes only, not to receive medical advice. With respect to the final rule:
(1) The rule shall provide for the implementation of such labeling requirement in a manner that the Secretary considers to be most likely to reach the broadest consumer audience.
(2) In promulgating the rule, the Secretary shall seek to minimize the cost of the rule on the pharmacy profession.
(3) The rule shall take effect not later than 60 days after the date on which the rule is promulgated.
(b) Drugs with pediatric market exclusivity
(1) In general
(2) Rule of construction
(Pub. L. 107–109, § 17, Jan. 4, 2002, 115 Stat. 1422; Pub. L. 108–155, § 3(b)(5), Dec. 3, 2003, 117 Stat. 1942.)

CITE AS: 21 USC 355b

§ 355c. Research into pediatric uses for drugs and biological products
(a) New drugs and biological products
(1) In general
(A) General requirementsExcept with respect to an application for which subparagraph (B) applies, a person that submits, on or after September 27, 2007, an application (or supplement to an application) for a drug—
(i) under section 355 of this title for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; or
(ii) under section 262 of title 42 for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration,
shall submit with the application the assessments described in paragraph (2).
(B) Certain molecularly targeted cancer indicationsA person that submits, on or after the date that is 3 years after August 18, 2017, an original application for a new active ingredient under section 355 of this title or section 262 of title 42, shall submit with the application reports on the investigation described in paragraph (3) if the drug or biological product that is the subject of the application is—
(i) intended for the treatment of an adult cancer; and
(ii) directed at a molecular target that the Secretary determines to be substantially relevant to the growth or progression of a pediatric cancer.
(2) Assessments
(A) In generalThe assessments referred to in paragraph (1)(A) shall contain data, gathered using appropriate formulations for each age group for which the assessment is required, that are adequate—
(i) to assess the safety and effectiveness of the drug or the biological product for the claimed indications in all relevant pediatric subpopulations; and
(ii) to support dosing and administration for each pediatric subpopulation for which the drug or the biological product is safe and effective.
(B) Similar course of disease or similar effect of drug or biological product
(i) In general
(ii) Extrapolation between age groups
(iii) Information on extrapolation
(3) Molecularly targeted pediatric cancer investigation
(A) In general
(B) Extrapolation of data
(C) Deferrals and waivers
(4) Deferral
(A) In generalOn the initiative of the Secretary or at the request of the applicant, the Secretary may defer submission of some or all assessments required under paragraph (1)(A) or reports on the investigation required under paragraph (1)(B) until a specified date after approval of the drug or issuance of the license for a biological product if—
(i) the Secretary finds that—(I) the drug or biological product is ready for approval for use in adults before pediatric studies are complete;(II) pediatric studies should be delayed until additional safety or effectiveness data have been collected; or(III) there is another appropriate reason for deferral; and
(ii) the applicant submits to the Secretary—(I) certification of the grounds for deferring the assessments or reports on the investigation;(II) a pediatric study plan as described in subsection (e);(III) evidence that the studies are being conducted or will be conducted with due diligence and at the earliest possible time; and(IV) a timeline for the completion of such studies.
(B) Deferral extension
(i) In generalOn the initiative of the Secretary or at the request of the applicant, the Secretary may grant an extension of a deferral approved under subparagraph (A) for submission of some or all assessments required under paragraph (1)(A) or reports on the investigation required under paragraph (1)(B) if—(I) the Secretary determines that the conditions described in subclause (II) or (III) of subparagraph (A)(i) continue to be met; and(II) the applicant submits a new timeline under subparagraph (A)(ii)(IV) and any significant updates to the information required under subparagraph (A)(ii).
(ii) Timing and information
(C) Annual review
(i) In generalOn an annual basis following the approval of a deferral under subparagraph (A), the applicant shall submit to the Secretary the following information:(I) Information detailing the progress made in conducting pediatric studies.(II) If no progress has been made in conducting such studies, evidence and documentation that such studies will be conducted with due diligence and at the earliest possible time.(III) Projected completion date for pediatric studies.(IV) The reason or reasons why a deferral or deferral extension continues to be necessary.
(ii) Public availabilityNot later than 90 days after the submission to the Secretary of the information submitted through the annual review under clause (i), the Secretary shall make available to the public in an easily accessible manner, including through the Internet Web site of the Food and Drug Administration—(I) such information;(II) the name of the applicant for the product subject to the assessment or investigation;(III) the date on which the product was approved; and(IV) the date of each deferral or deferral extension under this paragraph for the product.
(5) Waivers
(A) Full waiverOn the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments or reports on the investigation for a drug or biological product under this subsection if the applicant certifies and the Secretary finds that—
(i) necessary studies are impossible or highly impracticable (because, for example, the number of patients is so small or the patients are geographically dispersed);
(ii) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups; or
(iii) the drug or biological product—(I) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients; and(II) is not likely to be used in a substantial number of pediatric patients.
(B) Partial waiverOn the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments or reports on the investigation for a drug or biological product under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that—
(i) necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed);
(ii) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group;
(iii) the drug or biological product—(I) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients in that age group; and(II) is not likely to be used by a substantial number of pediatric patients in that age group; or
(iv) the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed.
(C) Pediatric formulation not possible
(D) Labeling requirement
(b) Marketed drugs and biological products
(1) In generalThe Secretary may (by order in the form of a letter) require the sponsor or holder of an approved application for a drug under section 355 of this title or the holder of a license for a biological product under section 262 of title 42 to submit by a specified date the assessments described in subsection (a)(2), if the Secretary finds that—
(A)
(i) the drug or biological product is used for a substantial number of pediatric patients for the labeled indications; and
(ii) adequate pediatric labeling could confer a benefit on pediatric patients;
(B) there is reason to believe that the drug or biological product would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for 1 or more of the claimed indications; or
(C) the absence of adequate pediatric labeling could pose a risk to pediatric patients.
(2) Waivers
(A) Full waiverAt the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments under this subsection if the applicant certifies and the Secretary finds that—
(i) necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed); or
(ii) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups.
(B) Partial waiverAt the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that—
(i) necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed);
(ii) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group;
(iii)(I) the drug or biological product—(aa) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients in that age group; and(bb) is not likely to be used in a substantial number of pediatric patients in that age group; and(II) the absence of adequate labeling could not pose significant risks to pediatric patients; or
(iv) the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed.
(C) Pediatric formulation not possible
(D) Labeling requirement
(3) Effect of subsection
(c) Meaningful therapeutic benefitFor the purposes of paragraph (4)(A)(iii)(I) and (4)(B)(iii)(I) of subsection (a) and paragraphs (1)(B) and (2)(B)(iii)(I)(aa) of subsection (b), a drug or biological product shall be considered to represent a meaningful therapeutic benefit over existing therapies if the Secretary determines that—
(1) if approved, the drug or biological product could represent an improvement in the treatment, diagnosis, or prevention of a disease, compared with marketed products adequately labeled for that use in the relevant pediatric population; or
(2) the drug or biological product is in a class of products or for an indication for which there is a need for additional options.
(d) Submission of assessments and reports on the investigationIf a person fails to submit a required assessment described in subsection (a)(2) or the investigation described in subsection (a)(3), fails to meet the applicable requirements in subsection (a)(4), or fails to submit a request for approval of a pediatric formulation described in subsection (a) or (b), in accordance with applicable provisions of subsections (a) and (b), the following shall apply:
(1) Beginning 270 days after July 9, 2012, the Secretary shall issue a non-compliance letter to such person informing them of such failure to submit or meet the requirements of the applicable subsection. Such letter shall require the person to respond in writing within 45 calendar days of issuance of such letter. Such response may include the person’s request for a deferral extension if applicable. Such letter and the person’s written response to such letter shall be made publicly available on the Internet Web site of the Food and Drug Administration 60 calendar days after issuance, with redactions for any trade secrets and confidential commercial information. If the Secretary determines that the letter was issued in error, the requirements of this paragraph shall not apply. The Secretary shall inform the Pediatric Advisory Committee of letters issued under this paragraph and responses to such letters.
(2) The drug or biological product that is the subject of an assessment described in subsection (a)(2) or the investigation described in subsection (a)(3), applicable requirements in subsection (a)(4), or request for approval of a pediatric formulation, may be considered misbranded solely because of that failure and subject to relevant enforcement action (except that the drug or biological product shall not be subject to action under section 333 of this title), but such failure shall not be the basis for a proceeding—
(A) to withdraw approval for a drug under section 355(e) of this title; or
(B) to revoke the license for a biological product under section 262 of title 42.
(e) Pediatric study plans
(1) In general
(2) Timing; span; meetings
(A) TimingAn applicant shall submit the initial pediatric study plan under paragraph (1)—
(i) before the date on which the applicant submits the assessments under subsection (a)(2) or the investigation described in subsection (a)(3); and
(ii) not later than—(I) 60 calendar days after the date of the end-of-Phase 2 meeting (as such term is used in section 312.47 of title 21, Code of Federal Regulations, or successor regulations); or(II) such other time as may be agreed upon between the Secretary and the applicant.
Nothing in this section shall preclude the Secretary from accepting the submission of an initial pediatric study plan earlier than the date otherwise applicable under this subparagraph.
(B) Content of initial pediatric study planThe initial pediatric study plan shall include—
(i) an outline of the pediatric study or studies that the applicant plans to conduct (including, to the extent practicable study objectives and design, age groups, relevant endpoints, and statistical approach);
(ii) any request for a deferral, partial waiver, or waiver under this section, if applicable, along with any supporting information; and
(iii) other information specified in the regulations promulgated under paragraph (7).
(C) MeetingsThe Secretary—
(i) shall meet with the applicant—(I) if requested by the applicant with respect to a drug or biological product that is intended to treat a serious or life-threatening disease or condition, to discuss preparation of the initial pediatric study plan, not later than the end-of-Phase 1 meeting (as such term is used in section 312.82(b) of title 21, Code of Federal Regulations, or successor regulations) or within 30 calendar days of receipt of such request, whichever is later;(II) to discuss the initial pediatric study plan as soon as practicable, but not later than 90 calendar days after the receipt of such plan under subparagraph (A); and(III) to discuss the bases for the deferral under subsection (a)(4) or a full or partial waiver under subsection (a)(5);
(ii) may determine that a written response to the initial pediatric study plan is sufficient to communicate comments on the initial pediatric study plan, and that no meeting under clause (i)(II) is necessary; and
(iii) if the Secretary determines that no meeting under clause (i)(II) is necessary, shall so notify the applicant and provide written comments of the Secretary as soon as practicable, but not later than 90 calendar days after the receipt of the initial pediatric study plan.
(3) Agreed initial pediatric study plan
(4) Deferral and waiver
(5) Amendments to the agreed initial pediatric study plan
(6) Internal committee
(7) Required rulemaking
(f) Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers
(1) Review
(2) Activity by committee
(3) Documentation of committee action
(4) Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers
(5) Retrospective review of pediatric assessments, deferrals, and waivers
(6) Tracking of assessments and labeling changesThe Secretary, in consultation with the committee referred to in paragraph (1), shall track and make available to the public in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration—
(A) the number of assessments conducted under this section;
(B) the specific drugs and biological products and their uses assessed under this section;
(C) the types of assessments conducted under this section, including trial design, the number of pediatric patients studied, and the number of centers and countries involved;
(D) aggregated on an annual basis—
(i) the total number of deferrals and deferral extensions requested and granted under this section and, if granted, the reasons for each such deferral or deferral extension;
(ii) the timeline for completion of the assessments;
(iii) the number of assessments completed and pending; and
(iv) the number of postmarket non-compliance letters issued pursuant to subsection (d), and the recipients of such letters;
(E) the number of waivers requested and granted under this section and, if granted, the reasons for the waivers;
(F) the number of pediatric formulations developed and the number of pediatric formulations not developed and the reasons any such formulation was not developed;
(G) the labeling changes made as a result of assessments conducted under this section;
(H) an annual summary of labeling changes made as a result of assessments conducted under this section for distribution pursuant to subsection (h)(2);
(I) an annual summary of information submitted pursuant to subsection (a)(4)(C); and
(J) the number of times the committee referred to in paragraph (1) made a recommendation to the Secretary under paragraph (4) regarding priority review, the number of times the Secretary followed or did not follow such a recommendation, and, if not followed, the reasons why such a recommendation was not followed.
(g) Labeling changes
(1) Dispute resolution
(A) Request for labeling change and failure to agreeIf, on or after September 27, 2007, the Commissioner determines that a sponsor and the Commissioner have been unable to reach agreement on appropriate changes to the labeling for the drug that is the subject of the application or supplement, not later than 180 days after the date of the submission of the application or supplement that receives a priority review or 330 days after the date of the submission of an application or supplement that receives a standard review—
(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and
(ii) if the sponsor does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
(B) Action by the Pediatric Advisory CommitteeNot later than 90 days after receiving a referral under subparagraph (A)(ii), the Pediatric Advisory Committee shall—
(i) review the pediatric study reports; and
(ii) make a recommendation to the Commissioner concerning appropriate labeling changes, if any.
(C) Consideration of recommendations
(D) Misbranding
(E) No effect on authority
(2) Other labeling changes
(h) Dissemination of pediatric information
(1) In general
(2) Dissemination of information regarding labeling changes
(3) Effect of subsection
(i) Adverse event reporting
(1) Reporting in first 18-month period
(2) Reporting in subsequent periods
(3) Preservation of authority
(4) Effect
(j) Scope of authority
(k) Relation to orphan drugs
(1) In general; exemption for orphan indications
(2) Applicability despite orphan designation of certain indications
(l) New active ingredient
(1) Non-interchangeable biosimilar biological product
(2) Interchangeable biosimilar biological product
(m) List of primary molecular targets
(1) In generalWithin one year of August 18, 2017, the Secretary shall establish and update regularly, and shall publish on the internet website of the Food and Drug Administration—
(A) a list of molecular targets considered, on the basis of data the Secretary determines to be adequate, to be substantially relevant to the growth and progression of a pediatric cancer, and that may trigger the requirements under this section; and
(B) a list of molecular targets of new cancer drugs and biological products in development for which pediatric cancer study requirements under this section will be automatically waived.
(2) Consultation
(3) Rule of constructionNothing in paragraph (1) shall be construed—
(A) to require the inclusion of a molecular target on the list published under such paragraph as a condition for triggering the requirements under subsection (a)(1)(B) with respect to a drug or biological product directed at such molecular target; or
(B) to authorize the disclosure of confidential commercial information, as prohibited under section 331(j) of this title or section 1905 of title 18.
(June 25, 1938, ch. 675, § 505B, as added Pub. L. 108–155, § 2(a), Dec. 3, 2003, 117 Stat. 1936; amended Pub. L. 110–85, title IV, § 402(a), Sept. 27, 2007, 121 Stat. 866; Pub. L. 111–148, title VII, § 7002(d)(2), Mar. 23, 2010, 124 Stat. 816

CITE AS: 21 USC 355c

§ 355c–1. Report
(a) In general
(b) ContentsEach report under subsection (a) shall include—
(1) an assessment of the effectiveness of sections 355a and 355c of this title in improving information about pediatric uses for approved drugs and biological products, including the number and type of labeling changes made since July 9, 2012, and the importance of such uses in the improvement of the health of children;
(2) the number of required studies under such section 355c of this title that have not met the initial deadline provided under such section 355c of this title, including—
(A) the number of deferrals and deferral extensions granted and the reasons such extensions were granted;
(B) the number of waivers and partial waivers granted; and
(C) the number of letters issued under subsection (d) of such section 355c of this title;
(3) an assessment of the timeliness and effectiveness of pediatric study planning since July 9, 2012, including the number of initial pediatric study plans not submitted in accordance with the requirements of subsection (e) of such section 355c of this title and any resulting rulemaking;
(4) the number of written requests issued, accepted, and declined under such section 355a of this title since July 9, 2012, and a listing of any important gaps in pediatric information as a result of such declined requests;
(5) a description and current status of referrals made under subsection (n) of such section 355a of this title;
(6) an assessment of the effectiveness of studying biological products in pediatric populations under such sections 355a and 355c of this title and section 284m of title 42;
(7)
(A) the efforts made by the Secretary to increase the number of studies conducted in the neonatal population (including efforts made to encourage the conduct of appropriate studies in neonates by companies with products that have sufficient safety and other information to make the conduct of the studies ethical and safe); and
(B) the results of such efforts;
(8)
(A) the number and importance of drugs and biological products for children with cancer that are being tested as a result of the programs under such sections 355a and 355c of this title and under section 284m of title 42; and
(B) any recommendations for modifications to such programs that would lead to new and better therapies for children with cancer, including a detailed rationale for each recommendation;
(9) any recommendations for modification to such programs that would improve pediatric drug research and increase pediatric labeling of drugs and biological products;
(10) an assessment of the successes of and limitations to studying drugs for rare diseases under such sections 355a and 355c of this title;
(11) an assessment of the impact of the amendments to such section 355c of this title made by the FDA Reauthorization Act of 2017 on pediatric research and labeling of drugs and biological products and pediatric labeling of molecularly targeted drugs and biological products for the treatment of cancer;
(12) an assessment of the efforts of the Secretary to implement the plan developed under section 505C–1 of the Federal Food, Drug, and Cosmetic Act,1
1 See References in Text note below.
regarding earlier submission of pediatric studies under sections 355a and 355c of this title and section 262(m) of title 42, including—
(A) the average length of time after the approval of an application under section 355(b)(1) of this title or section 262(a) of title 42 before studies conducted pursuant to such section 355a of this title, 355c of this title, or section 262(m) of title 42 are completed, submitted, and incorporated into labeling;
(B) the average length of time after the receipt of a proposed pediatric study request before the Secretary responds to such request;
(C) the average length of time after the submission of a proposed pediatric study request before the Secretary issues a written request for such studies;
(D) the number of written requests issued for each investigational new drug or biological product prior to the submission of an application under section 355(b)(1) of this title or section 262(a) of title 42; and
(E) the average number, and range of numbers, of amendments to written requests issued, and the time the Secretary requires to review and act on proposed amendments to written requests;
(13) a list of sponsors of applications or holders of approved applications who received exclusivity under such section 355a of this title or such section 262(m) of title 42 after receiving a letter issued under such section 355c(d)(1) of this title for any drug or biological product before the studies referred to in such letter were completed and submitted;
(14) a list of assessments and investigations required under such section 355c of this title;
(15) how many requests under such section 355a of this title for molecular targeted cancer drugs, as defined by subsection (a)(1)(B) of such section 355c of this title, approved prior to 3 years after August 18, 2017, have been issued by the Food and Drug Administration, and how many such requests have been completed; and
(16) the Secretary’s assessment of the overall impact of the amendments made by section 504 of the FDA Reauthorization Act of 2017 on the conduct and effectiveness of pediatric cancer research and the orphan drug program, as well any subsequent recommendations.
(c) Stakeholder comment
(Pub. L. 112–144, title V, § 508, July 9, 2012, 126 Stat. 1045; Pub. L. 115–52, title V, § 504(d), Aug. 18, 2017, 131 Stat. 1044.)

CITE AS: 21 USC 355c-1

§ 355d. Internal committee for review of pediatric plans, assessments, deferrals, deferral extensions, and waivers

The Secretary shall establish an internal committee within the Food and Drug Administration to carry out the activities as described in sections 355a(f) and 355c(f) of this title. Such internal committee shall include employees of the Food and Drug Administration, with expertise in pediatrics (including representation from the Office of Pediatric Therapeutics), biopharmacology, statistics, chemistry, legal issues, pediatric ethics, neonatology, and the appropriate expertise pertaining to the pediatric product under review, such as expertise in child and adolescent psychiatry or pediatric rare diseases, and other individuals designated by the Secretary.

(June 25, 1938, ch. 675, § 505C, as added Pub. L. 110–85, title IV, § 403, Sept. 27, 2007, 121 Stat. 875; amended Pub. L. 112–144, title V, § 509(c), July 9, 2012, 126 Stat. 1049; Pub. L. 115–52, title V, § 505(f), Aug. 18, 2017, 131 Stat. 1047.)

CITE AS: 21 USC 355d

§ 355e. Pharmaceutical security
(a) In general
(b) Standards development
(1) In general
(2) Standardized numeral identifier
(3) Promising technologies
The standards developed under this subsection shall address promising technologies, which may include—
(A) radio frequency identification technology;
(B) nanotechnology;
(C) encryption technologies; and
(D) other track-and-trace or authentication technologies.
(4) Interagency collaboration
In carrying out this subsection, the Secretary shall consult with Federal health and security agencies, including—
(A) the Department of Justice;
(B) the Department of Homeland Security;
(C) the Department of Commerce; and
(D) other appropriate Federal and State agencies.
(c) Inspection and enforcement
(1) In general
(2) Activities
(d) Definition
(June 25, 1938, ch. 675, § 505D, as added Pub. L. 110–85, title IX, § 913, Sept. 27, 2007, 121 Stat. 952.)

CITE AS: 21 USC 355e

§ 355f. Extension of exclusivity period for new qualified infectious disease products
(a) Extension
(b) Relation to pediatric exclusivity
(c) LimitationsSubsection (a) does not apply to the approval of—
(1) a supplement to an application under section 355(b) of this title for any qualified infectious disease product for which an extension described in subsection (a) is in effect or has expired;
(2) a subsequent application filed with respect to a product approved under section 355 of this title for a change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength;
(3) a product that does not meet the definition of a qualified infectious disease product under subsection (g) based upon its approved uses; or
(4) an application pursuant to section 262(a) of title 42.
(d) Designation
(1) In general
(2) Limitation
(3) Revocation of designation
(e) Regulations
(1) In general
(2) ProcedureIn promulgating a regulation implementing this section, the Secretary shall—
(A) issue a notice of proposed rulemaking that includes the proposed regulation;
(B) provide a period of not less than 60 days for comments on the proposed regulation; and
(C) publish the final regulation not less than 30 days before the effective date of the regulation.
(3) Restrictions
(4) Designation prior to regulations
(f) Qualifying pathogen
(1) DefinitionIn this section, the term “qualifying pathogen” means a pathogen identified and listed by the Secretary under paragraph (2) that has the potential to pose a serious threat to public health, such as—
(A) resistant gram positive pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus;
(B) multi-drug resistant gram negative bacteria, including Acinetobacter, Klebsiella, Pseudomonas, and E. coli species;
(C) multi-drug resistant tuberculosis; and
(D) Clostridium difficile.
(2) List of qualifying pathogens
(A) In general
(B) ConsiderationsIn establishing and maintaining the list of pathogens described under this section, the Secretary shall—
(i) consider—(I) the impact on the public health due to drug-resistant organisms in humans;(II) the rate of growth of drug-resistant organisms in humans;(III) the increase in resistance rates in humans; and(IV) the morbidity and mortality in humans; and
(ii) consult with experts in infectious diseases and antibiotic resistance, including the Centers for Disease Control and Prevention, the Food and Drug Administration, medical professionals, and the clinical research community.
(C) Review
(g) Qualified infectious disease productThe term “qualified infectious disease product” means a drug (including a biological product), including an antibacterial or antifungal drug, for human use that—
(1) acts on bacteria or fungi or on substances produced by such bacteria or fungi; and
(2) is intended to treat a serious or life-threatening infection, including such an infection caused by—
(A) an antibacterial or antifungal resistant pathogen, including novel or emerging infectious pathogens; or
(B) qualifying pathogens listed by the Secretary under subsection (f).
(June 25, 1938, ch. 675, § 505E, as added Pub. L. 112–144, title VIII, § 801(a), July 9, 2012, 126 Stat. 1077; amended Pub. L. 117–328, div. FF, title III, § 3212(a), Dec. 29, 2022, 136 Stat. 5826.)

CITE AS: 21 USC 355f

§ 355g. Utilizing real world evidence
(a) In generalThe Secretary shall establish a program to evaluate the potential use of real world evidence—
(1) to help to support the approval of a new indication for a drug approved under section 355(c) of this title; and
(2) to help to support or satisfy postapproval study requirements.
(b) Real world evidence defined
(c) Program framework
(1) In general
(2) Contents of frameworkThe framework shall include information describing—
(A) the sources of real world evidence, including ongoing safety surveillance, observational studies, registries, claims, and patient-centered outcomes research activities;
(B) the gaps in data collection activities;
(C) the standards and methodologies for collection and analysis of real world evidence; and
(D) the priority areas, remaining challenges, and potential pilot opportunities that the program established under this section will address.
(3) Consultation
(A) In general
(B) ProcessThe consultation under subparagraph (A) may be carried out through approaches such as—
(i) a public-private partnership with the entities described in such subparagraph in which the Secretary may participate;
(ii) a contract, grant, or other arrangement, as the Secretary determines appropriate, with such a partnership or an independent research organization; or
(iii) public workshops with the entities described in such subparagraph.
(d) Program implementation
(e) Guidance for industryThe Secretary shall—
(1) utilize the program established under subsection (a), its activities, and any subsequent pilots or written reports, to inform a guidance for industry on—
(A) the circumstances under which sponsors of drugs and the Secretary may rely on real world evidence for the purposes described in paragraphs (1) and (2) of subsection (a); and
(B) the appropriate standards and methodologies for collection and analysis of real world evidence submitted for such purposes;
(2) not later than 5 years after December 13, 2016, issue draft guidance for industry as described in paragraph (1); and
(3) not later than 18 months after the close of the public comment period for the draft guidance described in paragraph (2), issue revised draft guidance or final guidance.
(f) Rule of construction
(1) In general
(2) Standards of evidence and Secretary’s authorityThis section shall not be construed to alter—
(A) the standards of evidence under—
(i) subsection (c) or (d) of section 355 of this title, including the substantial evidence standard in such subsection (d); or
(ii)section 262(a) of title 42; or
(B) the Secretary’s authority to require postapproval studies or clinical trials, or the standards of evidence under which studies or trials are evaluated.
(June 25, 1938, ch. 675, § 505F, as added Pub. L. 114–255, div. A, title III, § 3022, Dec. 13, 2016, 130 Stat. 1096; amended Pub. L. 115–52, title IX, § 901(c), (d), Aug. 18, 2017, 131 Stat. 1076.)

CITE AS: 21 USC 355g

§ 355h. Regulation of certain nonprescription drugs that are marketed without an approved drug application
(a) Nonprescription drugs marketed without an approved applicationNonprescription drugs marketed without an approved drug application under section 355 of this title, as of March 27, 2020, shall be treated in accordance with this subsection.
(1) Drugs subject to a final monograph; category I drugs subject to a tentative final monographA drug is deemed to be generally recognized as safe and effective under section 321(p)(1) of this title, not a new drug under section 321(p) of this title, and not subject to section 353(b)(1) of this title, if—
(A) the drug is—
(i) in conformity with the requirements for nonprescription use of a final monograph issued under part 330 of title 21, Code of Federal Regulations (except as provided in paragraph (2)), the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and
(ii) except as permitted by an order issued under subsection (b) or, in the case of a minor change in the drug, in conformity with an order issued under subsection (c), in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title; or
(B) the drug is—
(i) classified in category I for safety and effectiveness under a tentative final monograph that is the most recently applicable proposal or determination issued under part 330 of title 21, Code of Federal Regulations;
(ii) in conformity with the proposed requirements for nonprescription use of such tentative final monograph, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and
(iii) except as permitted by an order issued under subsection (b) or, in the case of a minor change in the drug, in conformity with an order issued under subsection (c), in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title.
(2) Treatment of sunscreen drugs
(3) Category III drugs subject to a tentative final monograph; category I drugs subject to proposed monograph or advance notice of proposed rulemakingA drug that is not described in paragraph (1), (2), or (4) is not required to be the subject of an application approved under section 355 of this title, and is not subject to section 353(b)(1) of this title, if—
(A) the drug is—
(i) classified in category III for safety or effectiveness in the preamble of a proposed rule establishing a tentative final monograph that is the most recently applicable proposal or determination for such drug issued under part 330 of title 21, Code of Federal Regulations;
(ii) in conformity with—(I) the conditions of use, including indication and dosage strength, if any, described for such category III drug in such preamble or in an applicable subsequent proposed rule;(II) the proposed requirements for drugs classified in such tentative final monograph in category I in the most recently proposed rule establishing requirements related to such tentative final monograph and in any final rule establishing requirements that are applicable to the drug; and(III) the general requirements for nonprescription drugs and conditions or requirements under subsection (b) or (k); and
(iii) in a dosage form that, immediately prior to March 27, 2020, had been used to a material extent and for a material time under section 321(p)(2) of this title; or
(B) the drug is—
(i) classified in category I for safety and effectiveness under a proposed monograph or advance notice of proposed rulemaking that is the most recently applicable proposal or determination for such drug issued under part 330 of title 21, Code of Federal Regulations;
(ii) in conformity with the requirements for nonprescription use of such proposed monograph or advance notice of proposed rulemaking, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsection (b) or (k); and
(iii) in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title.
(4) Category II drugs deemed new drugs
(5) Drugs not GRASE deemed new drugs
(6) Other drugs deemed new drugsExcept as provided in subsection (m), a drug is deemed to be a new drug under section 321(p) of this title and misbranded under section 352(ee) of this title if the drug—
(A) is not subject to section 353(b)(1) of this title; and
(B) is not described in paragraph (1), (2), (3), (4), or (5), or subsection (b)(1)(B).
(b) Administrative orders
(1) In general
(A) DeterminationThe Secretary may, on the initiative of the Secretary or at the request of one or more requestors, issue an administrative order determining whether there are conditions under which a specific drug, a class of drugs, or a combination of drugs, is determined to be—
(i) not subject to section 353(b)(1) of this title; and
(ii) generally recognized as safe and effective under section 321(p)(1) of this title.
(B) EffectA drug or combination of drugs shall be deemed to not require approval under section 355 of this title if such drug or combination of drugs—
(i) is determined by the Secretary to meet the conditions specified in clauses (i) and (ii) of subparagraph (A);
(ii) is marketed in conformity with an administrative order under this subsection;
(iii) meets the general requirements for nonprescription drugs; and
(iv) meets the requirements under subsections (c) and (k).
(C) StandardThe Secretary shall find that a drug is not generally recognized as safe and effective under section 321(p)(1) of this title if—
(i) the evidence shows that the drug is not generally recognized as safe and effective under section 321(p)(1) of this title; or
(ii) the evidence is inadequate to show that the drug is generally recognized as safe and effective under section 321(p)(1) of this title.
(2) Administrative orders initiated by the Secretary
(A) In generalIn issuing an administrative order under paragraph (1) upon the Secretary’s initiative, the Secretary shall—
(i) make reasonable efforts to notify informally, not later than 2 business days before the issuance of the proposed order, the sponsors of drugs who have a listing in effect under section 360(j) of this title for the drugs or combination of drugs that will be subject to the administrative order;
(ii) after any such reasonable efforts of notification—(I) issue a proposed administrative order by publishing it on the website of the Food and Drug Administration and include in such order the reasons for the issuance of such order; and(II) publish a notice of availability of such proposed order in the Federal Register;
(iii) except as provided in subparagraph (B), provide for a public comment period with respect to such proposed order of not less than 45 calendar days; and
(iv) if, after completion of the proceedings specified in clauses (i) through (iii), the Secretary determines that it is appropriate to issue a final administrative order—(I) issue the final administrative order, together with a detailed statement of reasons, which order shall not take effect until the time for requesting judicial review under paragraph (3)(D)(ii) has expired;(II) publish a notice of such final administrative order in the Federal Register;(III) afford requestors of drugs that will be subject to such order the opportunity for formal dispute resolution up to the level of the Director of the Center for Drug Evaluation and Research, which initially must be requested within 45 calendar days of the issuance of the order, and, for subsequent levels of appeal, within 30 calendar days of the prior decision; and(IV) except with respect to drugs described in paragraph (3)(B), upon completion of the formal dispute resolution procedure, inform the persons which sought such dispute resolution of their right to request a hearing.
(B) ExceptionsWhen issuing an administrative order under paragraph (1) on the Secretary’s initiative proposing to determine that a drug described in subsection (a)(3) is not generally recognized as safe and effective under section 321(p)(1) of this title, the Secretary shall follow the procedures in subparagraph (A), except that—
(i) the proposed order shall include notice of—(I) the general categories of data the Secretary has determined necessary to establish that the drug is generally recognized as safe and effective under section 321(p)(1) of this title; and(II) the format for submissions by interested persons;
(ii) the Secretary shall provide for a public comment period of no less than 180 calendar days with respect to such proposed order, except when the Secretary determines, for good cause, that a shorter period is in the interest of public health; and
(iii) any person who submits data in such comment period shall include a certification that the person has submitted all evidence created, obtained, or received by that person that is both within the categories of data identified in the proposed order and relevant to a determination as to whether the drug is generally recognized as safe and effective under section 321(p)(1) of this title.
(3) Hearings; judicial review
(A) In general
(B) No hearing required with respect to orders relating to certain drugs
(i) In generalThe Secretary shall not be required to provide notice and an opportunity for a hearing pursuant to paragraph (2)(A)(iv) if the final administrative order involved relates to a drug—(I) that is described in subsection (a)(3)(A); and(II) with respect to which no human or non-human data studies relevant to the safety or effectiveness of such drug have been submitted to the administrative record since the issuance of the most recent tentative final monograph relating to such drug.
(ii) Human data studies and non-human data definedIn this subparagraph:(I) The term “human data studies” means clinical trials of safety or effectiveness (including actual use studies), pharmacokinetics studies, or bioavailability studies.(II) The term “non-human data” means data from testing other than with human subjects which provides information concerning safety or effectiveness.
(C) Hearing procedures
(i) Denial of request for hearing
(ii) Single hearing for multiple related requests
(iii) Presiding officerThe presiding officer of a hearing requested under subparagraph (A) shall—(I) be designated by the Secretary;(II) not be an employee of the Center for Drug Evaluation and Research; and(III) not have been previously involved in the development of the administrative order involved or proceedings relating to that administrative order.
(iv) Rights of parties to hearing
(v) Final decision(I) At the conclusion of a hearing requested under subparagraph (A), the presiding officer of the hearing shall issue a decision containing findings of fact and conclusions of law. The decision of the presiding officer shall be final.(II) The final decision may not take effect until the period under subparagraph (D)(ii) for submitting a request for judicial review of such decision expires.
(D) Judicial review of final administrative order
(i) In general
(ii) Period to submit a request for judicial reviewA person eligible to request a hearing under this paragraph and seeking judicial review of a final administrative order issued under this subsection shall file such request for judicial review not later than 60 calendar days after the latest of—(I) the date on which notice of such order is published;(II) the date on which a hearing with respect to such order is denied under subparagraph (B) or (C)(i);(III) the date on which a final decision is made following a hearing under subparagraph (C)(v); or(IV) if no hearing is requested, the date on which the time for requesting a hearing expires.
(4) Expedited procedure with respect to administrative orders initiated by the Secretary
(A) Imminent hazard to the public health
(i) In generalIn the case of a determination by the Secretary that a drug, class of drugs, or combination of drugs subject to this section poses an imminent hazard to the public health, the Secretary, after first making reasonable efforts to notify, not later than 48 hours before issuance of such order under this subparagraph, sponsors who have a listing in effect under section 360(j) of this title for such drug or combination of drugs—(I) may issue an interim final administrative order for such drug, class of drugs, or combination of drugs under paragraph (1), together with a detailed statement of the reasons for such order;(II) shall publish in the Federal Register a notice of availability of any such order; and(III) shall provide for a public comment period of at least 45 calendar days with respect to such interim final order.
(ii) Nondelegation
(B) Safety labeling changes
(i) In generalIn the case of a determination by the Secretary that a change in the labeling of a drug, class of drugs, or combination of drugs subject to this section is reasonably expected to mitigate a significant or unreasonable risk of a serious adverse event associated with use of the drug, the Secretary may—(I) make reasonable efforts to notify informally, not later than 48 hours before the issuance of the interim final order, the sponsors of drugs who have a listing in effect under section 360(j) of this title for such drug or combination of drugs;(II) after reasonable efforts of notification, issue an interim final administrative order in accordance with paragraph (1) to require such change, together with a detailed statement of the reasons for such order;(III) publish in the Federal Register a notice of availability of such order; and(IV) provide for a public comment period of at least 45 calendar days with respect to such interim final order.
(ii) Content of order
(C) Effective date
(D) Final orderAfter the completion of the proceedings in subparagraph (A) or (B), the Secretary shall—
(i) issue a final order in accordance with paragraph (1);
(ii) publish a notice of availability of such final administrative order in the Federal Register; and
(iii) afford sponsors of such drugs that will be subject to such an order the opportunity for formal dispute resolution up to the level of the Director of the Center for Drug Evaluation and Research, which must initially be within 45 calendar days of the issuance of the order, and for subsequent levels of appeal, within 30 calendar days of the prior decision.
(E) Hearings
(F) Timing
(i) Final order and hearingThe Secretary shall—(I) not later than 6 months after the date on which the comment period closes under subparagraph (A) or (B), issue a final order in accordance with paragraph (1); and(II) not later than 12 months after the date on which such final order is issued, complete any hearing under subparagraph (E).
(ii) Dispute resolution request
(G) Judicial review
(5) Administrative order initiated at the request of a requestor
(A) In generalIn issuing an administrative order under paragraph (1) at the request of a requestor with respect to certain drugs, classes of drugs, or combinations of drugs—
(i) the Secretary shall, after receiving a request under this subparagraph, determine whether the request is sufficiently complete and formatted to permit a substantive review;
(ii) if the Secretary determines that the request is sufficiently complete and formatted to permit a substantive review, the Secretary shall—(I) file the request; and(II) initiate proceedings with respect to issuing an administrative order in accordance with paragraphs (2) and (3); and
(iii) except as provided in paragraph (6), if the Secretary determines that a request does not meet the requirements for filing or is not sufficiently complete and formatted to permit a substantive review, the requestor may demand that the request be filed over protest, and the Secretary shall initiate proceedings to review the request in accordance with paragraph (2)(A).
(B) Request to initiate proceedings
(i) In generalA requestor seeking an administrative order under paragraph (1) with respect to certain drugs, classes of drugs, or combinations of drugs, shall submit to the Secretary a request to initiate proceedings for such order in the form and manner as specified by the Secretary. Such requestor may submit a request under this subparagraph for the issuance of an administrative order—(I) determining whether a drug is generally recognized as safe and effective under section 321(p)(1) of this title, exempt from section 353(b)(1) of this title, and not required to be the subject of an approved application under section 355 of this title; or(II) determining whether a change to a condition of use of a drug is generally recognized as safe and effective under section 321(p)(1) of this title, exempt from section 353(b)(1) of this title, and not required to be the subject of an approved application under section 355 of this title, if, absent such a changed condition of use, such drug is—(aa) generally recognized as safe and effective under section 321(p)(1) of this title in accordance with subsection (a)(1), (a)(2), or an order under this subsection; or(bb) subject to subsection (a)(3), but only if such requestor initiates such request in conjunction with a request for the Secretary to determine whether such drug is generally recognized as safe and effective under section 321(p)(1) of this title, which is filed by the Secretary under subparagraph (A)(ii).
(ii) Exception
(iii) Withdrawal
(C) Exclusivity
(i) In generalA final administrative order issued in response to a request under this section shall have the effect of authorizing solely the order requestor (or the licensees, assignees, or successors in interest of such requestor with respect to the subject of such order), for a period of 18 months following the effective date of such final order and beginning on the date the requestor may lawfully market such drugs pursuant to the order, to market drugs—(I) incorporating changes described in clause (ii); and(II) subject to the limitations under clause (iv).
(ii) Changes describedA change described in this clause is a change subject to an order specified in clause (i), which—(I) provides for a drug to contain an active ingredient (including any ester or salt of the active ingredient) not previously incorporated in a drug described in clause (iii); or(II) provides for a change in the conditions of use of a drug, for which new human data studies conducted or sponsored by the requestor (or for which the requestor has an exclusive right of reference) were essential to the issuance of such order.
(iii) Drugs describedThe drugs described in this clause are drugs—(I) specified in subsection (a)(1), (a)(2), or (a)(3);(II) subject to a final order issued under this section;(III) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title); or(IV) described in subsection (m)(1), other than drugs subject to an active enforcement action under subchapter III of this chapter.
(iv) Limitations on exclusivity(I) In generalOnly one 18-month period under this subparagraph shall be granted, under each order described in clause (i), with respect to changes (to the drug subject to such order) which are either—(aa) changes described in clause (ii)(I), relating to active ingredients; or(bb) changes described in clause (ii)(II), relating to conditions of use.(II) No exclusivity allowedNo exclusivity shall apply to changes to a drug which are—(aa) the subject of a Tier 2 OTC monograph order request (as defined in section 379j–71 of this title);(bb) safety-related changes, as defined by the Secretary, or any other changes the Secretary considers necessary to assure safe use; or(cc) changes related to methods of testing safety or efficacy.
(v) New human data studies definedIn this subparagraph, the term “new human data studies” means clinical trials of safety or effectiveness (including actual use studies), pharmacokinetics studies, or bioavailability studies, the results of which—(I) have not been relied on by the Secretary to support—(aa) a proposed or final determination that a drug described in subclause (I), (II), or (III) of clause (iii) is generally recognized as safe and effective under section 321(p)(1) of this title; or(bb) approval of a drug that was approved under section 355 of this title; and(II) do not duplicate the results of another study that was relied on by the Secretary to support—(aa) a proposed or final determination that a drug described in subclause (I), (II), or (III) of clause (iii) is generally recognized as safe and effective under section 321(p)(1) of this title; or(bb) approval of a drug that was approved under section 355 of this title.
(vi) Notification of drug not available for saleA requestor that is granted exclusivity with respect to a drug under this subparagraph shall notify the Secretary in writing within 1 year of the issuance of the final administrative order if the drug that is the subject of such order will not be available for sale within 1 year of the date of issuance of such order. The requestor shall include with such notice the—(I) identity of the drug by established name and by proprietary name, if any;(II) strength of the drug;(III) date on which the drug will be available for sale, if known; and(IV) reason for not marketing the drug after issuance of the order.
(6) Information regarding safe nonprescription marketing and use as condition for filing a generally recognized as safe and effective request
(A) In generalIn response to a request under this section that a drug described in subparagraph (B) be generally recognized as safe and effective, the Secretary—
(i) may file such request, if the request includes information specified under subparagraph (C) with respect to safe nonprescription marketing and use of such drug; or
(ii) if the request fails to include information specified under subparagraph (C), shall refuse to file such request and require that nonprescription marketing of the drug be pursuant to a new drug application as described in subparagraph (D).
(B) Drug describedA drug described in this subparagraph is a nonprescription drug which contains an active ingredient not previously incorporated in a drug—
(i) specified in subsection (a)(1), (a)(2), or (a)(3);
(ii) subject to a final order under this section; or
(iii) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title).
(C) Information demonstrating prima facie safe nonprescription marketing and useInformation specified in this subparagraph, with respect to a request described in subparagraph (A)(i), is—
(i) information sufficient for a prima facie demonstration that the drug subject to such request has a verifiable history of being marketed and safely used by consumers in the United States as a nonprescription drug under comparable conditions of use;
(ii) if the drug has not been previously marketed in the United States as a nonprescription drug, information sufficient for a prima facie demonstration that the drug was marketed and safely used under comparable conditions of marketing and use in a country listed in section 382(b)(1)(A) of this title or designated by the Secretary in accordance with section 382(b)(1)(B) of this title—(I) for such period as needed to provide reasonable assurances concerning the safe nonprescription use of the drug; and(II) during such time was subject to sufficient monitoring by a regulatory body considered acceptable by the Secretary for such monitoring purposes, including for adverse events associated with nonprescription use of the drug; or
(iii) if the Secretary determines that information described in clause (i) or (ii) is not needed to provide a prima facie demonstration that the drug can be safely marketed and used as a nonprescription drug, such other information the Secretary determines is sufficient for such purposes.
(D) Marketing pursuant to new drug applicationIn the case of a request described in subparagraph (A)(ii), the drug subject to such request may be resubmitted for filing only if—
(i) the drug is marketed as a nonprescription drug, under conditions of use comparable to the conditions specified in the request, for such period as the Secretary determines appropriate (not to exceed 5 consecutive years) pursuant to an application approved under section 355 of this title; and
(ii) during such period, 1,000,000 retail packages of the drug, or an equivalent quantity as determined by the Secretary, were distributed for retail sale, as determined in such manner as the Secretary finds appropriate.
(E) Rule of application
(7) Packaging
(8) Final and tentative final monographs for category I drugs deemed final administrative orders
(A) In general
(B) Monographs describedFor purposes of subparagraph (A), a final monograph or tentative final monograph is described in this subparagraph if it—
(i) establishes conditions of use for a drug described in paragraph (1) or (2) of subsection (a); and
(ii) represents the most recently promulgated version of such conditions, including as modified, in whole or in part, by any proposed or final rule.
(C) Deemed orders include harmonizing technical amendments
(c) Procedure for minor changes
(1) In generalMinor changes in the dosage form of a drug that is described in paragraph (1) or (2) of subsection (a) or the subject of an order issued under subsection (b) may be made by a requestor without the issuance of an order under subsection (b) if—
(A) the requestor maintains such information as is necessary to demonstrate that the change—
(i) will not affect the safety or effectiveness of the drug; and
(ii) will not materially affect the extent of absorption or other exposure to the active ingredient in comparison to a suitable reference product; and
(B) the change is in conformity with the requirements of an applicable administrative order issued by the Secretary under paragraph (3).
(2) Additional information
(A) Access to records
(B) Insufficient informationIf the Secretary determines that the information contained in such records is not sufficient to demonstrate that the change does not affect the safety or effectiveness of the drug or materially affect the extent of absorption or other exposure to the active ingredient, the Secretary—
(i) may so inform the sponsor of the drug in writing; and
(ii) if the Secretary so informs the sponsor, shall provide the sponsor of the drug with a reasonable opportunity to provide additional information.
(C) Failure to submit sufficient informationIf the sponsor fails to provide such additional information within a time prescribed by the Secretary, or if the Secretary determines that such additional information does not demonstrate that the change does not—
(i) affect the safety or effectiveness of the drug; or
(ii) materially affect the extent of absorption or other exposure to the active ingredient in comparison to a suitable reference product,
the drug as modified is a new drug under section 321(p) of this title and shall be deemed to be misbranded under section 352(ee) of this title.
(3) Determining whether a change will affect safety or effectiveness
(A) In general
(B) Standard practices
(d) Confidentiality of information submitted to the Secretary
(1) In general
(2) Public availability
(A) In generalExcept as provided in subparagraph (B), the Secretary shall—
(i) make any information submitted by a requestor in support of a request under subsection (b)(5)(A) available to the public not later than the date on which the proposed order is issued; and
(ii) make any information submitted by any other person with respect to an order requested (or initiated by the Secretary) under subsection (b), available to the public upon such submission.
(B) Limitations on public availabilityInformation described in subparagraph (A) shall not be made public if—
(i) the information pertains to pharmaceutical quality information, unless such information is necessary to establish standards under which a drug is generally recognized as safe and effective under section 321(p)(1) of this title;
(ii) the information is submitted in a requestor-initiated request, but the requestor withdraws such request, in accordance with withdrawal procedures established by the Secretary, before the Secretary issues the proposed order;
(iii) the Secretary requests and obtains the information under subsection (c) and such information is not submitted in relation to an order under subsection (b); or
(iv) the information is of the type contained in raw datasets.
(e) Updates to drug listing information
(f) Approvals under section 355 of this title
(g) Public availability of administrative ordersThe Secretary shall establish, maintain, update (as determined necessary by the Secretary but no less frequently than annually), and make publicly available, with respect to orders issued under this section—
(1) a repository of each final order and interim final order in effect, including the complete text of the order; and
(2) a listing of all orders proposed and under development under subsection (b)(2), including—
(A) a brief description of each such order; and
(B) the Secretary’s expectations, if resources permit, for issuance of proposed orders over a 3-year period.
(h) Development advice to sponsors or requestors
(i) Participation of multiple sponsors or requestors
(j) Electronic format
(k) Effect on existing regulations governing nonprescription drugs
(1) Regulations of general applicability to nonprescription drugs
(2) Regulations establishing requirements for specific nonprescription drugs
(A) The provisions of section 310.545 of title 21, Code of Federal Regulations, as in effect on the day before March 27, 2020, shall be deemed to be a final order under subsection (b).
(B) Regulations in effect on the day before March 27, 2020, establishing requirements for specific nonprescription drugs marketed pursuant to this section (including such requirements in parts 201 and 250 of title 21, Code of Federal Regulations), shall be deemed to be final orders under subsection (b), only as they apply to drugs—
(i) subject to paragraph (1), (2), (3), or (4) of subsection (a); or
(ii) otherwise subject to an order under this section.
(3) Withdrawal of regulations
(l) GuidanceThe Secretary shall issue guidance that specifies—
(1) the procedures and principles for formal meetings between the Secretary and sponsors or requestors for drugs subject to this section;
(2) the format and span of data submissions to the Secretary under this section;
(3) the format of electronic submissions to the Secretary under this section;
(4) consolidated proceedings for appeal and the procedures for such proceedings where appropriate; and
(5) for minor changes in drugs, recommendations on how to comply with the requirements in orders issued under subsection (c)(3).
(m) Rule of construction
(1) In generalThis section shall not affect the treatment or status of a nonprescription drug—
(A) that is marketed without an application approved under section 355 of this title as of March 27, 2020;
(B) that is not subject to an order issued under this section; and
(C) to which paragraph (1), (2), (3), (4), or (5) of subsection (a) do not apply.
(2) Treatment of products previously found to be subject to time and extent requirements
(A) Notwithstanding subsection (a), a drug described in subparagraph (B) may only be lawfully marketed, without an application approved under section 355 of this title, pursuant to an order issued under this section.
(B) A drug described in this subparagraph is a drug which, prior to March 27, 2020, the Secretary determined in a proposed or final rule to be ineligible for review under the OTC drug review (as such phrase “OTC drug review” was used in section 330.14 of title 21, Code of Federal Regulations, as in effect on the day before March 27, 2020).
(3) Preservation of authority
(A) Nothing in paragraph (1) shall be construed to preclude or limit the applicability of any provision of this chapter other than this section.
(B) Nothing in subsection (a) shall be construed to prohibit the Secretary from issuing an order under this section finding a drug to be not generally recognized as safe and effective under section 321(p)(1) of this title, as the Secretary determines appropriate.
(n) Investigational new drugs
(o) Inapplicability of Paperwork Reduction Act
(p) Inapplicability of notice and comment rulemaking and other requirements
(q) DefinitionsIn this section:
(1) The term “nonprescription drug” refers to a drug not subject to the requirements of section 353(b)(1) of this title.
(2) The term “sponsor” refers to any person marketing, manufacturing, or processing a drug that—
(A) is listed pursuant to section 360(j) of this title; and
(B) is or will be subject to an administrative order under this section of the Food and Drug Administration.
(3) The term “requestor” refers to any person or group of persons marketing, manufacturing, processing, or developing a drug.
(June 25, 1938, ch. 675, § 505G, as added Pub. L. 116–136, div. A, title III, § 3851(a), Mar. 27, 2020, 134 Stat. 435.)

CITE AS: 21 USC 355h

§ 356. Expedited approval of drugs for serious or life-threatening diseases or conditions
(a) Designation of a drug as a breakthrough therapy
(1) In general
(2) Request for designation
(3) Designation
(A) In general
(B) ActionsThe actions to expedite the development and review of an application under subparagraph (A) may include, as appropriate—
(i) holding meetings with the sponsor and the review team throughout the development of the drug;
(ii) providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable;
(iii) involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review;
(iv) assigning a cross-disciplinary project lead for the Food and Drug Administration review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor; and
(v) taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment.
(b) Designation of drug as fast track product
(1) In general
(2) Request for designation
(3) Designation
(c) Accelerated approval of a drug for a serious or life-threatening disease or condition, including a fast track product
(1) In general
(A) Accelerated approval
(B) Evidence
(2) Limitation
(A) In generalApproval of a product under this subsection may be subject to 1 or both of the following requirements:
(i) That the sponsor conduct an appropriate postapproval study or studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit.
(ii) That the sponsor submit copies of all promotional materials related to the product during the preapproval review period and, following approval and for such period thereafter as the Secretary determines to be appropriate, at least 30 days prior to dissemination of the materials.
(B) Studies not required
(C) Postapproval study conditions
(D) Studies begun before approval
(3) Expedited withdrawal of approval
(A) In generalThe Secretary may withdraw approval of a product approved under accelerated approval using expedited procedures described in subparagraph (B) if—
(i) the sponsor fails to conduct any required postapproval study of the product with due diligence, including with respect to conditions specified by the Secretary under paragraph (2)(C);
(ii) a study required to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit of the product fails to verify and describe such effect or benefit;
(iii) other evidence demonstrates that the product is not shown to be safe or effective under the conditions of use; or
(iv) the sponsor disseminates false or misleading promotional materials with respect to the product.
(B) Expedited procedures describedExpedited procedures described in this subparagraph shall consist of, prior to the withdrawal of accelerated approval—
(i) providing the sponsor with—(I) due notice;(II) an explanation for the proposed withdrawal;(III) an opportunity for a meeting with the Commissioner or the Commissioner’s designee; and(IV) an opportunity for written appeal to—(aa) the Commissioner; or(bb) a designee of the Commissioner who has not participated in the proposed withdrawal of approval (other than a meeting pursuant to subclause (III)) and is not subordinate of an individual (other than the Commissioner) who participated in such proposed withdrawal;
(ii) providing an opportunity for public comment on the proposal to withdraw approval;
(iii) the publication of a summary of the public comments received, and the Secretary’s response to such comments, on the website of the Food and Drug Administration; and
(iv) convening and consulting an advisory committee on issues related to the proposed withdrawal, if requested by the sponsor and if no such advisory committee has previously advised the Secretary on such issues with respect to the withdrawal of the product prior to the sponsor’s request.
(d) Review of incomplete applications for approval of a fast track product
(1) In generalIf the Secretary determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may be effective, the Secretary shall evaluate for filing, and may commence review of portions of, an application for the approval of the product before the sponsor submits a complete application. The Secretary shall commence such review only if the applicant—
(A) provides a schedule for submission of information necessary to make the application complete; and
(B) pays any fee that may be required under section 379h of this title.
(2) Exception
(e) Construction
(1) Purpose
(2) Construction
(f) Awareness effortsThe Secretary shall—
(1) develop and disseminate to physicians, patient organizations, pharmaceutical and biotechnology companies, and other appropriate persons a description of the provisions of this section applicable to breakthrough therapies, accelerated approval, and and 1
1 So in original.
fast track products; and
(2) establish a program to encourage the development of surrogate and clinical endpoints, including biomarkers, and other scientific methods and tools that can assist the Secretary in determining whether the evidence submitted in an application is reasonably likely to predict clinical benefit for serious or life-threatening conditions for which significant unmet medical needs exist.
(g) Regenerative advanced therapy
(1) In general
(2) CriteriaA drug is eligible for designation as a regenerative advanced therapy under this subsection if—
(A) the drug is a regenerative medicine therapy (as defined in paragraph (8));
(B) the drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
(C) preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such a disease or condition.
(3) Request for designation
(4) Designation
(5) Actions
(6) Access to expedited approval pathwaysAn application for a regenerative advanced therapy under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] may be—
(A) eligible for priority review, as described in the Manual of Policies and Procedures of the Food and Drug Administration and goals identified in the letters described in section 101(b) of the Prescription Drug User Fee Amendments of 2012; and
(B) eligible for accelerated approval under subsection (c), as agreed upon pursuant to subsection (a)(3)(B), through, as appropriate—
(i) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit; or
(ii) reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites, as appropriate.
(7) Postapproval requirementsThe sponsor of a regenerative advanced therapy that is granted accelerated approval and is subject to the postapproval requirements under subsection (c) may, as appropriate, fulfill such requirements, as the Secretary may require, through—
(A) the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records;
(B) the collection of larger confirmatory data sets, as agreed upon pursuant to subsection (a)(3)(B); or
(C) postapproval monitoring of all patients treated with such therapy prior to approval of the therapy.
(8) Definition
(h) Limited population pathway for antibacterial and antifungal drugs
(1) In generalThe Secretary may approve an antibacterial or antifungal drug, alone or in combination with one or more other drugs, as a limited population drug pursuant to this subsection only if—
(A) the drug is intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs;
(B) the standards for approval under section 355(c) and (d) of this title, or the standards for licensure under section 351 of the Public Health Service Act [42 U.S.C. 262], as applicable, are met; and
(C) the Secretary receives a written request from the sponsor to approve the drug as a limited population drug pursuant to this subsection.
(2) Benefit-risk consideration
(3) Additional requirementsA drug approved under this subsection shall be subject to the following requirements, in addition to any other applicable requirements of this chapter:
(A) LabelingTo indicate that the safety and effectiveness of a drug approved under this subsection has been demonstrated only with respect to a limited population—
(i) all labeling and advertising of an antibacterial or antifungal drug approved under this subsection shall contain the statement “Limited Population” in a prominent manner and adjacent to, and not more prominent than—(I) the proprietary name of such drug, if any; or(II) if there is no proprietary name, the established name of the drug, if any, as defined in section 353(e)(3) of this title, or, in the case of a drug that is a biological product, the proper name, as defined by regulation; and
(ii) the prescribing information for the drug required by section 201.57 of title 21, Code of Federal Regulations (or any successor regulation) shall also include the following statement: “This drug is indicated for use in a limited and specific population of patients.”.
(B) Promotional material
(4) Other programs
(5) Guidance
(6) Advice
(7) Termination of limitations
(8) Rules of construction
(9) Reporting and accountability
(A) Biennial reporting
(B) GAO report
(June 25, 1938, ch. 675, § 506, as added Pub. L. 105–115, title I, § 112(a), Nov. 21, 1997, 111 Stat. 2309; amended Pub. L. 112–144, title VIII, § 803, title IX, §§ 901(b), 902(a), July 9, 2012, 126 Stat. 1079, 1083, 1086; Pub. L. 114–255, div. A, title III, §§ 3033(a), (c), 3042, Dec. 13, 2016, 130 Stat. 1101, 1103, 1112; Pub. L. 117–328, div. FF, title III, § 3210(a), Dec. 29, 2022, 136 Stat. 5822.)

CITE AS: 21 USC 356

§ 356–1. Accelerated approval of priority countermeasures
(a) In general
The Secretary of Health and Human Services may designate a priority countermeasure as a fast-track product pursuant to section 356 of this title or as a device granted review priority pursuant to section 360e(d)(5) 1
1 See References in Text note below.
of this title. Such a designation may be made prior to the submission of—
(1) a request for designation by the sponsor or applicant; or
(2) an application for the investigation of the drug under section 355(i) of this title or section 262(a)(3) of title 42.
Nothing in this subsection shall be construed to prohibit a sponsor or applicant from declining such a designation.
(b) Use of animal trials
(c) Priority review of drugs and biological products
(d) Definitions
For purposes of this title: 1
(1) The term “priority countermeasure” has the meaning given such term in section 247d–6(h)(4) 1 of title 42.
(2) The term “priority drugs or biological products” means a drug or biological product that is the subject of a drug or biologics application referred to in section 101(4) of the Food and Drug Administration Modernization Act of 1997.
(Pub. L. 107–188, title I, § 122, June 12, 2002, 116 Stat. 613.)

CITE AS: 21 USC 356-1

§ 356–2. Accelerated approval Council
(1) In general
(2) Membership
The members of the Council shall consist of the following senior officials, or a designee of such official, from the Food and Drug Administration and relevant Centers:
(A) The Director of the Center for Drug Evaluation and Research.
(B) The Director of the Center for Biologics Evaluation and Research.
(C) The Director of the Oncology Center of Excellence.
(D) The Director of the Office of New Drugs.
(E) The Director of the Office of Orphan Products Development.
(F) The Director of the Office of Tissues and Advanced Therapies.
(G) The Director of the Office of Medical Policy.
(H) At least 3 directors of review divisions or offices overseeing products approved under accelerated approval, including at least one director within the Office of Neuroscience.
(3) Duties of the Council
(A) Meetings
(B) Policy development
The Council shall directly engage with product review teams to support the consistent and appropriate use of accelerated approval across the Food and Drug Administration. Such engagement may include—
(i) developing guidance for Food and Drug Administration staff and best practices for, and across, product review teams, including with respect to communication between sponsors and the Food and Drug Administration and the review of products under accelerated approval;
(ii) providing training for product review teams; and
(iii) advising review divisions on best practices with respect to product-specific development, review, and withdrawal of products under accelerated approval.
(4) Publication of a report
(Pub. L. 117–328, div. FF, title III, § 3210(e), Dec. 29, 2022, 136 Stat. 5824.)

CITE AS: 21 USC 356-2

§ 356a. Manufacturing changes
(a) In general
With respect to a drug for which there is in effect an approved application under section 355 or 360b of this title or a license under section 262 of title 42, a change from the manufacturing process approved pursuant to such application or license may be made, and the drug as made with the change may be distributed, if—
(1) the holder of the approved application or license (referred to in this section as a “holder”) has validated the effects of the change in accordance with subsection (b); and
(2)
(A) in the case of a major manufacturing change, the holder has complied with the requirements of subsection (c); or
(B) in the case of a change that is not a major manufacturing change, the holder complies with the applicable requirements of subsection (d).
(b) Validation of effects of changes
(c) Major manufacturing changes
(1) Requirement of supplemental application
(2) Changes qualifying as major changes
For purposes of subsection (a)(2)(A), a major manufacturing change is a manufacturing change that is determined by the Secretary to have substantial potential to adversely affect the identity, strength, quality, purity, or potency of the drug as they may relate to the safety or effectiveness of a drug. Such a change includes a change that—
(A) is made in the qualitative or quantitative formulation of the drug involved or in the specifications in the approved application or license referred to in subsection (a) for the drug (unless exempted by the Secretary by regulation or guidance from the requirements of this subsection);
(B) is determined by the Secretary by regulation or guidance to require completion of an appropriate clinical study demonstrating equivalence of the drug to the drug as manufactured without the change; or
(C) is another type of change determined by the Secretary by regulation or guidance to have a substantial potential to adversely affect the safety or effectiveness of the drug.
(d) Other manufacturing changes
(1) In general
For purposes of subsection (a)(2)(B), the Secretary may regulate drugs made with manufacturing changes that are not major manufacturing changes as follows:
(A) The Secretary may in accordance with paragraph (2) authorize holders to distribute such drugs without submitting a supplemental application for such changes.
(B) The Secretary may in accordance with paragraph (3) require that, prior to the distribution of such drugs, holders submit to the Secretary supplemental applications for such changes.
(C) The Secretary may establish categories of such changes and designate categories to which subparagraph (A) applies and categories to which subparagraph (B) applies.
(2) Changes not requiring supplemental application
(A) Submission of report
(B) Authority regarding annual reports
(3) Changes requiring supplemental application
(A) Submission of supplemental application
(B) Authority for distribution
In the case of a manufacturing change to which paragraph (1)(B) applies:
(i) The holder involved may commence distribution of the drug involved 30 days after the Secretary receives the supplemental application under such paragraph, unless the Secretary notifies the holder within such 30-day period that prior approval of the application is required before distribution may be commenced.
(ii) The Secretary may designate a category of such changes for the purpose of providing that, in the case of a change that is in such category, the holder involved may commence distribution of the drug involved upon the receipt by the Secretary of a supplemental application for the change.
(iii) If the Secretary disapproves the supplemental application, the Secretary may order the manufacturer to cease the distribution of the drugs that have been made with the manufacturing change.
(June 25, 1938, ch. 675, § 506A, as added Pub. L. 105–115, title I, § 116(a), Nov. 21, 1997, 111 Stat. 2313.)

CITE AS: 21 USC 356a

§ 356b. Reports of postmarketing studies
(a) Submission
(1) In general
(2) Accelerated approval
(3) Agreements prior to effective date
(b) Consideration of information as public information
Any information pertaining to a report described in subsection (a) shall be considered to be public information to the extent that the information is necessary—
(1) to identify the sponsor; and
(2) to establish the status of a study described in subsection (a) and the reasons, if any, for any failure to carry out the study.
(c) Status of studies and reports
The Secretary shall annually develop and publish in the Federal Register a report that provides information on the status of the postmarketing studies—
(1) that sponsors have entered into agreements to conduct; and
(2) for which reports have been submitted under subsection (a)(1).
(d) Disclosure
(e) Notification
(June 25, 1938, ch. 675, § 506B, as added Pub. L. 105–115, title I, § 130(a), Nov. 21, 1997, 111 Stat. 2331; amended Pub. L. 107–188, title V, § 506, June 12, 2002, 116 Stat. 693; Pub. L. 112–144, title IX, § 902(c), July 9, 2012, 126 Stat. 1088; Pub. L. 117–328, div. FF, title III, § 3210(b), Dec. 29, 2022, 136 Stat. 5823.)

CITE AS: 21 USC 356b

§ 356c. Discontinuance or interruption in the production of life-saving drugs
(a) In generalA manufacturer of a drug—
(1) that is—
(A) life-supporting;
(B) life-sustaining; or
(C) intended for use in the prevention or treatment of a debilitating disease or condition, including any such drug used in emergency medical care or during surgery or any such drug that is critical to the public health during a public health emergency declared by the Secretary under section 247d of title 42; and
(2) that is not a radio pharmaceutical drug product or any other product as designated by the Secretary,
shall notify the Secretary, in accordance with subsection (b), of a permanent discontinuance in the manufacture of the drug or an interruption of the manufacture of the drug that is likely to lead to a meaningful disruption in the supply of that drug in the United States, or a permanent discontinuance in the manufacture of an active pharmaceutical ingredient or an interruption in the manufacture of the active pharmaceutical ingredient of such drug that is likely to lead to a meaningful disruption in the supply of the active pharmaceutical ingredient of such drug, and the reasons for such discontinuance or interruption. Notification under this subsection shall include disclosure of reasons for the discontinuation or interruption, and if applicable, an active pharmaceutical ingredient is a reason for, or risk factor in, such discontinuation or interruption, the source of the active pharmaceutical ingredient and any alternative sources for the active pharmaceutical ingredient known by the manufacturer; whether any associated device used for preparation or administration included in the drug is a reason for, or a risk factor in, such discontinuation or interruption; the expected duration of the interruption; and such other information as the Secretary may require.
(b) TimingA notice required under subsection (a) shall be submitted to the Secretary—
(1) at least 6 months prior to the date of the discontinuance or interruption; or
(2) if compliance with paragraph (1) is not possible, as soon as practicable.
(c) Distribution
(d) Confidentiality
(e) Coordination with Attorney GeneralNot later than 30 days after the receipt of a notification described in subsection (a), the Secretary shall—
(1) determine whether the notification pertains to a controlled substance subject to a production quota under section 826 of this title; and
(2) if necessary, as determined by the Secretary—
(A) notify the Attorney General that the Secretary has received such a notification;
(B) request that the Attorney General increase the aggregate and individual production quotas under section 826 of this title applicable to such controlled substance and any ingredient therein to a level the Secretary deems necessary to address a shortage of a controlled substance based on the best available market data; and
(C) if the Attorney General determines that the level requested is not necessary to address a shortage of a controlled substance, the Attorney General shall provide to the Secretary a written response detailing the basis for the Attorney General’s determination.
The Secretary shall make the written response provided under subparagraph (C) available to the public on the Internet Web site of the Food and Drug Administration.
(f) Failure to meet requirementsIf a person fails to submit information required under subsection (a) in accordance with subsection (b)—
(1) the Secretary shall issue a letter to such person informing such person of such failure;
(2) not later than 30 calendar days after the issuance of a letter under paragraph (1), the person who receives such letter shall submit to the Secretary a written response to such letter setting forth the basis for noncompliance and providing information required under subsection (a); and
(3) not later than 45 calendar days after the issuance of a letter under paragraph (1), the Secretary shall make such letter and any response to such letter under paragraph (2) available to the public on the Internet Web site of the Food and Drug Administration, with appropriate redactions made to protect information described in subsection (d), except that, if the Secretary determines that the letter under paragraph (1) was issued in error or, after review of such response, the person had a reasonable basis for not notifying as required under subsection (a), the requirements of this paragraph shall not apply.
(g) Expedited inspections and reviewsIf, based on notifications described in subsection (a) or any other relevant information, the Secretary concludes that there is, or is likely to be, a drug shortage of a drug described in subsection (a), the Secretary shall, as appropriate—
(1) prioritize and expedite the review of a supplement to a new drug application submitted under section 355(b) of this title, an abbreviated new drug application submitted under section 355(j) of this title, or a supplement to such an application submitted under section 355(j) of this title, that could help mitigate or prevent such shortage; or
(2) prioritize and expedite an inspection or reinspection of an establishment that could help mitigate or prevent such drug shortage.
(h) DefinitionsFor purposes of this section—
(1) the term “drug”—
(A) means a drug (as defined in section 321(g) of this title) that is intended for human use and that is subject to section 353(b)(1) of this title; and
(B) does not include biological products (as defined in section 262 of title 42), unless otherwise provided by the Secretary in the regulations promulgated under subsection (i);
(2) the term “drug shortage” or “shortage”, with respect to a drug, means a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug; and
(3) the term “meaningful disruption”—
(A) means a change in production that is reasonably likely to lead to a reduction in the supply of a drug by a manufacturer that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product; and
(B) does not include interruptions in manufacturing due to matters such as routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time.
(i) Regulations
(1) In general
(2) Contents
(3) Inclusion of biological products
(A) In general
(B) Rule for vaccinesIf the Secretary applies this section to vaccines pursuant to subparagraph (A), the Secretary shall—
(i) consider whether the notification requirement under subsection (a) may be satisfied by submitting a notification to the Centers for Disease Control and Prevention under the vaccine shortage notification program of such Centers; and
(ii) explain the determination made by the Secretary under clause (i) in the regulation.
(4) ProcedureIn promulgating a regulation implementing this section, the Secretary shall—
(A) issue a notice of proposed rulemaking that includes the proposed regulation;
(B) provide a period of not less than 60 days for comments on the proposed regulation; and
(C) publish the final regulation not less than 30 days before the regulation’s effective date.
(5) Restrictions
(j) Risk management plans
(June 25, 1938, ch. 675, § 506C, as added Pub. L. 105–115, title I, § 131(a), Nov. 21, 1997, 111 Stat. 2332; amended Pub. L. 112–144, title X, § 1001(a), July 9, 2012, 126 Stat. 1099; Pub. L. 114–255, div. A, title III, § 3101(a)(2)(E), Dec. 13, 2016, 130 Stat. 1153; Pub. L. 116–136, div. A, title III, §§ 3111–3112(b), Mar. 27, 2020, 134 Stat. 361, 362; Pub. L. 117–328, div. FF, title II, § 2515(a)(1), (b)(1), Dec. 29, 2022, 136 Stat. 5806.)

CITE AS: 21 USC 356c

§ 356c–1. Annual reporting on drug shortages
(a) Annual reports to CongressNot later than March 31 of each calendar year, the Secretary shall submit to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate a report, with respect to the preceding calendar year, on drug shortages that—
(1) specifies the number of manufacturers that submitted a notification to the Secretary under section 356c(a) of this title during such calendar year;
(2) describes the communication between the field investigators of the Food and Drug Administration and the staff of the Center for Drug Evaluation and Research’s Office of Compliance and Drug Shortage Program, including the Food and Drug Administration’s procedures for enabling and ensuring such communication;
(3) describes the coordination and alignment activities undertaken pursuant to section 356d(g) of this title;
(4) provides the number of reports that were required under section 374(b)(2) of this title to be sent to the appropriate offices of the Food and Drug Administration with expertise regarding drug shortages, and the number of such reports that were sent;
(5)
(A) lists the major actions taken by the Secretary to prevent or mitigate the drug shortages described in paragraph (9);
(B) in the list under subparagraph (A), includes—
(i) the number of applications and supplements for which the Secretary expedited review under section 356c(g)(1) of this title during such calendar year; and
(ii) the number of establishment inspections or reinspections that the Secretary expedited under section 356c(g)(2) of this title during such calendar year;
(6) describes the coordination between the Food and Drug Administration and the Drug Enforcement Administration on efforts to prevent or alleviate drug shortages;
(7) identifies the number of and describes the instances in which the Food and Drug Administration exercised regulatory flexibility and discretion to prevent or alleviate a drug shortage;
(8) lists the names of manufacturers that were issued letters under section 356c(f) of this title; and
(9) specifies the number of drug shortages occurring during such calendar year, as identified by the Secretary.
(b) Trend analysis
(c) Definition
(June 25, 1938, ch. 675, § 506C–1, as added Pub. L. 112–144, title X, § 1002, July 9, 2012, 126 Stat. 1102; amended Pub. L. 114–255, div. A, title III, § 3101(a)(2)(F), Dec. 13, 2016, 130 Stat. 1153; Pub. L. 117–328, div. FF, title III, § 3616(b)(1), Dec. 29, 2022, 136 Stat. 5875.)

CITE AS: 21 USC 356c-1

§ 356d. Coordination; task force and strategic plan
(a) Task force and strategic plan
(1) In general
(A) Task force
(B) Strategic planThe strategic plan described in subparagraph (A) shall include—
(i) plans for enhanced interagency and intra-agency coordination, communication, and decisionmaking;
(ii) plans for ensuring that drug shortages are considered when the Secretary initiates a regulatory action that could precipitate a drug shortage or exacerbate an existing drug shortage;
(iii) plans for effective communication with outside stakeholders, including who the Secretary should alert about potential or actual drug shortages, how the communication should occur, and what types of information should be shared;
(iv) plans for considering the impact of drug shortages on research and clinical trials; and
(v) an examination of whether to establish a “qualified manufacturing partner program”, as described in subparagraph (C).
(C) Description of programIn conducting the examination of a “qualified manufacturing partner program” under subparagraph (B)(v), the Secretary—
(i) shall take into account that—(I) a “qualified manufacturer”, for purposes of such program, would need to have the capability and capacity to supply products determined or anticipated to be in shortage; and(II) in examining the capability and capacity to supply products in shortage, the “qualified manufacturer” could have a site that manufactures a drug listed under section 356e of this title or have the capacity to produce drugs in response to a shortage within a rapid timeframe; and
(ii) shall examine whether incentives are necessary to encourage the participation of “qualified manufacturers” in such a program.
(D) Consultation
(2) TimingNot later than 1 year after July 9, 2012, the task force shall—
(A) publish the strategic plan described in paragraph (1); and
(B) submit such plan to Congress.
(b) Communication
(c) Action
(d) Reporting by other entities
(e) Review and constructionNo determination, finding, action, or omission of the Secretary under this section shall—
(1) be subject to judicial review; or
(2) be construed to establish a defense to an enforcement action by the Secretary.
(f) Temporary sunset
(g) CoordinationThe Secretary shall ensure timely and effective internal coordination and alignment among the field investigators of the Food and Drug Administration and the staff of the Center for Drug Evaluation and Research’s Office of Compliance and Drug Shortage Program regarding—
(1) the reviews of reports shared pursuant to section 374(b)(2) of this title; and
(2) any feedback or corrective or preventive actions in response to such reports.
(June 25, 1938, ch. 675, § 506D, as added Pub. L. 112–144, title X, § 1003, July 9, 2012, 126 Stat. 1103; amended Pub. L. 117–328, div. FF, title III, § 3616(a), Dec. 29, 2022, 136 Stat. 5874.)

CITE AS: 21 USC 356d

§ 356e. Drug shortage list
(a) Establishment
(b) ContentsFor each drug on such list, the Secretary shall include the following information:
(1) The name of the drug in shortage, including the National Drug Code number for such drug.
(2) The name of each manufacturer of such drug.
(3) The reason for the shortage, as determined by the Secretary, selecting from the following categories:
(A) Requirements related to complying with good manufacturing practices.
(B) Regulatory delay.
(C) Shortage of an active ingredient.
(D) Shortage of an inactive ingredient component.
(E) Discontinuance of the manufacture of the drug.
(F) Delay in shipping of the drug.
(G) Demand increase for the drug.
(4) The estimated duration of the shortage as determined by the Secretary.
(c) Public availability
(1) In general
(2) Trade secrets and confidential information
(3) Public health exception
(d) Interagency notification
(June 25, 1938, ch. 675, § 506E, as added Pub. L. 112–144, title X, § 1004, July 9, 2012, 126 Stat. 1104; amended Pub. L. 114–255, div. A, title III, § 3101(a)(2)(G), Dec. 13, 2016, 130 Stat. 1153; Pub. L. 116–136, div. A, title III, § 3112(c), Mar. 27, 2020, 134 Stat. 362.)

CITE AS: 21 USC 356e

§ 356f. Hospital repackaging of drugs in shortage
(a) Definitions
In this section:
(1) Drug
(2) Health system
(3) Repackage
For the purposes of this section only, the term “repackage”, with respect to a drug, means to divide the volume of a drug into smaller amounts in order to—
(A) extend the supply of a drug in response to the placement of the drug on a drug shortage list under section 356e of this title; and
(B) facilitate access to the drug by hospitals within the same health system.
(b) Exclusion from registration
Notwithstanding any other provision of this chapter, a hospital shall not be considered an establishment for which registration is required under section 360 of this title solely because it repackages a drug and transfers it to another hospital within the same health system in accordance with the conditions in subsection (c)—
(1) during any period in which the drug is listed on the drug shortage list under section 356e of this title; or
(2) during the 60-day period following any period described in paragraph (1).
(c) Conditions
Subsection (b) shall only apply to a hospital, with respect to the repackaging of a drug for transfer to another hospital within the same health system, if the following conditions are met:
(1) Drug for intrasystem use only
(2) Compliance with State rules
(d) Termination
(June 25, 1938, ch. 675, § 506F, as added Pub. L. 112–144, title X, § 1007, July 9, 2012, 126 Stat. 1106.)

CITE AS: 21 USC 356f

§ 356g. Standards for regenerative medicine and regenerative advanced therapies
(a) In general
(b) Activities
(1) In general
In carrying out this section, the Secretary shall continue to—
(A) identify opportunities to help advance the development of regenerative medicine therapies and regenerative advanced therapies;
(B) identify opportunities for the development of laboratory regulatory science research and documentary standards that the Secretary determines would help support the development, evaluation, and review of regenerative medicine therapies and regenerative advanced therapies through regulatory predictability; and
(C) work with stakeholders, such as those described in subsection (a), as appropriate, in the development of such standards.
(2) Regulations and guidance
(c) Definitions
(June 25, 1938, ch. 675, § 506G, as added Pub. L. 114–255, div. A, title III, § 3036, Dec. 13, 2016, 130 Stat. 1104; amended Pub. L. 115–52, title IX, § 901(b), Aug. 18, 2017, 131 Stat. 1076.)

CITE AS: 21 USC 356g

§ 356h. Competitive generic therapies
(a) In general
(b) Designation process
(1) Request
(2) Timing
(3) Criteria
(4) DesignationNot later than 60 calendar days after the receipt of a request under paragraph (1), the Secretary may—
(A) determine whether the drug that is the subject of the request meets the criteria described in paragraph (3); and
(B) if the Secretary finds that the drug meets such criteria, designate the drug as a competitive generic therapy.
(c) ActionsIn expediting the development and review of an application under subsection (a), the Secretary may, as requested by the applicant, take actions including the following:
(1) Hold meetings with the applicant and the review team throughout the development of the drug prior to submission of the application for such drug under section 355(j) of this title.
(2) Provide timely advice to, and interactive communication with, the applicant regarding the development of the drug to ensure that the development program to gather the data necessary for approval is as efficient as practicable.
(3) Involve senior managers and experienced review staff, as appropriate, in a collaborative, coordinated review of such application, including with respect to drug-device combination products and other complex products.
(4) Assign a cross-disciplinary project lead—
(A) to facilitate an efficient review of the development program and application, including manufacturing inspections; and
(B) to serve as a scientific liaison between the review team and the applicant.
(d) Reporting requirement
(e) DefinitionsIn this section:
(1) The term “generic drug” means a drug that is approved pursuant to section 355(j) of this title.
(2) The term “inadequate generic competition” means, with respect to a drug, there is not more than one approved drugs 1
1 So in original. Probably should be “drug”.
on the list of drugs described in section 355(j)(7)(A) of this title (not including drugs on the discontinued section of such list) that is—
(A) the reference listed drug; or
(B) a generic drug with the same reference listed drug as the drug for which designation as a competitive generic therapy is sought.
(3) The term “reference listed drug” means the listed drug (as such term is used in section 355(j) of this title) for the drug involved.
(June 25, 1938, ch. 675, § 506H, as added Pub. L. 115–52, title VIII, § 803(a), Aug. 18, 2017, 131 Stat. 1070.)

CITE AS: 21 USC 356h

§ 356i. Prompt reports of marketing status
(a) Notification of withdrawal
The holder of an application approved under subsection (c) or (j) of section 355 of this title or subsection (a) or (k) of section 262 of title 42 shall notify the Secretary in writing 180 days prior to withdrawing the approved drug from sale, or if 180 days is not practicable as soon as practicable but not later than the date of withdrawal. The holder shall include with such notice the—
(1) National Drug Code;
(2) identity of the drug by established name (or, in the case of a biological product, the proper name) and by proprietary name, if any;
(3) new drug application number, abbreviated application number, or biologics license application number;
(4) strength of the drug;
(5) date on which the drug is expected to no longer be available for sale; and
(6) reason for withdrawal of the drug.
(b) Notification of drug not available for sale
The holder of an application approved under subsection (c) or (j) of section 355 of this title or subsection (a) or (k) of section 262 of title 42 shall notify the Secretary in writing within 180 calendar days of the date of approval of the drug if the drug will not be available for sale within 180 calendar days of such date of approval. The holder shall include with such notice the—
(1) identity of the drug by established name (or, in the case of a biological product, the proper name) and by proprietary name, if any;
(2) new drug application number, abbreviated application number, or biologics license application number;
(3) strength of the drug;
(4) date on which the drug will be available for sale, if known; and
(5) reason for not marketing the drug after approval.
(c) Additional one-time report
Within 180 days of December 29, 2022, all holders of applications approved under subsection (a) or (k) of section 262 of title 42 shall review the information in the list published under section 262(k)(9)(A) of title 42 and shall submit a written notice to the Secretary—
(1) stating that all of the application holder’s biological products in the list published under such section 262(k)(9)(A) of title 42 that are not listed as discontinued are available for sale; or
(2) including the information required pursuant to subsection (a) or (b), as applicable, for each of the application holder’s biological products that are in the list published under such section 262(k)(9)(A) of title 42 and not listed as discontinued, but have been discontinued from sale or never have been available for sale.
(d) Failure to meet requirements
If a holder of an approved application fails to submit the information required under subsection (a), (b), or (c), the Secretary may—
(1) move the application holder’s drugs from the active section of the list published under section 355(j)(7)(A) of this title to the discontinued section of the list, except that the Secretary shall remove from the list in accordance with section 355(j)(7)(C) of this title drugs the Secretary determines have been withdrawn from sale for reasons of safety or effectiveness; and
(2) identify the application holder’s biological products as discontinued in the list published under section 262(k)(9)(A) of title 42, except that the Secretary shall remove from the list in accordance with section 262(k)(9)(B) of such title biological products for which the license has been revoked or suspended for reasons of safety, purity, or potency.
(e) Updates
(f) Limitation on use of notices
(June 25, 1938, ch. 675, § 506I, as added Pub. L. 115–52, title VIII, § 804, Aug. 18, 2017, 131 Stat. 1071; amended Pub. L. 117–328, div. FF, title III, § 3201, Dec. 29, 2022, 136 Stat. 5808.)

CITE AS: 21 USC 356i

§ 356j. Discontinuance or interruption in the production of medical devices
(a) In generalA manufacturer of a device that—
(1) is critical to public health during a public health emergency, including devices that are life-supporting, life-sustaining, or intended for use in emergency medical care or during surgery; or
(2) for which the Secretary determines that information on potential meaningful supply disruptions of such device is needed during, or in advance of, a public health emergency;
shall, during, or in advance of, a public health emergency declared by the Secretary under section 247d of title 42, notify the Secretary, in accordance with subsection (b), of a permanent discontinuance in the manufacture of the device (except for discontinuances as a result of an approved modification of the device) or an interruption of the manufacture of the device that is likely to lead to a meaningful disruption in the supply of that device in the United States, and the reasons for such discontinuance or interruption.
(b) TimingA notice required under subsection (a) shall be submitted to the Secretary—
(1) at least 6 months prior to the date of the discontinuance or interruption; or
(2) if compliance with paragraph (1) is not possible, as soon as practicable.
(c) Distribution
(1) Public availability
(2) Public health exception
(d) Confidentiality
(e) Failure to meet requirementsIf a person fails to submit information required under subsection (a) in accordance with subsection (b)—
(1) the Secretary shall issue a letter to such person informing such person of such failure;
(2) not later than 30 calendar days after the issuance of a letter under paragraph (1), the person who receives such letter shall submit to the Secretary a written response to such letter setting forth the basis for noncompliance and providing information required under subsection (a); and
(3) not later than 45 calendar days after the issuance of a letter under paragraph (1), the Secretary shall make such letter and any response to such letter under paragraph (2) available to the public on the internet website of the Food and Drug Administration, with appropriate redactions made to protect information described in subsection (d), except that, if the Secretary determines that the letter under paragraph (1) was issued in error or, after review of such response, the person had a reasonable basis for not notifying as required under subsection (a), the requirements of this paragraph shall not apply.
(f) Expedited inspections and reviewsIf, based on notifications described in subsection (a) or (h) or any other relevant information, the Secretary concludes that there is, or is likely to be, a shortage of an 1
1 So in original. Probably should be “a”.
device, the Secretary shall, as appropriate—
(1) prioritize and expedite the review of a submission under section 360c(f)(2) of this title, 360e of this title, review of a notification under section 360(k) of this title, or 360j(m) of this title for a device that could help mitigate or prevent such shortage; or
(2) prioritize and expedite an inspection or reinspection of an establishment that could help mitigate or prevent such shortage.
(g) Device shortage list
(1) Establishment
(2) ContentsFor each device included on the list under paragraph (1), the Secretary shall include the following information:
(A) The category or name of the device in shortage.
(B) The name of each manufacturer of such device.
(C) The reason for the shortage, as determined by the Secretary, selecting from the following categories:
(i) Requirements related to complying with good manufacturing practices.
(ii) Regulatory delay.
(iii) Shortage or discontinuance of a component or part.
(iv) Discontinuance of the manufacture of the device.
(v) Delay in shipping of the device.
(vi) Delay in sterilization of the device.
(vii) Demand increase for the device.
(viii) Facility closure.
(D) The estimated duration of the shortage as determined by the Secretary.
(3) Public availability
(A) In general
(B) Trade secrets and confidential information
(C) Public health exception
(h) Additional notifications
(i) Rule of construction
(j) DefinitionsIn this section:
(1) Meaningful disruptionThe term “meaningful disruption”—
(A) means a change in production that is reasonably likely to lead to a reduction in the supply of a device by a manufacturer that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product;
(B) does not include interruptions in manufacturing due to matters such as routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time, not to exceed 6 months;
(C) does not include interruptions in manufacturing of components or raw materials so long as such interruptions do not result in a shortage of the device and the manufacturer expects to resume operations in a reasonable period of time; and
(D) does not include interruptions in manufacturing that do not lead to a reduction in procedures or diagnostic tests associated with a medical device designed to perform more than one procedure or diagnostic test.
(2) Shortage
(June 25, 1938, ch. 675, § 506J, as added Pub. L. 116–136, div. A, title III, § 3121, Mar. 27, 2020, 134 Stat. 363; amended Pub. L. 117–328, div. FF, title II, § 2514(a), Dec. 29, 2022, 136 Stat. 5805.)

CITE AS: 21 USC 356j

§ 356k. Platform technologies
(a) In general
(b) CriteriaA platform technology incorporated within or utilized by a drug or biological product is eligible for designation as a designated platform technology under this section if—
(1) the platform technology is incorporated in, or utilized by, a drug approved under section 355 of this title or a biological product licensed under section 351 of the Public Health Service Act [42 U.S.C. 262];
(2) preliminary evidence submitted by the sponsor of the approved or licensed drug described in paragraph (1), or a sponsor that has been granted a right of reference to data submitted in the application for such drug, demonstrates that the platform technology has the potential to be incorporated in, or utilized by, more than one drug without an adverse effect on quality, manufacturing, or safety; and
(3) data or information submitted by the applicable person under paragraph (2) indicates that incorporation or utilization of the platform technology has a reasonable likelihood to bring significant efficiencies to the drug development or manufacturing process and to the review process.
(c) Request for designation
(d) Designation
(1) In general
(2) Designation
(3) Determination not to designate
(4) Revocation of designation
(5) Applicability
(e) ActionsThe Secretary may take actions to expedite the development and review of an application for a drug that incorporates or utilizes a designated platform technology, including—
(1) engaging in early interactions with the sponsor to discuss the use of the designated platform technology and what is known about such technology, including data previously submitted that is relevant to establishing, as applicable, safety or efficacy under section 355(b) of this title or safety, purity, or potency under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)];
(2) providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug that proposes to use the designated platform technology to ensure that the development program designed to gather data necessary for approval or licensure is as efficient as practicable, which may include holding meetings with the sponsor and the review team throughout the development of the drug; and
(3) considering inspectional findings, including prior findings, related to the manufacture of a drug that incorporates or utilizes the designated platform technology.
(f) Leveraging data from designated platform technologiesThe Secretary shall, consistent with applicable standards for approval, authorization, or licensure under this chapter and section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)], allow the sponsor of an application under section 355(b) of this title or section 351(a) of the Public Health Service Act or a request for emergency use authorization under section 360bbb–3 of this title, in order to support approval, licensure, or authorization, to reference or rely upon data and information within an application or request for a drug or biological product that incorporates or utilizes the same platform technology designated under subsection (d), provided that—
(1) such data and information was submitted by the same sponsor, pursuant to the application for the drug with respect to which designation of the designated platform technology under subsection (d) was granted; or
(2) the sponsor relying on such data and information received a right of reference to such data and information from the sponsor described in paragraph (1).
(g) Changes to a designated platform technology
(h) DefinitionsFor purposes of this section:
(1) The term “platform technology” means a well-understood and reproducible technology, which may include a nucleic acid sequence, molecular structure, mechanism of action, delivery method, vector, or a combination of any such technologies that the Secretary determines to be appropriate, that the sponsor demonstrates—
(A) is incorporated in or utilized by a drug or biological product and is essential to the structure or function of such drug or biological product;
(B) can be adapted for, incorporated into, or utilized by, more than one drug or biological product sharing common structural elements; and
(C) facilitates the manufacture or development of more than one drug or biological product through a standardized production or manufacturing process or processes.
(2) The term “designated platform technology” means a platform technology that is designated as a platform technology under subsection (d).
(i) Rule of constructionNothing in this section shall be construed to—
(1) alter the authority of the Secretary to approve drugs pursuant to section 505 of this Act [21 U.S.C. 355] or license biological products pursuant to section 351 of the Public Health Service Act [42 U.S.C. 262], including standards of evidence and applicable conditions for approval or licensure under the applicable Act; or
(2) confer any new rights with respect to the permissibility of a sponsor of an application for a drug product or biological product referencing information contained in another application submitted by the holder of an approved application under section 355(c) of this title or of a license under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)].
(June 25, 1938, ch. 675, § 506K, as added Pub. L. 117–328, div. FF, title II, § 2503(a), Dec. 29, 2022, 136 Stat. 5798.)

CITE AS: 21 USC 356k

§ 356l. Advanced manufacturing technologies designation program
(a) In general
(b) Designation processThe Secretary shall establish a process for the designation under this section of methods of manufacturing drugs, including biological products, and active pharmaceutical ingredients of such drugs, as advanced manufacturing technologies. A method of manufacturing, or a combination of manufacturing methods, is eligible for designation as an advanced manufacturing technology if such method or combination of methods incorporates a novel technology, or uses an established technique or technology in a novel way, that will substantially improve the manufacturing process for a drug while maintaining equivalent, or providing superior, drug quality, including by—
(1) reducing development time for a drug using the designated manufacturing method; or
(2) increasing or maintaining the supply of—
(A) a drug that is life-supporting, life-sustaining, or of critical importance to providing health care; or
(B) a drug that is on the drug shortage list under section 356e of this title.
(c) Evaluation and designation of an advanced manufacturing technology
(1) SubmissionA person who requests designation of a method of manufacturing as an advanced manufacturing technology under this section shall submit to the Secretary data or information demonstrating that the method of manufacturing meets the criteria described in subsection (b) in a particular context of use. The Secretary may facilitate the development and review of such data or information by—
(A) providing timely advice to, and interactive communication with, such person regarding the development of the method of manufacturing; and
(B) involving senior managers and experienced staff of the Food and Drug Administration, as appropriate, in a collaborative, cross-disciplinary review of the method of manufacturing, as applicable.
(2) Evaluation and designation
(d) Review of advanced manufacturing technologiesIf the Secretary designates a method of manufacturing as an advanced manufacturing technology, the Secretary shall—
(1) expedite the development and review of an application submitted under section 355 of this title or section 262 of title 42, including supplemental applications, for drugs that are manufactured using a designated advanced manufacturing technology; and
(2) allow the holder of an advanced technology designation, or a person authorized by the advanced manufacturing technology designation holder, to reference or rely upon, in an application submitted under section 355 of this title or section 262 of title 42, including a supplemental application, data and information about the designated advanced manufacturing technology for use in manufacturing drugs in the same context of use for which the designation was granted.
(e) Implementation and evaluation of advanced manufacturing technologies program
(1) Public meetingThe Secretary shall publish in the Federal Register a notice of a public meeting, to be held not later than 180 days after December 29, 2022, to discuss, and obtain input and recommendations from relevant stakeholders regarding—
(A) the goals and scope of the program under this section, and the framework, procedures, and requirements suitable for such program; and
(B) ways in which the Food and Drug Administration will support the use of advanced manufacturing technologies and other innovative manufacturing approaches for drugs.
(2) Program guidance
(A) In generalThe Secretary shall—
(i) not later than 180 days after the public meeting under paragraph (1), issue draft guidance regarding the goals and implementation of the program under this section; and
(ii) not later than 2 years after
(B) ContentThe guidance described in subparagraph (A) shall address—
(i) the process by which a person may request a designation under subsection (b);
(ii) the data and information that a person requesting such a designation is required to submit under subsection (c), and how the Secretary intends to evaluate such submissions;
(iii) the process to expedite the development and review of applications under subsection (d); and
(iv) the criteria described in subsection (b) for eligibility for such a designation.
(3) ReportNot later than 3 years after December 29, 2022, and annually thereafter, the Secretary shall publish on the website of the Food and Drug Administration and submit to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives a report containing a description and evaluation of the program being conducted under this section, including the types of innovative manufacturing approaches supported under the program. Such report shall include the following:
(A) The number of persons that have requested designations and that have been granted designations.
(B) The number of methods of manufacturing that have been the subject of designation requests and that have been granted designations.
(C) The average number of calendar days for completion of evaluations under subsection (c)(2).
(D) An analysis of the factors in data submissions that result in determinations to designate and not to designate after evaluation under subsection (c)(2).
(E) The number of applications received under section 355 of this title or section 262 of title 42, including supplemental applications, that have included an advanced manufacturing technology designated under this section, and the number of such applications approved.
(f) SunsetThe Secretary—
(1) may not consider any requests for designation submitted under subsection (c) after October 1, 2032; and
(2) may continue all activities under this section with respect to advanced manufacturing technologies that were designated pursuant to subsection (b) prior to such date, if the Secretary determines such activities are in the interest of the public health.
(June 25, 1938, ch. 675, § 506L, as added Pub. L. 117–328, div. FF, title III, § 3213, Dec. 29, 2022, 136 Stat. 5826.)

CITE AS: 21 USC 356l

§ 357. Qualification of drug development tools
(a) Process for qualification
(1) In generalThe Secretary shall establish a process for the qualification of drug development tools for a proposed context of use under which—
(A)
(i) a requestor initiates such process by submitting a letter of intent to the Secretary; and
(ii) the Secretary accepts or declines to accept such letter of intent;
(B)
(i) if the Secretary accepts the letter of intent, a requestor submits a qualification plan to the Secretary; and
(ii) the Secretary accepts or declines to accept the qualification plan; and
(C)
(i) if the Secretary accepts the qualification plan, the requestor submits to the Secretary a full qualification package;
(ii) the Secretary determines whether to accept such qualification package for review; and
(iii) if the Secretary accepts such qualification package for review, the Secretary conducts such review in accordance with this section.
(2) Acceptance and review of submissions
(A) In general
(B) Acceptance factors; nonacceptance
(C) Prioritization of qualification reviewThe Secretary may prioritize the review of a full qualification package submitted under paragraph (1) with respect to a drug development tool, based on factors determined appropriate by the Secretary, including—
(i) as applicable, the severity, rarity, or prevalence of the disease or condition targeted by the drug development tool and the availability or lack of alternative treatments for such disease or condition; and
(ii) the identification, by the Secretary or by biomedical research consortia and other expert stakeholders, of such a drug development tool and its proposed context of use as a public health priority.
(D) Engagement of external experts
(3) Review of full qualification packageThe Secretary shall—
(A) conduct a comprehensive review of a full qualification package accepted under paragraph (1)(C); and
(B) determine whether the drug development tool at issue is qualified for its proposed context of use.
(4) Qualification
(b) Effect of qualification
(1) In general
(2) Use of a drug development toolSubject to paragraph (3), a drug development tool qualified under this section may be used for—
(A) supporting or obtaining approval or licensure (as applicable) of a drug or biological product (including in accordance with section 356(c) of this title) under section 355 of this title or section 351 of the Public Health Service Act [42 U.S.C. 262]; or
(B) supporting the investigational use of a drug or biological product under section 355(i) of this title or section 351(a)(3) of the Public Health Service Act [42 U.S.C. 262(a)(3)].
(3) Rescission or modification
(A) In general
(B) Meeting for review
(c) Transparency
(1) In generalSubject to paragraph (3), the Secretary shall make publicly available, and update on at least a biannual basis, on the Internet website of the Food and Drug Administration the following:
(A) Information with respect to each qualification submission under the qualification process under subsection (a), including—
(i) the stage of the review process applicable to the submission;
(ii) the date of the most recent change in stage status;
(iii) whether external scientific experts were utilized in the development of a qualification plan or the review of a full qualification package; and
(iv) submissions from requestors under the qualification process under subsection (a), including any data and evidence contained in such submissions, and any updates to such submissions.
(B) The Secretary’s formal written determinations in response to such qualification submissions.
(C) Any rescissions or modifications under subsection (b)(3) of a determination to qualify a drug development tool.
(D) Summary reviews that document conclusions and recommendations for determinations to qualify drug development tools under subsection (a).
(E) A comprehensive list of—
(i) all drug development tools qualified under subsection (a); and
(ii) all surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or biological product (including in accordance with section 356(c) of this title) under section 355 of this title or section 351 of the Public Health Service Act [42 U.S.C. 262].
(2) Relation to Trade Secrets Act
(3) Applicability
(A) In generalNothing in this section shall be construed as authorizing or directing the Secretary to disclose—
(i) any information contained in an application submitted under section 355 of this title or section 351 of the Public Health Service Act [42 U.S.C. 262] that is confidential commercial or trade secret information subject to section 552(b)(4) of title 5 or section 1905 of title 18; or
(ii) in the case of a drug development tool that may be used to support the development of a qualified countermeasure, security countermeasure, or qualified pandemic or epidemic product, as defined in sections 319F–1, 319F–2, and 319F–3, respectively, of the Public Health Service Act [42 U.S.C. 247d–6a, 247d–6b, 247d–6d], any information that the Secretary determines has a significant potential to affect national security.
(B) Public acknowledgment
(d) Rule of constructionNothing in this section shall be construed—
(1) to alter the standards of evidence under subsection (c) or (d) of section 355 of this title, including the substantial evidence standard in such subsection (d), or under section 351 of the Public Health Service Act [42 U.S.C. 262] (as applicable); or
(2) to limit the authority of the Secretary to approve or license products under this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.], as applicable (as in effect before December 13, 2016).
(e) DefinitionsIn this section:
(1) BiomarkerThe term “biomarker”—
(A) means a characteristic (such as a physiologic, pathologic, or anatomic characteristic or measurement) that is objectively measured and evaluated as an indicator of normal biologic processes, pathologic processes, or biological responses to a therapeutic intervention; and
(B) includes a surrogate endpoint.
(2) Biomedical research consortia
(3) Clinical outcome assessmentThe term “clinical outcome assessment” means—
(A) a measurement of a patient’s symptoms, overall mental state, or the effects of a disease or condition on how the patient functions; and
(B) includes a patient-reported outcome.
(4) Context of use
(5) Drug development toolThe term “drug development tool” includes—
(A) a biomarker;
(B) a clinical outcome assessment; and
(C) any other method, material, or measure that the Secretary determines aids drug development and regulatory review for purposes of this section.
(6) Patient-reported outcome
(7) Qualification
(8) Requestor
(9) Surrogate endpoint
(A) is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or
(B) is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product in accordance with section 356(c) of this title.
(June 25, 1938, ch. 675, § 507, as added Pub. L. 114–255, div. A, title III, § 3011(a), Dec. 13, 2016, 130 Stat. 1086; amended Pub. L. 116–22, title VII, § 705(e), June 24, 2019, 133 Stat. 964.)

CITE AS: 21 USC 357

§ 358. Authority to designate official names
(a) Necessity or desirability; use in official compendiums; infringement of trademarks
(b) Review of names in official compendiums
(c) Determinations of complexity, usefulness, multiplicity, or lack of name; designation by Secretary
(d) Revised official names; compilation, publication, and public distribution of listings
(e) Request by compiler of official compendium for designation of name
(June 25, 1938, ch. 675, § 508, as added Pub. L. 87–781, title I, § 111(a), Oct. 10, 1962, 76 Stat. 789; amended Pub. L. 94–295, § 5(b), May 28, 1976, 90 Stat. 581; Pub. L. 103–80, § 3(q), Aug. 13, 1993, 107 Stat. 777.)

CITE AS: 21 USC 358

§ 359. Nonapplicability of subchapter to cosmetics

This subchapter, as amended by the Drug Amendments of 1962, shall not apply to any cosmetic unless such cosmetic is also a drug or device or component thereof.

(June 25, 1938, ch. 675, § 509, as added Pub. L. 87–781, title I, § 113, Oct. 10, 1962, 76 Stat. 791.)

CITE AS: 21 USC 359

§ 360. Registration of producers of drugs or devices
(a) DefinitionsAs used in this section—
(1) the term “manufacture, preparation, propagation, compounding, or processing” shall include repackaging or otherwise changing the container, wrapper, or labeling of any drug package or device package in furtherance of the distribution of the drug or device from the original place of manufacture to the person who makes final delivery or sale to the ultimate consumer or user; and
(2) the term “name” shall include in the case of a partnership the name of each partner and, in the case of a corporation, the name of each corporate officer and director, and the State of incorporation.
(b) Annual registration
(1) During the period beginning on October 1 and ending on December 31 of each year, every person who owns or operates any establishment in any State engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs shall register with the Secretary the name of such person, places of business of such person, all such establishments, the unique facility identifier of each such establishment, and a point of contact e-mail address.
(2) During the period beginning on October 1 and ending on December 31 of each year, every person who owns or operates any establishment in any State engaged in the manufacture, preparation, propagation, compounding, or processing of a device or devices shall register with the Secretary his name, places of business, and all such establishments.
(3) The Secretary shall specify the unique facility identifier system that shall be used by registrants under paragraph (1). The requirement to include a unique facility identifier in a registration under paragraph (1) shall not apply until the date that the identifier system is specified by the Secretary under the preceding sentence.
(c) New producersEvery person upon first engaging in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs or a device or devices in any establishment which he owns or operates in any State shall immediately register with the Secretary—
(1) with respect to drugs, the information described under subsection (b)(1); and
(2) with respect to devices, the information described under subsection (b)(2)..1
1 So in original.
(d) Additional establishments
(e) Registration number; uniform system for identification of devices intended for human use
(f) Availability of registrations for inspection
(g) Exclusions from application of sectionThe foregoing subsections of this section shall not apply to—
(1) pharmacies which maintain establishments in conformance with any applicable local laws regulating the practice of pharmacy and medicine and which are regularly engaged in dispensing prescription drugs or devices, upon prescriptions of practitioners licensed to administer such drugs or devices to patients under the care of such practitioners in the course of their professional practice, and which do not manufacture, prepare, propagate, compound, or process drugs or devices for sale other than in the regular course of their business of dispensing or selling drugs or devices at retail;
(2) practitioners licensed by law to prescribe or administer drugs or devices and who manufacture, prepare, propagate, compound, or process drugs or devices solely for use in the course of their professional practice;
(3) persons who manufacture, prepare, propagate, compound, or process drugs or devices solely for use in research, teaching, or chemical analysis and not for sale;
(4) any distributor who acts as a wholesale distributor of devices, and who does not manufacture, repackage, process, or relabel a device; or
(5) such other classes of persons as the Secretary may by regulation exempt from the application of this section upon a finding that registration by such classes of persons in accordance with this section is not necessary for the protection of the public health.
In this subsection, the term “wholesale distributor” means any person (other than the manufacturer or the initial importer) who distributes a device from the original place of manufacture to the person who makes the final delivery or sale of the device to the ultimate consumer or user.
(h) Inspections
(1) In general
(2) Risk-based schedule for devices
(A) In general
(B) Factors and considerationsIn establishing the risk-based schedule under subparagraph (A), the Secretary shall—
(i) apply, to the extent applicable for device establishments, the factors identified in paragraph (4); and
(ii) consider the participation of the device establishment, as applicable, in international device audit programs in which the United States participates or the United States recognizes for purposes of inspecting device establishments.
(3) Risk-based schedule for drugs
(4) Risk factorsIn establishing a risk-based schedule under paragraph (2) or (3), the Secretary shall inspect establishments according to the known safety risks of such establishments, which shall be based on the following factors:
(A) The compliance history of the establishment.
(B) The record, history, and nature of recalls linked to the establishment.
(C) The inherent risk of the drug or device manufactured, prepared, propagated, compounded, or processed at the establishment.
(D) The inspection frequency and history of the establishment, including whether the establishment has been inspected pursuant to section 374 of this title within the last 4 years.
(E) Whether the establishment has been inspected by a foreign government or an agency of a foreign government recognized under section 384e of this title.
(F) The compliance history of establishments in the country or region in which the establishment is located that are subject to regulation under this chapter, including the history of violations related to products exported from such country or region that are subject to such regulation.
(G) Any other criteria deemed necessary and appropriate by the Secretary for purposes of allocating inspection resources.
(5) Effect of status
(6) Annual report on inspections of establishmentsNot later than May 1 of each year, the Secretary shall make available on the Internet Web site of the Food and Drug Administration a report regarding—
(A)
(i) the number of domestic and foreign establishments registered pursuant to this section in the previous fiscal year;
(ii) the number of such registered establishments in each region of interest;
(iii) the number of such domestic establishments and the number of such foreign establishments, including the number of establishments in each region of interest, that the Secretary inspected in the previous fiscal year;
(iv) the number of inspections to support actions by the Secretary on applications under section 355 of this title or section 262 of title 42, including the number of inspections to support actions by the Secretary on supplemental applications, including changes to manufacturing processes, the Secretary conducted in the previous fiscal year;
(v) the number of routine surveillance inspections the Secretary conducted in the previous fiscal year, including in each region of interest;
(vi) the number of for-cause inspections the Secretary conducted in the previous fiscal year, not including inspections described in clause (iv), including in each region of interest; and
(vii) the number of inspections the Secretary has recognized pursuant to an agreement entered into pursuant to section 384e of this title, or otherwise recognized, for each of the types of inspections described in clauses (v) and (vi), including for inspections of establishments in each region of interest.2
2 So in original. The period probably should be a semicolon.
(B) with respect to establishments that manufacture, prepare, propagate, compound, or process an active ingredient of a drug or a finished drug product, the number of each such type of establishment;
(C) the percentage of the budget of the Food and Drug Administration used to fund the inspections described under subparagraph (A); and
(D) the status of the efforts of the Food and Drug Administration to expand its recognition of inspections conducted or recognized by foreign regulatory authorities under section 384e of this title, including any obstacles to expanding the use of such recognition.
(7) Region of interest
(i) Registration of foreign establishments
(1) Every person who owns or operates any establishment within any foreign country engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or device that is imported or offered for import into the United States shall, through electronic means in accordance with the criteria of the Secretary—
(A) upon first engaging in any such activity, immediately submit a registration to the Secretary that includes—
(i) with respect to drugs, the name and place of business of such person, all such establishments, the unique facility identifier of each such establishment, a point of contact e-mail address, the name of the United States agent of each such establishment, the name of each importer of such drug in the United States that is known to the establishment, and the name of each person who imports or offers for import such drug to the United States for purposes of importation; and
(ii) with respect to devices, the name and place of business of the establishment, the name of the United States agent for the establishment, the name of each importer of such device in the United States that is known to the establishment, and the name of each person who imports or offers for import such device to the United States for purposes of importation; and
(B) each establishment subject to the requirements of subparagraph (A) shall thereafter register with the Secretary during the period beginning on October 1 and ending on December 31 of each year.
(2) The establishment shall also provide the information required by subsection (j).
(3) The Secretary is authorized to enter into cooperative arrangements with officials of foreign countries to ensure that adequate and effective means are available for purposes of determining, from time to time, whether drugs or devices manufactured, prepared, propagated, compounded, or processed by an establishment described in paragraph (1), if imported or offered for import into the United States, shall be refused admission on any of the grounds set forth in section 381(a) of this title.
(4) The Secretary shall specify the unique facility identifier system that shall be used by registrants under paragraph (1) with respect to drugs. The requirement to include a unique facility identifier in a registration under paragraph (1) with respect to drugs shall not apply until the date that the identifier system is specified by the Secretary under the preceding sentence.
(5) The requirements of paragraphs (1) and (2) shall apply regardless of whether the drug or device undergoes further manufacture, preparation, propagation, compounding, or processing at a separate establishment outside the United States prior to being imported or offered for import into the United States.
(j) Filing of lists of drugs and devices manufactured, prepared, propagated and compounded by registrants; statements; accompanying disclosures
(1) Every person who registers with the Secretary under subsection (b), (c), (d), or (i) shall, at the time of registration under any such subsection, file with the Secretary a list of all drugs and a list of all devices and a brief statement of the basis for believing that each device included in the list is a device rather than a drug (with each drug and device in each list listed by its established name (as defined in section 352(e) of this title) and by any proprietary name) which are being manufactured, prepared, propagated, compounded, or processed by him for commercial distribution and which he has not included in any list of drugs or devices filed by him with the Secretary under this paragraph or paragraph (2) before such time of registration. Such list shall be prepared in such form and manner as the Secretary may prescribe and shall be accompanied by—
(A) in the case of a drug contained in the applicable list and subject to section 355 or 360b of this title, or a device intended for human use contained in the applicable list with respect to which a performance standard has been established under section 360d of this title or which is subject to section 360e of this title, a reference to the authority for the marketing of such drug or device and a copy of all labeling for such drug or device;
(B) in the case of any other drug or device contained in an applicable list—
(i) which drug is subject to section 353(b)(1) of this title, or which device is a restricted device, a copy of all labeling for such drug or device, a representative sampling of advertisements for such drug or device, and, upon request made by the Secretary for good cause, a copy of all advertisements for a particular drug product or device, or
(ii) which drug is not subject to section 353(b)(1) of this title or which device is not a restricted device, the label and package insert for such drug or device and a representative sampling of any other labeling for such drug or device;
(C) in the case of any drug contained in an applicable list which is described in subparagraph (B), a quantitative listing of its active ingredient or ingredients, except that with respect to a particular drug product the Secretary may require the submission of a quantitative listing of all ingredients if he finds that such submission is necessary to carry out the purposes of this chapter;
(D) if the registrant filing a list has determined that a particular drug product or device contained in such list is not subject to section 355 or 360b of this title, or the particular device contained in such list is not subject to a performance standard established under section 360d of this title or to section 360e of this title or is not a restricted device a brief statement of the basis upon which the registrant made such determination if the Secretary requests such a statement with respect to that particular drug product or device; and
(E) in the case of a drug contained in the applicable list, the name and place of business of each manufacturer of an excipient of the listed drug with which the person listing the drug conducts business, including all establishments used in the production of such excipient, the unique facility identifier of each such establishment, and a point of contact e-mail address for each such excipient manufacturer.
(2) Each person who registers with the Secretary under this section shall report to the Secretary, with regard to drugs once during the month of June of each year and once during the month of December of each year, and with regard to devices once each year during the period beginning on October 1 and ending on December 31, the following information:
(A) A list of each drug or device introduced by the registrant for commercial distribution which has not been included in any list previously filed by him with the Secretary under this subparagraph or paragraph (1) of this subsection. A list under this subparagraph shall list a drug or device by its established name (as defined in section 352(e) of this title), and by any proprietary name it may have and shall be accompanied by the other information required by paragraph (1).
(B) If since the date the registrant last made a report under this paragraph (or if he has not made a report under this paragraph, since February 1, 1973) he has discontinued the manufacture, preparation, propagation, compounding, or processing for commercial distribution of a drug or device included in a list filed by him under subparagraph (A) or paragraph (1); notice of such discontinuance, the date of such discontinuance, and the identity (by established name (as defined in section 352(e) of this title) and by any proprietary name) of such drug or device.
(C) If since the date the registrant reported pursuant to subparagraph (B) a notice of discontinuance he has resumed the manufacture, preparation, propagation, compounding, or processing for commercial distribution of the drug or device with respect to which such notice of discontinuance was reported; notice of such resumption, the date of such resumption, the identity of such drug or device (each by established name (as defined in section 352(e) of this title) and by any proprietary name), and the other information required by paragraph (1), unless the registrant has previously reported such resumption to the Secretary pursuant to this subparagraph.
(D) Any material change in any information previously submitted pursuant to this paragraph or paragraph (1).
(3)
(A) Each person who registers with the Secretary under this section with regard to a drug shall report annually to the Secretary on the amount of each drug listed under paragraph (1) that was manufactured, prepared, propagated, compounded, or processed by such person for commercial distribution. Such information may be required to be submitted in an electronic format as determined by the Secretary. The Secretary may require that information required to be reported under this paragraph be submitted at the time a public health emergency is declared by the Secretary under section 247d of title 42.
(B) By order of the Secretary, certain biological products or categories of biological products regulated under section 262 of title 42 may be exempt from some or all of the reporting requirements under subparagraph (A), if the Secretary determines that applying such reporting requirements to such biological products or categories of biological products is not necessary to protect the public health.
(4) The Secretary may also require each registrant under this section to submit a list of each drug product which (A) the registrant is manufacturing, preparing, propagating, compounding, or processing for commercial distribution, and (B) contains a particular ingredient. The Secretary may not require the submission of such a list unless he has made a finding that the submission of such a list is necessary to carry out the purposes of this chapter.
(5) The Secretary shall require persons subject to this subsection to use, for purposes of this subsection, the unique facility identifier systems specified under subsections (b)(3) and (i)(4) with respect to drugs. Such requirement shall not apply until the date that the identifier system under subsection (b)(3) or (i)(4), as applicable, is specified by the Secretary.
(k) Report preceding introduction of devices into interstate commerceEach person who is required to register under this section and who proposes to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of a device intended for human use shall, at least ninety days before making such introduction or delivery, report to the Secretary or person who is accredited under section 360m(a) of this title (in such form and manner as the Secretary shall by regulation prescribe)—
(1) the class in which the device is classified under section 360c of this title or if such person determines that the device is not classified under such section, a statement of that determination and the basis for such person’s determination that the device is or is not so classified, and
(2) action taken by such person to comply with requirements under section 360d or 360e of this title which are applicable to the device.
A notification submitted under this subsection that contains clinical trial data for an applicable device clinical trial (as defined in section 282(j)(1) of title 42) shall be accompanied by the certification required under section 282(j)(5)(B) of such title. Such certification shall not be considered an element of such notification.
(l) Exemption from reporting requirements
(1) A report under subsection (k) is not required for a device intended for human use that is exempted from the requirements of this subsection under subsection (m) or is within a type that has been classified into class I under section 360c of this title, or with respect to a change that is consistent with a predetermined change control plan cleared under section 360e–4 of this title. The exception established in the preceding sentence does not apply to any class I device that is intended for a use which is of substantial importance in preventing impairment of human health, or to any class I device that presents a potential unreasonable risk of illness or injury.
(2) Not later than 120 calendar days after December 13, 2016, and at least once every 5 years thereafter, as the Secretary determines appropriate, the Secretary shall identify, through publication in the Federal Register, any type of class I device that the Secretary determines no longer requires a report under subsection (k) to provide reasonable assurance of safety and effectiveness. Upon such publication—
(A) each type of class I device so identified shall be exempt from the requirement for a report under subsection (k); and
(B) the classification regulation applicable to each such type of device shall be deemed amended to incorporate such exemption.
(m) List of exempt class II devices; initial and final determinations by Secretary; publication in Federal Register
(1) The Secretary shall—
(A) not later than 90 days after December 13, 2016, and at least once every 5 years thereafter, as the Secretary determines appropriate—
(i) publish in the Federal Register a notice that contains a list of each type of class II device that the Secretary determines no longer requires a report under subsection (k) to provide reasonable assurance of safety and effectiveness; and
(ii) provide for a period of not less than 60 calendar days for public comment beginning on the date of the publication of such notice; and
(B) not later than 210 calendar days after December 13, 2016, publish in the Federal Register a list representing the Secretary’s final determination with respect to the devices contained in the list published under subparagraph (A).
(2) Beginning on the date that is 1 calendar day after the date of publication of the final list under paragraph (1)(B), the Secretary may exempt a class II device from the requirement to submit a report under subsection (k), upon the Secretary’s own initiative or a petition of an interested person, if the Secretary determines that such report is not necessary to assure the safety and effectiveness of the device. The Secretary shall publish in the Federal Register notice of the intent of the Secretary to exempt the device, or of the petition, and provide a 60-calendar-day period for public comment. Within 120 days after the issuance of the notice in the Federal Register, the Secretary shall publish an order in the Federal Register that sets forth the final determination of the Secretary regarding the exemption of the device that was the subject of the notice. If the Secretary fails to respond to a petition within 180 days of receiving it, the petition shall be deemed to be granted.
(3) Upon the publication of the final list under paragraph (1)(B)—
(A) each type of class II device so listed shall be exempt from the requirement for a report under subsection (k); and
(B) the classification regulation applicable to each such type of device shall be deemed amended to incorporate such exemption.
(n) Review of report; time for determination by Secretary
(1) The Secretary shall review the report required in subsection (k) and make a determination under section 360c(f)(1) of this title not later than 90 days after receiving the report.
(2)
(A) Not later than 18 months after July 9, 2012, the Secretary shall submit to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate a report regarding when a premarket notification under subsection (k) should be submitted for a modification or change to a legally marketed device. The report shall include the Secretary’s interpretation of the following terms: “could significantly affect the safety or effectiveness of the device”, “a significant change or modification in design, material, chemical composition, energy source, or manufacturing process”, and “major change or modification in the intended use of the device”. The report also shall discuss possible processes for industry to use to determine whether a new submission under subsection (k) is required and shall analyze how to leverage existing quality system requirements to reduce premarket burden, facilitate continual device improvement, and provide reasonable assurance of safety and effectiveness of modified devices. In developing such report, the Secretary shall consider the input of interested stakeholders.
(B) The Secretary shall withdraw the Food and Drug Administration draft guidance entitled “Guidance for Industry and FDA Staff—510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device”, dated July 27, 2011, and shall not use this draft guidance as part of, or for the basis of, any premarket review or any compliance or enforcement decisions or actions. The Secretary shall not issue—
(i) any draft guidance or proposed regulation that addresses when to submit a premarket notification submission for changes and modifications made to a manufacturer’s previously cleared device before the receipt by the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate of the report required in subparagraph (A); and
(ii) any final guidance or regulation on that topic for one year after date of receipt of such report by the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate.
(C) The Food and Drug Administration guidance entitled “Deciding When to Submit a 510(k) for a Change to an Existing Device”, dated January 10, 1997, shall be in effect until the subsequent issuance of guidance or promulgation, if appropriate, of a regulation described in subparagraph (B), and the Secretary shall interpret such guidance in a manner that is consistent with the manner in which the Secretary has interpreted such guidance since 1997.
(o) Reprocessed single-use devices
(1) With respect to reprocessed single-use devices for which reports are required under subsection (k):
(A) The Secretary shall identify such devices or types of devices for which reports under such subsection must, in order to ensure that the device is substantially equivalent to a predicate device, include validation data, the types of which shall be specified by the Secretary, regarding cleaning and sterilization, and functional performance demonstrating that the single-use device will remain substantially equivalent to its predicate device after the maximum number of times the device is reprocessed as intended by the person submitting the premarket notification. Within six months after October 26, 2002, the Secretary shall publish in the Federal Register a list of the types so identified, and shall revise the list as appropriate. Reports under subsection (k) for devices or types of devices within a type included on the list are, upon publication of the list, required to include such validation data.
(B) In the case of each report under subsection (k) that was submitted to the Secretary before the publication of the initial list under subparagraph (A), or any revision thereof, and was for a device or type of device included on such list, the person who submitted the report under subsection (k) shall submit validation data as described in subparagraph (A) to the Secretary not later than nine months after the publication of the list. During such nine-month period, the Secretary may not take any action under this chapter against such device solely on the basis that the validation data for the device have not been submitted to the Secretary. After the submission of the validation data to the Secretary, the Secretary may not determine that the device is misbranded under section 352(o) of this title or adulterated under section 351(f)(1)(B) of this title, or take action against the device under section 331(p) of this title for failure to provide any information required by subsection (k) until (i) the review is terminated by withdrawal of the submission of the report under subsection (k); (ii) the Secretary finds the data to be acceptable and issues a letter; or (iii) the Secretary determines that the device is not substantially equivalent to a predicate device. Upon a determination that a device is not substantially equivalent to a predicate device, or if such submission is withdrawn, the device can no longer be legally marketed.
(C) In the case of a report under subsection (k) for a device identified under subparagraph (A) that is of a type for which the Secretary has not previously received a report under such subsection, the Secretary may, in advance of revising the list under subparagraph (A) to include such type, require that the report include the validation data specified in subparagraph (A).
(D) Section 352(o) of this title applies with respect to the failure of a report under subsection (k) to include validation data required under subparagraph (A).
(2) With respect to critical or semi-critical reprocessed single-use devices that, under subsection (l) or (m), are exempt from the requirement of submitting reports under subsection (k):
(A) The Secretary shall identify such devices or types of devices for which such exemptions should be terminated in order to provide a reasonable assurance of the safety and effectiveness of the devices. The Secretary shall publish in the Federal Register a list of the devices or types of devices so identified, and shall revise the list as appropriate. The exemption for each device or type included on the list is terminated upon the publication of the list. For each report under subsection (k) submitted pursuant to this subparagraph the Secretary shall require the validation data described in paragraph (1)(A).
(B) For each device or type of device included on the list under subparagraph (A), a report under subsection (k) shall be submitted to the Secretary not later than 15 months after the publication of the initial list, or a revision of the list, whichever terminates the exemption for the device. During such 15-month period, the Secretary may not take any action under this chapter against such device solely on the basis that such report has not been submitted to the Secretary. After the submission of the report to the Secretary the Secretary may not determine that the device is misbranded under section 352(o) of this title or adulterated under section 351(f)(1)(B) of this title, or take action against the device under section 331(p) of this title for failure to provide any information required by subsection (k) until (i) the review is terminated by withdrawal of the submission; (ii) the Secretary determines by order that the device is substantially equivalent to a predicate device; or (iii) the Secretary determines by order that the device is not substantially equivalent to a predicate device. Upon a determination that a device is not substantially equivalent to a predicate device, the device can no longer be legally marketed.
(C) In the case of semi-critical devices, the initial list under subparagraph (A) shall be published not later than 18 months after the effective date of this subsection. In the case of critical devices, the initial list under such subparagraph shall be published not later than six months after such effective date.
(D) Section 352(o) of this title applies with respect to the failure to submit a report under subsection (k) that is required pursuant to subparagraph (A), including a failure of the report to include validation data required in such subparagraph.
(E) The termination under subparagraph (A) of an exemption under subsection (l) or (m) for a critical or semi-critical reprocessed single-use device does not terminate the exemption under subsection (l) or (m) for the original device.
(p) Electronic registration and listing
(1) In general
(2) Electronic databaseNot later than 2 years after the Secretary specifies a unique facility identifier system under subsections (b) and (i), the Secretary shall maintain an electronic database, which shall not be subject to inspection under subsection (f), populated with the information submitted as described under paragraph (1) that—
(A) enables personnel of the Food and Drug Administration to search the database by any field of information submitted in a registration described under paragraph (1), or combination of such fields; and
(B) uses the unique facility identifier system to link with other relevant databases within the Food and Drug Administration, including the database for submission of information under section 381(r) of this title.
(3) Risk-based information and coordination
(q) Reusable medical devices
(1) In generalNot later than 180 days after December 13, 2016, the Secretary shall identify and publish a list of reusable device types for which reports under subsection (k) are required to include—
(A) instructions for use, which have been validated in a manner specified by the Secretary; and
(B) validation data, the types of which shall be specified by the Secretary;
regarding cleaning, disinfection, and sterilization, and for which a substantial equivalence determination may be based.
(2) Revision of list
(3) Content of reports
(June 25, 1938, ch. 675, § 510, as added Pub. L. 87–781, title III, § 302, Oct. 10, 1962, 76 Stat. 794; amended Pub. L. 89–74, § 4, July 15, 1965, 79 Stat. 231; Pub. L. 91–513, title II, § 701(e), Oct. 27, 1970, 84 Stat. 1282; Pub. L. 92–387, §§ 3, 4(a)–(c), Aug. 16, 1972, 86 Stat. 560–562; Pub. L. 94–295, § 4(a), May 28, 1976, 90 Stat. 579; Pub. L. 105–115, title I, § 125(a)(2)(C), title II, §§ 206(a), 209(a), 213(b), title IV, § 417, Nov. 21, 1997, 111 Stat. 2325, 2338, 2341, 2347, 2379; Pub. L. 107–188, title III, § 321(a), June 12, 2002, 116 Stat. 675; Pub. L. 107–250, title II, §§ 201(e), 207, 211, title III, § 302(b), Oct. 26, 2002, 116 Stat. 1609, 1613, 1614, 1616; Pub. L. 108–214, § 2(c)(2), Apr. 1, 2004, 118 Stat. 576; Pub. L. 110–85, title II, §§ 222–224, title VIII, § 801(b)(3)(C), Sept. 27, 2007, 121 Stat. 853, 921; Pub. L. 112–144, title VI, § 604, title VII, §§ 701, 702(b)–705, July 9, 2012, 126 Stat. 1052, 1064–1066; Pub. L. 114–255, div. A, title III, §§ 3054, 3059(a), 3101(a)(2)(H), Dec. 13, 2016, 130 Stat. 1126, 1130, 1154; Pub. L. 115–52, title VII, § 701(a), title IX, § 901(e), Aug. 18, 2017, 131 Stat. 1054, 1076; Pub. L. 116–136, div. A, title III, § 3112(e), Mar. 27, 2020, 134 Stat. 363; Pub. L. 117–328, div. FF, title II, §§ 2511(a), 2515(a)(3), title III, §§ 3308(b)(1), 3613(a), 3616(c), Dec. 29, 2022, 136 Stat. 5803, 5806, 5836, 5872, 5875.)

CITE AS: 21 USC 360

§ 360a. Clinical trial guidance for antibiotic drugs
(a) In general
(b) Review
(June 25, 1938, ch. 675, § 511, as added Pub. L. 110–85, title IX, § 911, Sept. 27, 2007, 121 Stat. 951.)

CITE AS: 21 USC 360a

§ 360a–1. Clinical trials
(a) Review and revision of guidance documents
(1) In general
The Secretary of Health and Human Services (referred to in this section as the “Secretary”) shall review and, as appropriate, revise not fewer than 3 guidance documents per year, which shall include—
(A) reviewing the guidance documents of the Food and Drug Administration for the conduct of clinical trials with respect to antibacterial and antifungal drugs; and
(B) as appropriate, revising such guidance documents to reflect developments in scientific and medical information and technology and to ensure clarity regarding the procedures and requirements for approval of antibacterial and antifungal drugs under chapter V of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351 et seq.).
(2) Issues for review
(3) Rule of construction
(b) Recommendations for investigations
(1) Request
(2) Recommendations
(c) Qualified infectious disease product
(Pub. L. 112–144, title VIII, § 804, July 9, 2012, 126 Stat. 1080.)

CITE AS: 21 USC 360a-1

§ 360a–2. Susceptibility test interpretive criteria for microorganisms
(a) Purpose; identification of criteria
(1) PurposeThe purpose of this section is to clarify the Secretary’s authority to—
(A) efficiently update susceptibility test interpretive criteria for antimicrobial drugs when necessary for public health, due to, among other things, the constant evolution of microorganisms that leads to the development of resistance to drugs that have been effective in decreasing morbidity and mortality for patients, which warrants unique management of antimicrobial drugs that is inappropriate for most other drugs in order to delay or prevent the development of further resistance to existing therapies;
(B) provide for public notice of the availability of recognized interpretive criteria and interpretive criteria standards; and
(C) clear under section 360(k) of this title, classify under section 360c(f)(2) of this title, or approve under section 360e of this title, antimicrobial susceptibility testing devices utilizing updated, recognized susceptibility test interpretive criteria to characterize the in vitro susceptibility of particular bacteria, fungi, or other microorganisms, as applicable, to antimicrobial drugs.
(2) Identification of criteriaThe Secretary shall identify appropriate susceptibility test interpretive criteria with respect to antimicrobial drugs—
(A) if such criteria are available on the date of approval of the drug under section 355 of this title or licensure of the drug under section 262 of title 42 (as applicable), upon such approval or licensure; or
(B) if such criteria are unavailable on such date, on the date on which such criteria are available for such drug.
(3) Bases for initial identificationThe Secretary shall identify appropriate susceptibility test interpretive criteria under paragraph (2), based on the Secretary’s review of, to the extent available and relevant—
(A) preclinical and clinical data, including pharmacokinetic, pharmacodynamic, and epidemiological data;
(B) the relationship of susceptibility test interpretive criteria to morbidity and mortality associated with the disease or condition for which such drug is used; and
(C) such other evidence and information as the Secretary considers appropriate.
(b) Susceptibility test Interpretive Criteria Website
(1) In general
(2) Listing of susceptibility test interpretive criteria standards and interpretive criteria
(A) In generalThe list described in paragraph (1) shall consist of any new or updated susceptibility test interpretive criteria standards that are—
(i) established by a nationally or internationally recognized standard development organization that—(I) establishes and maintains procedures to address potential conflicts of interest and ensure transparent decisionmaking;(II) holds open meetings to ensure that there is an opportunity for public input by interested parties, and establishes and maintains processes to ensure that such input is considered in decisionmaking; and(III) permits its standards to be made publicly available, through the National Library of Medicine or another similar source acceptable to the Secretary; and
(ii) recognized in whole, or in part, by the Secretary under subsection (c).
(B) Other listThe Interpretive Criteria Website shall, in addition to the list described in subparagraph (A), include a list of interpretive criteria, if any, that the Secretary has determined to be appropriate with respect to legally marketed antimicrobial drugs, where—
(i) the Secretary does not recognize, in whole or in part, an interpretive criteria standard described under subparagraph (A) otherwise applicable to such a drug;
(ii) the Secretary withdraws under subsection (c)(1)(A) recognition of a standard, in whole or in part, otherwise applicable to such a drug;
(iii) the Secretary approves an application under section 355 of this title or section 262 of title 42, as applicable, with respect to marketing of such a drug for which there are no relevant interpretive criteria included in a standard recognized by the Secretary under subsection (c); or
(iv) because the characteristics of such a drug differ from other drugs with the same active ingredient, the interpretive criteria with respect to such drug—(I) differ from otherwise applicable interpretive criteria included in a standard listed under subparagraph (A) or interpretive criteria otherwise listed under this subparagraph; and(II) are determined by the Secretary to be appropriate for the drug.
(C) Required statementsThe Interpretive Criteria Website shall include statements conveying—
(i) that the website provides information about the in vitro susceptibility of bacteria, fungi, or other microorganisms, as applicable to a certain drug (or drugs);
(ii) that—(I) the safety and efficacy of such drugs in treating clinical infections due to such bacteria, fungi, or other microorganisms, as applicable, may or may not have been established in adequate and well-controlled clinical trials in order for the susceptibility information described in clause (i) to be included on the website; and(II) the clinical significance of such susceptibility information in such instances is unknown;
(iii) that the approved product labeling for specific drugs provides the uses for which the Secretary has approved the product; and
(iv) any other information that the Secretary determines appropriate to adequately convey the meaning of the data supporting the recognition or listing of susceptibility test interpretive criteria standards or susceptibility test interpretive criteria included on the website.
(3) Notice
(4) Inapplicability of misbranding provision
(5) Trade secrets and confidential information
(c) Recognition of susceptibility test interpretive criteria
(1) Evaluation and publication
(A) In generalBeginning on the date of the establishment of the Interpretive Criteria Website, and at least every 6 months thereafter, the Secretary shall—
(i) evaluate any appropriate new or updated susceptibility test interpretive criteria standards established by a nationally or internationally recognized standard development organization described in subsection (b)(2)(A)(i); and
(ii) publish on the public website of the Food and Drug Administration a notice—(I) withdrawing recognition of any different susceptibility test interpretive criteria standard, in whole or in part;(II) recognizing the new or updated standards;(III) recognizing one or more parts of the new or updated interpretive criteria specified in such a standard and declining to recognize the remainder of such standard; and(IV) making any necessary updates to the lists under subsection (b)(2).
(B) Upon approval of a drug
(2) Bases for updating interpretive criteria standardsIn evaluating new or updated susceptibility test interpretive criteria standards under paragraph (1)(A), the Secretary may consider—
(A) the Secretary’s determination that such a standard is not applicable to a particular drug because the characteristics of the drug differ from other drugs with the same active ingredient;
(B) information provided by interested third parties, including public comment on the annual compilation of notices published under paragraph (3);
(C) any bases used to identify susceptibility test interpretive criteria under subsection (a)(2); and
(D) such other information or factors as the Secretary determines appropriate.
(3) Annual compilation of noticesEach year, the Secretary shall compile the notices published under paragraph (1)(A) and publish such compilation in the Federal Register and provide for public comment. If the Secretary receives comments, the Secretary shall review such comments and, if the Secretary determines appropriate, update pursuant to this subsection susceptibility test interpretive criteria standards or criteria—
(A) recognized by the Secretary under this subsection; or
(B) otherwise listed on the Interpretive Criteria Website under subsection (b)(2).
(4) Relation to section 360d(c) of this title
(5) Voluntary use of interpretive criteria
(d) Antimicrobial drug labeling
(1) Drugs marketed prior to establishment of Interpretive Criteria Website
(A) In general
(B) Labeling changes
(2) Drugs marketed subsequent to establishment of Interpretive Criteria Website
(e) Special condition for marketing of antimicrobial susceptibility testing devices
(1) In general
(2) Conditions applicable to antimicrobial susceptibility testing devicesThe conditions specified in this paragraph are the following:
(A) The device is used to make a determination of susceptibility using susceptibility test interpretive criteria that are—
(i) included in a standard recognized by the Secretary under subsection (c); or
(ii) otherwise listed on the Interpretive Criteria Website under subsection (b)(2).
(B) The labeling of such device includes statements conveying—
(i) that the device provides information about the in vitro susceptibility of bacteria, fungi, or other microorganisms, as applicable to antimicrobial drugs;
(ii) that—(I) the safety and efficacy of such drugs in treating clinical infections due to such bacteria, fungi, or other microorganisms, as applicable, may or may not have been established in adequate and well-controlled clinical trials in order for the device to report the susceptibility of such bacteria, fungi, or other microorganisms, as applicable, to such drugs; and(II) the clinical significance of such susceptibility information in those instances is unknown;
(iii) that the approved labeling for drugs tested using such a device provides the uses for which the Secretary has approved such drugs; and
(iv) any other information the Secretary determines appropriate to adequately convey the meaning of the data supporting the recognition or listing of susceptibility test interpretive criteria standards or susceptibility test interpretive criteria described in subparagraph (A).
(C) The antimicrobial susceptibility testing device meets all other requirements to be cleared under section 360(k) of this title, classified under section 360c(f)(2) of this title, or approved under section 360e of this title.
(f) DefinitionsIn this section:
(1) The term “antimicrobial susceptibility testing device” means a device that utilizes susceptibility test interpretive criteria to determine and report the in vitro susceptibility of certain microorganisms to a drug (or drugs).
(2) The term “qualified infectious disease product” means a qualified infectious disease product designated under section 355f(d) of this title.
(3) The term “susceptibility test interpretive criteria” means—
(A) one or more specific numerical values which characterize the susceptibility of bacteria or other microorganisms to the drug tested; and
(B) related categorizations of such susceptibility, including categorization of the drug as susceptible, intermediate, resistant, or such other term as the Secretary determines appropriate.
(4)
(A) The term “antimicrobial drug” means, subject to subparagraph (B), a systemic antibacterial or antifungal drug that—
(i) is intended for human use in the treatment of a disease or condition caused by a bacterium or fungus;
(ii) may include a qualified infectious disease product designated under section 355f(d) of this title; and
(iii) is subject to section 353(b)(1) of this title.
(B) If provided by the Secretary through regulations, such term may include—
(i) drugs other than systemic antibacterial and antifungal drugs; and
(ii) biological products (as such term is defined in section 262 of title 42) to the extent such products exhibit antimicrobial activity.
(5) The term “interpretive criteria standard” means a compilation of susceptibility test interpretive criteria developed by a standard development organization that meets the criteria set forth in subsection (b)(2)(A)(i).
(g) Rule of constructionNothing in this section shall be construed to—
(1) alter the standards of evidence under subsection (c) or (d) of section 355 of this title (including the substantial evidence standard under section 355(d) of this title) or under section 262 of title 42 (as applicable); or
(2) with respect to clearing devices under section 360(k) of this title, classifying devices under section 360c(f)(2) of this title, or approving devices under section 360e of this title—
(A) apply with respect to any drug, device, or biological product, in any context other than an antimicrobial drug and an antimicrobial susceptibility testing device that uses susceptibility test interpretive criteria to characterize and report the susceptibility of certain bacteria, fungi, or other microorganisms, as applicable, to such drug to reflect patient morbidity and mortality in accordance with this section; or
(B) unless specifically stated, have any effect on authorities provided under other sections of this chapter, including any regulations issued under such sections.
(June 25, 1938, ch. 675, § 511A, as added Pub. L. 114–255, div. A, title III, § 3044(a), Dec. 13, 2016, 130 Stat. 1114.)

CITE AS: 21 USC 360a-2

§ 360b. New animal drugs
(a) Unsafe new animal drugs and animal feed containing such drugs; conditions of safety; exemption of drugs for research; import tolerances
(1) A new animal drug shall, with respect to any particular use or intended use of such drug, be deemed unsafe for purposes of section 351(a)(5) of this title and section 342(a)(2)(C)(ii) of this title unless—
(A) there is in effect an approval of an application filed pursuant to subsection (b) with respect to such use or intended use of such drug, and such drug, its labeling, and such use conform to such approved application;
(B) there is in effect a conditional approval of an application filed pursuant to section 360ccc of this title with respect to such use or intended use of such drug, and such drug, its labeling, and such use conform to such conditionally approved application;
(C) there is in effect an index listing pursuant to section 360ccc–1 of this title with respect to such use or intended use of such drug in a minor species, and such drug, its labeling, and such use conform to such index listing; or
(D) there is in effect an authorization pursuant to section 360bbb–3 of this title with respect to such use or intended use of such drug, and such drug, its labeling, and such use conform to any conditions of such authorization.
A new animal drug shall also be deemed unsafe for such purposes in the event of removal from the establishment of a manufacturer, packer, or distributor of such drug for use in the manufacture of animal feed in any State unless at the time of such removal such manufacturer, packer, or distributor has an unrevoked written statement from the consignee of such drug, or notice from the Secretary, to the effect that, with respect to the use of such drug in animal feed, such consignee (i) holds a license issued under subsection (m) and has in its possession current approved labeling for such drug in animal feed; or (ii) will, if the consignee is not a user of the drug, ship such drug only to a holder of a license issued under subsection (m).
(2) An animal feed bearing or containing a new animal drug shall, with respect to any particular use or intended use of such animal feed be deemed unsafe for purposes of section 351(a)(6) of this title unless—
(A) there is in effect—
(i) an approval of an application filed pursuant to subsection (b) with respect to such drug, as used in such animal feed, and such animal feed and its labeling, distribution, holding, and use conform to such approved application;
(ii) a conditional approval of an application filed pursuant to section 360ccc of this title with respect to such drug, as used in such animal feed, and such animal feed and its labeling, distribution, holding, and use conform to such conditionally approved application; or
(iii) an index listing pursuant to section 360ccc–1 of this title with respect to such drug, as used in such animal feed, and such animal feed and its labeling, distribution, holding, and use conform to such index listing; and
(B) such animal feed is manufactured at a site for which there is in effect a license issued pursuant to subsection (m)(1) to manufacture such animal feed.
(3) A new animal drug or an animal feed bearing or containing a new animal drug shall not be deemed unsafe for the purposes of section 351(a)(5) or (6) of this title if such article is for investigational use and conforms to the terms of an exemption in effect with respect thereto under subsection (j).
(4)
(A) Except as provided in subparagraph (B), if an approval of an application filed under subsection (b) is in effect with respect to a particular use or intended use of a new animal drug, the drug shall not be deemed unsafe for the purposes of paragraph (1) and shall be exempt from the requirements of section 352(f) of this title with respect to a different use or intended use of the drug, other than a use in or on animal feed, if such use or intended use—
(i) is by or on the lawful written or oral order of a licensed veterinarian within the context of a veterinarian-client-patient relationship, as defined by the Secretary; and
(ii) is in compliance with regulations promulgated by the Secretary that establish the conditions for such different use or intended use.
The regulations promulgated by the Secretary under clause (ii) may prohibit particular uses of an animal drug and shall not permit such different use of an animal drug if the labeling of another animal drug that contains the same active ingredient and which is in the same dosage form and concentration provides for such different use.
(B) If the Secretary finds that there is a reasonable probability that a use of an animal drug authorized under subparagraph (A) may present a risk to the public health, the Secretary may—
(i) establish a safe level for a residue of an animal drug when it is used for such different use authorized by subparagraph (A); and
(ii) require the development of a practical, analytical method for the detection of residues of such drug above the safe level established under clause (i).
The use of an animal drug that results in residues exceeding a safe level established under clause (i) shall be considered an unsafe use of such drug under paragraph (1). Safe levels may be established under clause (i) either by regulation or order.
(C) The Secretary may by general regulation provide access to the records of veterinarians to ascertain any use or intended use authorized under subparagraph (A) that the Secretary has determined may present a risk to the public health.
(D) If the Secretary finds, after affording an opportunity for public comment, that a use of an animal drug authorized under subparagraph (A) presents a risk to the public health or that an analytical method required under subparagraph (B) has not been developed and submitted to the Secretary, the Secretary may, by order, prohibit any such use.
(5) If the approval of an application filed under section 355 of this title is in effect, the drug under such application shall not be deemed unsafe for purposes of paragraph (1) and shall be exempt from the requirements of section 352(f) of this title with respect to a use or intended use of the drug in animals if such use or intended use—
(A) is by or on the lawful written or oral order of a licensed veterinarian within the context of a veterinarian-client-patient relationship, as defined by the Secretary; and
(B) is in compliance with regulations promulgated by the Secretary that establish the conditions for the use or intended use of the drug in animals.
(6) For purposes of section 342(a)(2)(D) 1
1 See References in Text note below.
of this title, a use or intended use of a new animal drug shall not be deemed unsafe under this section if the Secretary establishes a tolerance for such drug and any edible portion of any animal imported into the United States does not contain residues exceeding such tolerance. In establishing such tolerance, the Secretary shall rely on data sufficient to demonstrate that a proposed tolerance is safe based on similar food safety criteria used by the Secretary to establish tolerances for applications for new animal drugs filed under subsection (b)(1). The Secretary may consider and rely on data submitted by the drug manufacturer, including data submitted to appropriate regulatory authorities in any country where the new animal drug is lawfully used or data available from a relevant international organization, to the extent such data are not inconsistent with the criteria used by the Secretary to establish a tolerance for applications for new animal drugs filed under subsection (b)(1). For purposes of this paragraph, “relevant international organization” means the Codex Alimenterius 2
2 So in original. Probably should be “Alimentarius”.
Commission or other international organization deemed appropriate by the Secretary. The Secretary may, under procedures specified by regulation, revoke a tolerance established under this paragraph if information demonstrates that the use of the new animal drug under actual use conditions results in food being imported into the United States with residues exceeding the tolerance or if scientific evidence shows the tolerance to be unsafe.
(b) Filing application for uses of new animal drug; contents; patent information; abbreviated application; presubmission conference
(1) Any person may file with the Secretary an application with respect to any intended use or uses of a new animal drug. Such person shall submit to the Secretary as a part of the application (A) full reports of investigations which have been made to show whether or not such drug is safe and effective for use; (B) a full list of the articles used as components of such drug; (C) a full statement of the composition of such drug; (D) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug; (E) such samples of such drug and of the articles used as components thereof, of any animal feed for use in or on which such drug is intended, and of the edible portions or products (before or after slaughter) of animals to which such drug (directly or in or on animal feed) is intended to be administered, as the Secretary may require; (F) specimens of the labeling proposed to be used for such drug, or in case such drug is intended for use in animal feed, proposed labeling appropriate for such use, and specimens of the labeling for the drug to be manufactured, packed, or distributed by the applicant; (G) a description of practicable methods for determining the quantity, if any, of such drug in or on food, and any substance formed in or on food, because of its use; and (H) the proposed tolerance or withdrawal period or other use restrictions for such drug if any tolerance or withdrawal period or other use restrictions are required in order to assure that the proposed use of such drug will be safe. The applicant shall file with the application the patent number and the expiration date of any patent which claims the new animal drug for which the applicant filed the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If an application is filed under this subsection for a drug and a patent which claims such drug or a method of using such drug is issued after the filing date but before approval of the application, the applicant shall amend the application to include the information required by the preceding sentence. Upon approval of the application, the Secretary shall publish information submitted under the two preceding sentences.
(2) Any person may file with the Secretary an abbreviated application for the approval of a new animal drug. An abbreviated application shall contain the information required by subsection (n).
(3) Any person intending to file an application under paragraph (1), section 360ccc of this title, or a request for an investigational exemption under subsection (j) shall be entitled to one or more conferences prior to such submission to reach an agreement acceptable to the Secretary establishing a submission or an investigational requirement, which may include a requirement for a field investigation. A decision establishing a submission or an investigational requirement shall bind the Secretary and the applicant or requestor unless (A) the Secretary and the applicant or requestor mutually agree to modify the requirement, or (B) the Secretary by written order determines that a substantiated scientific requirement essential to the determination of safety or effectiveness of the animal drug involved has appeared after the conference. No later than 25 calendar days after each such conference, the Secretary shall provide a written order setting forth a scientific justification specific to the animal drug and intended uses under consideration if the agreement referred to in the first sentence requires more than one field investigation as being essential to provide substantial evidence of effectiveness for the intended uses of the drug. Nothing in this paragraph shall be construed as compelling the Secretary to require a field investigation.
(4) Beginning on October 1, 2018, all applications or submissions pursuant to this subsection shall be submitted by electronic means in such format as the Secretary may require.
(c) Period for submission and approval of application; period for notice and expedition of hearing; period for issuance of order; abbreviated applications; withdrawal periods; effective date of approval; relationship to other applications; withdrawal or suspension of approval; bioequivalence; filing of additional patent information
(1) Within one hundred and eighty days after the filing of an application pursuant to subsection (b), or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either (A) issue an order approving the application if he then finds that none of the grounds for denying approval specified in subsection (d) applies, or (B) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) on the question whether such application is approvable. If the applicant elects to accept the opportunity for a hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary’s order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(2)
(A) Subject to subparagraph (C), the Secretary shall approve an abbreviated application for a drug unless the Secretary finds—
(i) the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug are inadequate to assure and preserve its identity, strength, quality, and purity;
(ii) the conditions of use prescribed, recommended, or suggested in the proposed labeling are not reasonably certain to be followed in practice or, except as provided in subparagraph (B), information submitted with the application is insufficient to show that each of the proposed conditions of use or similar limitations (whether in the labeling or published pursuant to subsection (i)) have been previously approved for the approved new animal drug referred to in the application;
(iii) information submitted with the application is insufficient to show that the active ingredients are the same as those of the approved new animal drug referred to in the application;
(iv)(I) if the application is for a drug whose active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is the same as the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed of the approved new animal drug referred to in the application, information submitted in the application is insufficient to show that the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is the same as that of the approved new animal drug, or(II) if the application is for a drug whose active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is different from that of the approved new animal drug referred to in the application, no petition to file an application for the drug with the different active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed was approved under subsection (n)(3);
(v) if the application was filed pursuant to the approval of a petition under subsection (n)(3), the application did not contain the information required by the Secretary respecting the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed which is not the same;
(vi) information submitted in the application is insufficient to show that the drug is bioequivalent to the approved new animal drug referred to in the application, or if the application is filed under a petition approved pursuant to subsection (n)(3), information submitted in the application is insufficient to show that the active ingredients of the new animal drug are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved new animal drug and that the new animal drug can be expected to have the same therapeutic effect as the approved new animal drug when used in accordance with the labeling;
(vii) information submitted in the application is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for the approved new animal drug referred to in the application except for changes required because of differences approved under a petition filed under subsection (n)(3), because of a different withdrawal period, or because the drug and the approved new animal drug are produced or distributed by different manufacturers;
(viii) information submitted in the application or any other information available to the Secretary shows that (I) the inactive ingredients of the drug are unsafe for use under the conditions prescribed, recommended, or suggested in the labeling proposed for the drug, (II) the composition of the drug is unsafe under such conditions because of the type or quantity of inactive ingredients included or the manner in which the inactive ingredients are included, or (III) in the case of a drug for food producing animals, the inactive ingredients of the drug or its composition may be unsafe with respect to human food safety;
(ix) the approval under subsection (b)(1) of the approved new animal drug referred to in the application filed under subsection (b)(2) has been withdrawn or suspended for grounds described in paragraph (1) of subsection (e), the Secretary has published a notice of a hearing to withdraw approval of the approved new animal drug for such grounds, the approval under this paragraph of the new animal drug for which the application under subsection (b)(2) was filed has been withdrawn or suspended under subparagraph (G) for such grounds, or the Secretary has determined that the approved new animal drug has been withdrawn from sale for safety or effectiveness reasons;
(x) the application does not meet any other requirement of subsection (n); or
(xi) the application contains an untrue statement of material fact.
(B) If the Secretary finds that a new animal drug for which an application is submitted under subsection (b)(2) is bioequivalent to the approved new animal drug referred to in such application and that residues of the new animal drug are consistent with the tolerances established for such approved new animal drug but at a withdrawal period which is different than the withdrawal period approved for such approved new animal drug, the Secretary may establish, on the basis of information submitted, such different withdrawal period as the withdrawal period for the new animal drug for purposes of the approval of such application for such drug.
(C) Within 180 days of the initial receipt of an application under subsection (b)(2) or within such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall approve or disapprove the application.
(D) The approval of an application filed under subsection (b)(2) shall be made effective on the last applicable date determined under the following:
(i) If the applicant only made a certification described in clause (i) or (ii) of subsection (n)(1)(G) or in both such clauses, the approval may be made effective immediately.
(ii) If the applicant made a certification described in clause (iii) of subsection (n)(1)(G), the approval may be made effective on the date certified under clause (iii).
(iii) If the applicant made a certification described in clause (iv) of subsection (n)(1)(G), the approval shall be made effective immediately unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of 45 days from the date the notice provided under subsection (n)(2)(B)(i) is received. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the 30 month period beginning on the date of the receipt of the notice provided under subsection (n)(2)(B) or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that if before the expiration of such period—(I) the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of the court decision,(II) the court decides that such patent has been infringed, the approval shall be made effective on such date as the court orders under section 271(e)(4)(A) of title 35, or(III) the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of such court decision.
In such an action, each of the parties shall reasonably cooperate in expediting the action. Until the expiration of 45 days from the date the notice made under subsection (n)(2)(B) is received, no action may be brought under section 2201 of title 28 for a declaratory judgment with respect to the patent. Any action brought under section 2201 of title 28 shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business.
(iv) If the application contains a certification described in clause (iv) of subsection (n)(1)(G) and is for a drug for which a previous application has been filed under this subsection containing such a certification, the application shall be made effective not earlier than 180 days after—(I) the date the Secretary receives notice from the applicant under the previous application of the first commercial marketing of the drug under the previous application, or(II) the date of a decision of a court in an action described in subclause (III) 3
3 So in original. Probably should be “clause (iii)(III)”.
holding the patent which is the subject of the certification to be invalid or not infringed,
whichever is earlier.
(E) If the Secretary decides to disapprove an application, the Secretary shall give the applicant notice of an opportunity for a hearing before the Secretary on the question of whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within 30 days after such notice, such hearing shall commence not more than 90 days after the expiration of such 30 days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary’s order thereon shall be issued within 90 days after the date fixed by the Secretary for filing final briefs.
(F)
(i) If an application submitted under subsection (b)(1) for a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under subsection (b)(1), is approved after November 16, 1988, no application may be submitted under subsection (b)(2) which refers to the drug for which the subsection (b)(1) application was submitted before the expiration of 5 years from the date of the approval of the application under subsection (b)(1), except that such an application may be submitted under subsection (b)(2) after the expiration of 4 years from the date of the approval of the subsection (b)(1) application if it contains a certification of patent invalidity or noninfringement described in clause (iv) of subsection (n)(1)(G). The approval of such an application shall be made effective in accordance with subparagraph (B) except that, if an action for patent infringement is commenced during the one-year period beginning 48 months after the date of the approval of the subsection (b) application, the 30 month period referred to in subparagraph (D)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(ii) If an application submitted under subsection (b)(1) for a drug, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) that has been approved in another application approved under such subsection, is approved after November 16, 1988, and if such application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or, in the case of food producing animals, human food safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for minor uses or minor species) required for the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under subsection (b)(2) for the conditions of approval of such drug in the subsection (b)(1) application effective before the expiration of 3 years from the date of the approval of the application under subsection (b)(1) for such drug.
(iii) If a supplement to an application approved under subsection (b)(1) is approved after November 16, 1988, and the supplement contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or, in the case of food producing animals, human food safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for minor uses or minor species) required for the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under subsection (b)(2) for a change approved in the supplement effective before the expiration of 3 years from the date of the approval of the supplement.
(iv) An applicant under subsection (b)(1) who comes within the provisions of clause (i) of this subparagraph as a result of an application which seeks approval for a use solely in non-food producing animals, may elect, within 10 days of receiving such approval, to waive clause (i) of this subparagraph, in which event the limitation on approval of applications submitted under subsection (b)(2) set forth in clause (ii) of this subparagraph shall be applicable to the subsection (b)(1) application.
(v) If an application (including any supplement to a new animal drug application) submitted under subsection (b)(1) for a new animal drug for a food-producing animal use, which includes an active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) which has been the subject of a waiver under clause (iv) is approved after November 16, 1988, and if the application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or human food safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for minor uses or minor species) required for the new approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application (including any supplement to such application) submitted under subsection (b)(2) for the new conditions of approval of such drug in the subsection (b)(1) application effective before the expiration of five years from the date of approval of the application under subsection (b)(1) for such drug. The provisions of this paragraph shall apply only to the first approval for a food-producing animal use for the same applicant after the waiver under clause (iv).
(G) If an approved application submitted under subsection (b)(2) for a new animal drug refers to a drug the approval of which was withdrawn or suspended for grounds described in paragraph (1) or (2) of subsection (e) or was withdrawn or suspended under this subparagraph or which, as determined by the Secretary, has been withdrawn from sale for safety or effectiveness reasons, the approval of the drug under this paragraph shall be withdrawn or suspended—
(i) for the same period as the withdrawal or suspension under subsection (e) or this subparagraph, or
(ii) if the approved new animal drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
(H) For purposes of this paragraph:
(i) The term “bioequivalence” means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a new animal drug and becomes available at the site of drug action.
(ii) A new animal drug shall be considered to be bioequivalent to the approved new animal drug referred to in its application under subsection (n) if—(I) the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the approved new animal drug referred to in the application when administered at the same dose of the active ingredient under similar experimental conditions in either a single dose or multiple doses;(II) the extent of absorption of the drug does not show a significant difference from the extent of absorption of the approved new animal drug referred to in the application when administered at the same dose of the active ingredient under similar experimental conditions in either a single dose or multiple doses and the difference from the approved new animal drug in the rate of absorption of the drug is intentional, is reflected in its proposed labeling, is not essential to the attainment of effective drug concentrations in use, and is considered scientifically insignificant for the drug in attaining the intended purposes of its use and preserving human food safety; or(III) in any case in which the Secretary determines that the measurement of the rate and extent of absorption or excretion of the new animal drug in biological fluids is inappropriate or impractical, an appropriate acute pharmacological effects test or other test of the new animal drug and, when deemed scientifically necessary, of the approved new animal drug referred to in the application in the species to be tested or in an appropriate animal model does not show a significant difference between the new animal drug and such approved new animal drug when administered at the same dose under similar experimental conditions.
If the approved new animal drug referred to in the application for a new animal drug under subsection (n) is approved for use in more than one animal species, the bioequivalency information described in subclauses (I), (II), and (III) shall be obtained for one species, or if the Secretary deems appropriate based on scientific principles, shall be obtained for more than one species. The Secretary may prescribe the dose to be used in determining bioequivalency under subclause (I), (II), or (III). To assure that the residues of the new animal drug will be consistent with the established tolerances for the approved new animal drug referred to in the application under subsection (b)(2) upon the expiration of the withdrawal period contained in the application for the new animal drug, the Secretary shall require bioequivalency data or residue depletion studies of the new animal drug or such other data or studies as the Secretary considers appropriate based on scientific principles. If the Secretary requires one or more residue studies under the preceding sentence, the Secretary may not require that the assay methodology used to determine the withdrawal period of the new animal drug be more rigorous than the methodology used to determine the withdrawal period for the approved new animal drug referred to in the application. If such studies are required and if the approved new animal drug, referred to in the application for the new animal drug for which such studies are required, is approved for use in more than one animal species, such studies shall be conducted for one species, or if the Secretary deems appropriate based on scientific principles, shall be conducted for more than one species.
(3) If the patent information described in subsection (b)(1) could not be filed with the submission of an application under subsection (b)(1) because the application was filed before the patent information was required under subsection (b)(1) or a patent was issued after the application was approved under such subsection, the holder of an approved application shall file with the Secretary the patent number and the expiration date of any patent which claims the new animal drug for which the application was filed or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If the holder of an approved application could not file patent information under subsection (b)(1) because it was not required at the time the application was approved, the holder shall file such information under this subsection not later than 30 days after November 16, 1988, and if the holder of an approved application could not file patent information under subsection (b)(1) because no patent had been issued when an application was filed or approved, the holder shall file such information under this subsection not later than 30 days after the date the patent involved is issued. Upon the submission of patent information under this subsection, the Secretary shall publish it.
(4) A drug manufactured in a pilot or other small facility may be used to demonstrate the safety and effectiveness of the drug and to obtain approval for the drug prior to manufacture of the drug in a larger facility, unless the Secretary makes a determination that a full scale production facility is necessary to ensure the safety or effectiveness of the drug.
(d) Grounds for refusing application; approval of application; factors; “substantial evidence” defined; combination drugs
(1) If the Secretary finds, after due notice to the applicant in accordance with subsection (c) and giving him an opportunity for a hearing, in accordance with said subsection, that—
(A) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b), do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof;
(B) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions;
(C) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity;
(D) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions;
(E) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(F) upon the basis of information submitted to the Secretary as part of the application or any other information before the Secretary with respect to such drug, any use prescribed, recommended, or suggested in labeling proposed for such drug will result in a residue of such drug in excess of a tolerance found by the Secretary to be safe for such drug;
(G) the application failed to contain the patent information prescribed by subsection (b)(1);
(H) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; or
(I) such drug induces cancer when ingested by man or animal or, after tests which are appropriate for the evaluation of the safety of such drug, induces cancer in man or animal, except that the foregoing provisions of this subparagraph shall not apply with respect to such drug if the Secretary finds that, under the conditions of use specified in proposed labeling and reasonably certain to be followed in practice (i) such drug will not adversely affect the animals for which it is intended, and (ii) no residue of such drug will be found (by methods of examination prescribed or approved by the Secretary by regulations, which regulations shall not be subject to subsections (c), (d), and (h)), in any edible portion of such animals after slaughter or in any food yielded by or derived from the living animals;
he shall issue an order refusing to approve the application. If, after such notice and opportunity for hearings, the Secretary finds that subparagraphs (A) through (I) do not apply, he shall issue an order approving the application.
(2) In determining whether such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof, the Secretary shall consider, among other relevant factors, (A) the probable consumption of such drug and of any substance formed in or on food because of the use of such drug, (B) the cumulative effect on man or animal of such drug, taking into account any chemically or pharmacologically related substance, (C) safety factors which in the opinion of experts, qualified by scientific training and experience to evaluate the safety of such drugs, are appropriate for the use of animal experimentation data, and (D) whether the conditions of use prescribed, recommended, or suggested in the proposed labeling are reasonably certain to be followed in practice. Any order issued under this subsection refusing to approve an application shall state the findings upon which it is based.
(3) As used in this section, the term “substantial evidence” means evidence consisting of one or more adequate and well controlled investigations, such as—
(A) a study in a target species;
(B) a study in laboratory animals;
(C) any field investigation that may be required under this section and that meets the requirements of subsection (b)(3) if a presubmission conference is requested by the applicant;
(D) a bioequivalence study; or
(E) an in vitro study;
by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and reasonably be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.
(4) In a case in which an animal drug contains more than one active ingredient, or the labeling of the drug prescribes, recommends, or suggests use of the drug in combination with one or more other animal drugs, and the active ingredients or drugs intended for use in the combination have previously been separately approved pursuant to an application submitted under subsection (b)(1) for particular uses and conditions of use for which they are intended for use in the combination—
(A) the Secretary shall not issue an order under paragraph (1)(A), (1)(B), or (1)(D) refusing to approve the application for such combination on human food safety grounds unless the Secretary finds that the application fails to establish that—
(i) none of the active ingredients or drugs intended for use in the combination, respectively, at the longest withdrawal time of any of the active ingredients or drugs in the combination, respectively, exceeds its established tolerance; or
(ii) none of the active ingredients or drugs in the combination interferes with the methods of analysis for another of the active ingredients or drugs in the combination, respectively;
(B) the Secretary shall not issue an order under paragraph (1)(A), (1)(B), or (1)(D) refusing to approve the application for such combination on target animal safety grounds unless the Secretary finds that—
(i)(I) there is a substantiated scientific issue, specific to one or more of the active ingredients or animal drugs in the combination, that cannot adequately be evaluated based on information contained in the application for the combination (including any investigations, studies, or tests for which the applicant has a right of reference or use from the person by or for whom the investigations, studies, or tests were conducted); or(II) there is a scientific issue raised by target animal observations contained in studies submitted to the Secretary as part of the application; and
(ii) based on the Secretary’s evaluation of the information contained in the application with respect to the issues identified in clauses (i)(I) and (II), paragraph (1)(A), (B), or (D) apply;
(C) except in the case of a combination that contains a nontopical antibacterial ingredient or animal drug, the Secretary shall not issue an order under paragraph (1)(E) refusing to approve an application for a combination animal drug intended for use other than in animal feed or drinking water unless the Secretary finds that the application fails to demonstrate that—
(i) there is substantial evidence that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to labeled effectiveness;
(ii) each active ingredient or animal drug intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target population; or
(iii) where based on scientific information the Secretary has reason to believe the active ingredients or animal drugs may be physically incompatible or have disparate dosing regimens, such active ingredients or animal drugs are physically compatible or do not have disparate dosing regimens; and
(D) the Secretary shall not issue an order under paragraph (1)(E) refusing to approve an application for a combination animal drug intended for use in animal feed or drinking water unless the Secretary finds that the application fails to demonstrate that—
(i) there is substantial evidence that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to the labeled effectiveness;
(ii) each of the active ingredients or animal drugs intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target population;
(iii) where a combination contains more than one nontopical antibacterial ingredient or animal drug, there is substantial evidence that each of the nontopical antibacterial ingredients or animal drugs makes a contribution to the labeled effectiveness, except that for purposes of this clause, antibacterial ingredient or animal drug does not include the ionophore or arsenical classes of animal drugs; or
(iv) where based on scientific information the Secretary has reason to believe the active ingredients or animal drugs intended for use in drinking water may be physically incompatible, such active ingredients or animal drugs intended for use in drinking water are physically compatible.
(5) In reviewing an application that proposes a change to add an intended use for a minor use or a minor species to an approved new animal drug application, the Secretary shall reevaluate only the relevant information in the approved application to determine whether the application for the minor use or minor species can be approved. A decision to approve the application for the minor use or minor species is not, implicitly or explicitly, a reaffirmation of the approval of the original application.
(e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to health of man or animals
(1) The Secretary shall, after due notice and opportunity for hearing to the applicant, issue an order withdrawing approval of an application filed pursuant to subsection (b) with respect to any new animal drug if the Secretary finds—
(A) that experience or scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved or the condition of use authorized under subsection (a)(4)(A);
(B) that new evidence not contained in such application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved or that subparagraph (I) of paragraph (1) of subsection (d) applies to such drug;
(C) on the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that such drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(D) the patent information prescribed by subsection (c)(3) was not filed within 30 days after the receipt of written notice from the Secretary specifying the failure to file such information;
(E) that the application contains any untrue statement of a material fact; or
(F) that the applicant has made any changes from the standpoint of safety or effectiveness beyond the variations provided for in the application unless he has supplemented the application by filing with the Secretary adequate information respecting all such changes and unless there is in effect an approval of the supplemental application. The supplemental application shall be treated in the same manner as the original application.
If the Secretary (or in his absence the officer acting as Secretary) finds that there is an imminent hazard to the health of man or of the animals for which such drug is intended, he may suspend the approval of such application immediately, and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this sentence to suspend the approval of an application shall not be delegated.
(2) The Secretary may also, after due notice and opportunity for hearing to the applicant, issue an order withdrawing the approval of an application with respect to any new animal drug under this section if the Secretary finds—
(A) that the applicant has failed to establish a system for maintaining required rec­ords, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under subsection (l), or the applicant has refused to permit access to, or copying or verification of, such records as required by paragraph (2) of such subsection;
(B) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or
(C) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the labeling of such drug, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of.
(3) Any order under this subsection shall state the findings upon which it is based.
(f) Revocation of order refusing, withdrawing or suspending approval of application
(g) Service of orders
(h) Appeal from order
(i) Publication in Federal Register; effective date and revocation or suspension of regulation
(j) Exemption of drugs for research; discretionary and mandatory conditions
(k) Food containing new animal drug considered unadulterated while approval of application for such drug is effective
(l) Records and reports; required information; regulations and orders; examination of data; access to records
(1) In the case of any new animal drug for which an approval of an application filed pursuant to subsection (b) or section 360ccc of this title is in effect, the applicant shall establish and maintain such records, and make such reports to the Secretary, of data relating to experience, including experience with uses authorized under subsection (a)(4)(A), and other data or information, received or otherwise obtained by such applicant with respect to such drug, or with respect to animal feeds bearing or containing such drug, as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e) or subsection (m)(4) of this section. Such regulation or order shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom such regulation or order is applicable, of similar information received or otherwise obtained by the Secretary.
(2) Every person required under this subsection to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(3)
(A) In the case of each new animal drug described in paragraph (1) that contains an antimicrobial active ingredient, the sponsor of the drug shall submit an annual report to the Secretary on the amount of each antimicrobial active ingredient in the drug that is sold or distributed for use in food-producing animals, including information on any distributor-labeled product.
(B) Each report under this paragraph shall specify the amount of each antimicrobial active ingredient—
(i) by container size, strength, and dosage form;
(ii) by quantities distributed domestically and quantities exported; and
(iii) by dosage form, including, for each such dosage form, a listing of the target animals, indications, and production classes that are specified on the approved label of the product.
(C) Each report under this paragraph shall—
(i) be submitted not later than March 31 each year;
(ii) cover the period of the preceding calendar year; and
(iii) include separate information for each month of such calendar year.
(D) The Secretary may share information reported under this paragraph with the Antimicrobial Resistance Task Force established under section 247d–5 of title 42.
(E) The Secretary shall make summaries of the information reported under this paragraph publicly available, except that—
(i) the summary data shall be reported by antimicrobial class, and no class with fewer than 3 distinct sponsors of approved applications shall be independently reported; and
(ii) the data shall be reported in a manner consistent with protecting both national security and confidential business information.
(m) Feed mill licenses
(1) Any person may file with the Secretary an application for a license to manufacture animal feeds bearing or containing new animal drugs. Such person shall submit to the Secretary as part of the application (A) a full statement of the business name and address of the specific facility at which the manufacturing is to take place and the facility’s registration number, (B) the name and signature of the responsible individual or individuals for that facility, (C) a certification that the animal feeds bearing or containing new animal drugs are manufactured and labeled in accordance with the applicable regulations published pursuant to subsection (i) or for indexed new animal drugs in accordance with the index listing published pursuant to section 360ccc–1(e)(2) of this title and the labeling requirements set forth in section 360ccc–1(h) of this title, and (D) a certification that the methods used in, and the facilities and controls used for, manufacturing, processing, packaging, and holding such animal feeds are in conformity with current good manufacturing practice as described in section 351(a)(2)(B) of this title.
(2) Within 90 days after the filing of an application pursuant to paragraph (1), or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall (A) issue an order approving the application if the Secretary then finds that none of the grounds for denying approval specified in paragraph (3) applies, or (B) give the applicant notice of an opportunity for a hearing before the Secretary under paragraph (3) on the question whether such application is approvable. The procedure governing such a hearing shall be the procedure set forth in the last two sentences of subsection (c)(1).
(3) If the Secretary, after due notice to the applicant in accordance with paragraph (2) and giving the applicant an opportunity for a hearing in accordance with such paragraph, finds, on the basis of information submitted to the Secretary as part of the application, on the basis of a preapproval inspection, or on the basis of any other information before the Secretary—
(A) that the application is incomplete, false, or misleading in any particular;
(B) that the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such animal feed are inadequate to preserve the identity, strength, quality, and purity of the new animal drug therein; or
(C) that the facility manufactures animal feeds bearing or containing new animal drugs in a manner that does not accord with the specifications for manufacture or labels animal feeds bearing or containing new animal drugs in a manner that does not accord with the conditions or indications of use that are published pursuant to subsection (i) or an index listing pursuant to section 360ccc–1(e) of this title,
the Secretary shall issue an order refusing to approve the application. If, after such notice and opportunity for hearing, the Secretary finds that subparagraphs (A) through (C) do not apply, the Secretary shall issue an order approving the application. An order under this subsection approving an application for a license to manufacture animal feeds bearing or containing new animal drugs shall permit a facility to manufacture only those animal feeds bearing or containing new animal drugs for which there are in effect regulations pursuant to subsection (i) or an index listing pursuant to section 360ccc–1(e) of this title relating to the use of such drugs in or on such animal feed.
(4)
(A) The Secretary shall, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture animal feeds bearing or containing new animal drugs under this subsection if the Secretary finds—
(i) that the application for such license contains any untrue statement of a material fact; or
(ii) that the applicant has made changes that would cause the application to contain any untrue statements of material fact or that would affect the safety or effectiveness of the animal feeds manufactured at the facility unless the applicant has supplemented the application by filing with the Secretary adequate information respecting all such changes and unless there is in effect an approval of the supplemental application.
If the Secretary (or in the Secretary’s absence the officer acting as the Secretary) finds that there is an imminent hazard to the health of humans or of the animals for which such animal feed is intended, the Secretary may suspend the license immediately, and give the applicant prompt notice of the action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this sentence shall not be delegated.
(B) The Secretary may also, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture animal feed under this subsection if the Secretary finds—
(i) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under paragraph (5)(A) of this subsection or
(ii) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the methods used in, or the facilities and controls used for, the manufacture, processing, packing, and holding of such animal feed are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drug therein, and were not made adequate within a reasonable time after receipt of written notice from the Secretary, specifying the matter complained of;
(iii) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the labeling of any animal feeds, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or
(iv) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the facility has manufactured, processed, packed, or held animal feed bearing or containing a new animal drug adulterated under section 351(a)(6) of this title and the facility did not discontinue the manufacture, processing, packing, or holding of such animal feed within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of.
(C) The Secretary may also revoke a license to manufacture animal feeds under this subsection if an applicant gives notice to the Secretary of intention to discontinue the manufacture of all animal feed covered under this subsection and waives an opportunity for a hearing on the matter.
(D) Any order under this paragraph shall state the findings upon which it is based.
(5) When a license to manufacture animal feeds bearing or containing new animal drugs has been issued—
(A) the applicant shall establish and maintain such records, and make such reports to the Secretary, or (at the option of the Secretary) to the appropriate person or persons holding an approved application filed under subsection (b), as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e) or paragraph (4); and
(B) every person required under this subsection to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(6) To the extent consistent with the public health, the Secretary may promulgate regulations for exempting from the operation of this subsection facilities that manufacture, process, pack, or hold animal feeds bearing or containing new animal drugs.
(n) Abbreviated applications for new animal drugs; contents, filing, etc.; lists of approved drugs
(1) An abbreviated application for a new animal drug shall contain—
(A)
(i) except as provided in clause (ii), information to show that the conditions of use or similar limitations (whether in the labeling or published pursuant to subsection (i)) prescribed, recommended, or suggested in the labeling proposed for the new animal drug have been previously approved for a new animal drug listed under paragraph (4) (hereinafter in this subsection referred to as an “approved new animal drug”), and
(ii) information to show that the withdrawal period at which residues of the new animal drug will be consistent with the tolerances established for the approved new animal drug is the same as the withdrawal period previously established for the approved new animal drug or, if the withdrawal period is proposed to be different, information showing that the residues of the new animal drug at the proposed different withdrawal period will be consistent with the tolerances established for the approved new animal drug;
(B)
(i) information to show that the active ingredients of the new animal drug are the same as those of the approved new animal drug, and
(ii) if the approved new animal drug has more than one active ingredient, and if one of the active ingredients of the new animal drug is different from one of the active ingredients of the approved new animal drug and the application is filed pursuant to the approval of a petition filed under paragraph (3)—(I) information to show that the other active ingredients of the new animal drug are the same as the active ingredients of the approved new animal drug,(II) information to show either that the different active ingredient is an active ingredient of another approved new animal drug or of an animal drug which does not meet the requirements of section 321(v) of this title, and(III) such other information respecting the different active ingredients as the Secretary may require;
(C)
(i) if the approved new animal drug is permitted to be used with one or more animal drugs in animal feed, information to show that the proposed uses of the new animal drug with other animal drugs in animal feed are the same as the uses of the approved new animal drug, and
(ii) if the approved new animal drug is permitted to be used with one or more other animal drugs in animal feed, and one of the other animal drugs proposed for use with the new animal drug in animal feed is different from one of the other animal drugs permitted to be used in animal feed with the approved new animal drug, and the application is filed pursuant to the approval of a petition filed under paragraph (3)—(I) information to show either that the different animal drug proposed for use with the approved new animal drug in animal feed is an approved new animal drug permitted to be used in animal feed or does not meet the requirements of section 321(v) of this title when used with another animal drug in animal feed,(II) information to show that other animal drugs proposed for use with the new animal drug in animal feed are the same as the other animal drugs permitted to be used with the approved new animal drug, and(III) such other information respecting the different animal drug or combination with respect to which the petition was filed as the Secretary may require,
(D) information to show that the route of administration, the dosage form, and the strength of the new animal drug are the same as those of the approved new animal drug or, if the route of administration, the dosage form, or the strength of the new animal drug is different and the application is filed pursuant to the approval of a petition filed under paragraph (3), such information respecting the route of administration, dosage form, or strength with respect to which the petition was filed as the Secretary may require;
(E) information to show that the new animal drug is bioequivalent to the approved new animal drug, except that if the application is filed pursuant to the approval of a petition filed under paragraph (3) for the purposes described in subparagraph (B) or (C), information to show that the active ingredients of the new animal drug are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved new animal drug and that the new animal drug can be expected to have the same therapeutic effect as the approved new animal drug when used in accordance with the labeling;
(F) information to show that the labeling proposed for the new animal drug is the same as the labeling approved for the approved new animal drug except for changes required because of differences approved under a petition filed under paragraph (3), because of a different withdrawal period, or because the new animal drug and the approved new animal drug are produced or distributed by different manufacturers;
(G) the items specified in clauses (B) through (F) of subsection (b)(1);
(H) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the approved new animal drug or which claims a use for such approved new animal drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection (b)(1) or (c)(3)—
(i) that such patent information has not been filed,
(ii) that such patent has expired,
(iii) of the date on which such patent will expire, or
(iv) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new animal drug for which the application is filed; and
(I) if with respect to the approved new animal drug information was filed under subsection (b)(1) or (c)(3) for a method of use patent which does not claim a use for which the applicant is seeking approval of an application under subsection (c)(2), a statement that the method of use patent does not claim such a use.
The Secretary may not require that an abbreviated application contain information in addition to that required by subparagraphs (A) through (I).
(2)
(A) An applicant who makes a certification described in paragraph (1)(G)(iv) shall include in the application a statement that the applicant will give the notice required by subparagraph (B) to—
(i) each owner of the patent which is the subject of the certification or the representative of such owner designated to receive such notice, and
(ii) the holder of the approved application under subsection (c)(1) for the drug which is claimed by the patent or a use of which is claimed by the patent or the representative of such holder designated to receive such notice.
(B) The notice referred to in subparagraph (A) shall state that an application, which contains data from bioequivalence studies, has been filed under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of such drug before the expiration of the patent referred to in the certification. Such notice shall include a detailed statement of the factual and legal basis of the applicant’s opinion that the patent is not valid or will not be infringed.
(C) If an application is amended to include a certification described in paragraph (1)(G)(iv), the notice required by subparagraph (B) shall be given when the amended application is filed.
(3) If a person wants to submit an abbreviated application for a new animal drug—
(A) whose active ingredients, route of administration, dosage form, or strength differ from that of an approved new animal drug, or
(B) whose use with other animal drugs in animal feed differs from that of an approved new animal drug,
such person shall submit a petition to the Secretary seeking permission to file such an application. The Secretary shall approve a petition for a new animal drug unless the Secretary finds that—
(C) investigations must be conducted to show the safety and effectiveness, in animals to be treated with the drug, of the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed which differ from the approved new animal drug, or
(D) investigations must be conducted to show the safety for human consumption of any residues in food resulting from the proposed active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed for the new animal drug which is different from the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed of the approved new animal drug.
The Secretary shall approve or disapprove a petition submitted under this paragraph within 90 days of the date the petition is submitted.
(4)
(A)
(i) Within 60 days of November 16, 1988, the Secretary shall publish and make available to the public a list in alphabetical order of the official and proprietary name of each new animal drug which has been approved for safety and effectiveness before November 16, 1988.
(ii) Every 30 days after the publication of the first list under clause (i) the Secretary shall revise the list to include each new animal drug which has been approved for safety and effectiveness under subsection (c) during the 30 day period.
(iii) When patent information submitted under subsection (b)(1) or (c)(3) respecting a new animal drug included on the list is to be published by the Secretary, the Secretary shall, in revisions made under clause (ii), include such information for such drug.
(B) A new animal drug approved for safety and effectiveness before November 16, 1988, or approved for safety and effectiveness under subsection (c) shall, for purposes of this subsection, be considered to have been published under subparagraph (A) on the date of its approval or November 16, 1988, whichever is later.
(C) If the approval of a new animal drug was withdrawn or suspended under subsection (c)(2)(G) or for grounds described in subsection (e) or if the Secretary determines that a drug has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under subparagraph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list—
(i) for the same period as the withdrawal or suspension under subsection (c)(2)(G) or (e), or
(ii) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
A notice of the removal shall be published in the Federal Register.
(5) If an application contains the information required by clauses (A), (G), and (H) of subsection (b)(1) and such information—
(A) is relied on by the applicant for the approval of the application, and
(B) is not information derived either from investigations, studies, or tests conducted by or for the applicant or for which the applicant had obtained a right of reference or use from the person by or for whom the investigations, studies, or tests were conducted,
such application shall be considered to be an application filed under subsection (b)(2).
(o) “Patent” defined
(p) Safety and effectiveness data
(1) Safety and effectiveness data and information which has been submitted in an application filed under subsection (b)(1) or section 360ccc(a) of this title for a drug and which has not previously been disclosed to the public shall be made available to the public, upon request, unless extraordinary circumstances are shown—
(A) if no work is being or will be undertaken to have the application approved,
(B) if the Secretary has determined that the application is not approvable and all legal appeals have been exhausted,
(C) if approval of the application under subsection (c) is withdrawn and all legal appeals have been exhausted,
(D) if the Secretary has determined that such drug is not a new drug, or
(E) upon the effective date of the approval of the first application filed under subsection (b)(2) which refers to such drug or upon the date upon which the approval of an application filed under subsection (b)(2) which refers to such drug could be made effective if such an application had been filed.
(2) Any request for data and information pursuant to paragraph (1) shall include a verified statement by the person making the request that any data or information received under such paragraph shall not be disclosed by such person to any other person—
(A) for the purpose of, or as part of a plan, scheme, or device for, obtaining the right to make, use, or market, or making, using, or marketing, outside the United States, the drug identified in the application filed under subsection (b)(1) or section 360ccc(a) of this title, and
(B) without obtaining from any person to whom the data and information are disclosed an identical verified statement, a copy of which is to be provided by such person to the Secretary, which meets the requirements of this paragraph.
(q) Date of approval in the case of recommended controls under the CSA
(1) In general
(2) Date of approvalFor purposes of this section, with respect to an application described in paragraph (1), the term “date of approval” shall mean the later of—
(A) the date an application under subsection (b) is approved under subsection (c); or
(B) the date of issuance of the interim final rule controlling the drug.
(June 25, 1938, ch. 675, § 512, as added Pub. L. 90–399, § 101(b), July 13, 1968, 82 Stat. 343; amended Pub. L. 100–670, title I, §§ 101, 102, 104, 107(a)(2), Nov. 16, 1988, 102 Stat. 3971, 3981, 3982, 3984; Pub. L. 102–108, § 2(e), Aug. 17, 1991, 105 Stat. 550; Pub. L. 103–80, § 3(r), Aug. 13, 1993, 107 Stat. 777; Pub. L. 103–396, § 2(a), (b)(2), (3), Oct. 22, 1994, 108 Stat. 4153, 4154; Pub. L. 104–250, §§ 2(a)–(d), 3, 4, 5(c), 6(a), (b), Oct. 9, 1996, 110 Stat. 3151–3153, 3155–3157; Pub. L. 105–115, title I, § 124(b), Nov. 21, 1997, 111 Stat. 2325; Pub. L. 105–277, div. A, § 101(a) [title VII, § 737], Oct. 21, 1998, 112 Stat. 2681, 2681–30; Pub. L. 106–113, div. B, § 1000(a)(9) [title IV, § 4732(b)(11)], Nov. 29, 1999, 113 Stat. 1536, 1501A–584; Pub. L. 108–282, title I, § 102(b)(2), (3), (5)(I)–(S), Aug. 2, 2004, 118 Stat. 892, 903, 904; Pub. L. 110–316, title I, § 105(a), Aug. 14, 2008, 122 Stat. 3513; Pub. L. 114–89, § 2(a)(3)(A), Nov. 25, 2015, 129 Stat. 699; Pub. L. 114–255, div. A, title III, § 3088(b), Dec. 13, 2016, 130 Stat. 1149; Pub. L. 115–234, title III, § 301(a), Aug. 14, 2018, 132 Stat. 2436; Pub. L. 117–9, § 1(a)(2), Apr. 23, 2021, 135 Stat. 257.)

CITE AS: 21 USC 360b

§ 360b–1. Priority zoonotic animal drugs
(a) In general
(b) Request for designation
(c) Designation
(1) In general
(2) Actions
The actions to expedite the development and review of an application under paragraph (1) may include, as appropriate—
(A) taking steps to ensure that the design of clinical trials is as efficient as practicable, when scientifically appropriate, such as by utilizing novel trial designs or drug development tools (including biomarkers) that may reduce the number of animals needed for studies;
(B) providing timely advice to, and interactive communication with, the sponsor (which may include meetings with the sponsor and review team) regarding the development of the new animal drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable;
(C) involving senior managers and review staff with experience in zoonotic or vector-borne disease to facilitate collaborative, cross-disciplinary review, including, as appropriate, across agency centers; and
(D) implementing additional administrative or process enhancements, as necessary, to facilitate an efficient review and development program.
(June 25, 1938, ch. 675, § 512A, as added Pub. L. 116–136, div. A, title III, § 3302, Mar. 27, 2020, 134 Stat. 384.)

CITE AS: 21 USC 360b-1

§ 360c. Classification of devices intended for human use
(a) Classes of devices
(1) There are established the following classes of devices intended for human use:
(A)Class I, General Controls.—
(i) A device for which the controls authorized by or under section 351, 352, 360, 360f, 360h, 360i, or 360j of this title or any combination of such sections are sufficient to provide reasonable assurance of the safety and effectiveness of the device.
(ii) A device for which insufficient information exists to determine that the controls referred to in clause (i) are sufficient to provide reasonable assurance of the safety and effectiveness of the device or to establish special controls to provide such assurance, but because it—(I) is not purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, and(II) does not present a potential unreasonable risk of illness or injury,
is to be regulated by the controls referred to in clause (i).
(B)Class II, Special Controls.—A device which cannot be classified as a class I device because the general controls by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of the device, and for which there is sufficient information to establish special controls to provide such assurance, including the promulgation of performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines (including guidelines for the submission of clinical data in premarket notification submissions in accordance with section 360(k) of this title), recommendations, and other appropriate actions as the Secretary deems necessary to provide such assurance. For a device that is purported or represented to be for a use in supporting or sustaining human life, the Secretary shall examine and identify the special controls, if any, that are necessary to provide adequate assurance of safety and effectiveness and describe how such controls provide such assurance.
(C)Class III, Premarket Approval.—A device which because—
(i) it (I) cannot be classified as a class I device because insufficient information exists to determine that the application of general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device, and (II) cannot be classified as a class II device because insufficient information exists to determine that the special controls described in subparagraph (B) would provide reasonable assurance of its safety and effectiveness, and
(ii)(I) is purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, or(II) presents a potential unreasonable risk of illness or injury,
is to be subject, in accordance with section 360e of this title, to premarket approval to provide reasonable assurance of its safety and effectiveness.
If there is not sufficient information to establish a performance standard for a device to provide reasonable assurance of its safety and effectiveness, the Secretary may conduct such activities as may be necessary to develop or obtain such information.
(2) For purposes of this section and sections 360d and 360e of this title, the safety and effectiveness of a device are to be determined—
(A) with respect to the persons for whose use the device is represented or intended,
(B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and
(C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use.
(3)
(A) Except as authorized by subparagraph (B), the effectiveness of a device is, for purposes of this section and sections 360d and 360e of this title, to be determined, in accordance with regulations promulgated by the Secretary, on the basis of well-controlled investigations, including 1 or more clinical investigations where appropriate, by experts qualified by training and experience to evaluate the effectiveness of the device, from which investigations it can fairly and responsibly be concluded by qualified experts that the device will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling of the device.
(B) If the Secretary determines that there exists valid scientific evidence (other than evidence derived from investigations described in subparagraph (A))—
(i) which is sufficient to determine the effectiveness of a device, and
(ii) from which it can fairly and responsibly be concluded by qualified experts that the device will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling of the device,
then, for purposes of this section and sections 360d and 360e of this title, the Secretary may authorize the effectiveness of the device to be determined on the basis of such evidence.
(C) In making a determination of a reasonable assurance of the effectiveness of a device for which an application under section 360e of this title has been submitted, the Secretary shall consider whether the extent of data that otherwise would be required for approval of the application with respect to effectiveness can be reduced through reliance on postmarket controls.
(D)
(i) The Secretary, upon the written request of any person intending to submit an application under section 360e of this title, shall meet with such person to determine the type of valid scientific evidence (within the meaning of subparagraphs (A) and (B)) that will be necessary to demonstrate for purposes of approval of an application the effectiveness of a device for the conditions of use proposed by such person. The written request shall include a detailed description of the device, a detailed description of the proposed conditions of use of the device, a proposed plan for determining whether there is a reasonable assurance of effectiveness, and, if available, information regarding the expected performance from the device. Within 30 days after such meeting, the Secretary shall specify in writing the type of valid scientific evidence that will provide a reasonable assurance that a device is effective under the conditions of use proposed by such person.
(ii) Any clinical data, including one or more well-controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device effectiveness shall be specified as result of a determination by the Secretary that such data are necessary to establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval.
(iii) For purposes of clause (ii), the term “necessary” means the minimum required information that would support a determination by the Secretary that an application provides reasonable assurance of the effectiveness of the device.
(iv) Nothing in this subparagraph shall alter the criteria for evaluating an application for premarket approval of a device.
(v) The determination of the Secretary with respect to the specification of valid scientific evidence under clauses (i) and (ii) shall be binding upon the Secretary, unless such determination by the Secretary could be contrary to the public health.
(b) Classification panels
(1) For purposes of—
(A) determining which devices intended for human use should be subject to the requirements of general controls, performance standards, or premarket approval, and
(B) providing notice to the manufacturers and importers of such devices to enable them to prepare for the application of such requirements to devices manufactured or imported by them,
the Secretary shall classify all such devices (other than devices classified by subsection (f)) into the classes established by subsection (a). For the purpose of securing recommendations with respect to the classification of devices, the Secretary shall establish panels of experts or use panels of experts established before May 28, 1976, or both. Section 1013 of title 5 shall not apply to the duration of a panel established under this paragraph.
(2) The Secretary shall appoint to each panel established under paragraph (1) persons who are qualified by training and experience to evaluate the safety and effectiveness of the devices to be referred to the panel and who, to the extent feasible, possess skill in the use of, or experience in the development, manufacture, or utilization of, such devices. The Secretary shall make appointments to each panel so that each panel shall consist of members with adequately diversified expertise in such fields as clinical and administrative medicine, engineering, biological and physical sciences, and other related professions. In addition, each panel shall include as nonvoting members a representative of consumer interests and a representative of interests of the device manufacturing industry. Scientific, trade, and consumer organizations shall be afforded an opportunity to nominate individuals for appointment to the panels. No individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter may be a member of any panel. The Secretary shall designate one of the members of each panel to serve as chairman thereof.
(3) Panel members (other than officers or employees of the United States), while attending meetings or conferences of a panel or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, but not at rates exceeding the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day so engaged, including traveltime; and while so serving away from their homes or regular places of business each member may be allowed travel expenses (including per diem in lieu of subsistence) as authorized by section 5703 of title 5, for persons in the Government service employed intermittently.
(4) The Secretary shall furnish each panel with adequate clerical and other necessary assistance.
(5)
(A) Classification panels covering each type of device shall be scheduled to meet at such times as may be appropriate for the Secretary to meet applicable statutory deadlines.
(B) When a device is specifically the subject of review by a classification panel, the Secretary shall—
(i) ensure that adequate expertise is represented on the classification panel to assess—(I) the disease or condition which the device is intended to cure, treat, mitigate, prevent, or diagnose; and(II) the technology of the device; and
(ii) provide an opportunity for the person whose device is specifically the subject of panel review to provide recommendations on the expertise needed among the voting members of the panel.
(C) For purposes of subparagraph (B)(i), the term “adequate expertise” means that the membership of the classification panel includes—
(i) two or more voting members, with a specialty or other expertise clinically relevant to the device under review; and
(ii) at least one voting member who is knowledgeable about the technology of the device.
(D) The Secretary shall provide an annual opportunity for patients, representatives of patients, and sponsors of medical devices that may be specifically the subject of a review by a classification panel to provide recommendations for individuals with appropriate expertise to fill voting member positions on classification panels.
(6)
(A) Any person whose device is specifically the subject of review by a classification panel shall have—
(i) the same access to data and information submitted to a classification panel (except for data and information that are not available for public disclosure under section 552 of title 5) as the Secretary;
(ii) the opportunity to submit, for review by a classification panel, information that is based on the data or information provided in the application submitted under section 360e of this title by the person, which information shall be submitted to the Secretary for prompt transmittal to the classification panel; and
(iii) the same opportunity as the Secretary to participate in meetings of the panel, including, subject to the discretion of the panel chairperson, by designating a representative who will be provided a time during the panel meeting to address the panel for the purpose of correcting misstatements of fact or providing clarifying information, and permitting the person or representative to call on experts within the person’s organization to address such specific issues in the time provided.
(B)
(i) Any meeting of a classification panel with respect to the review of a device shall—(I) provide adequate time for initial presentations by the person whose device is specifically the subject of such review and by the Secretary; and(II) encourage free and open participation by all interested persons.
(ii) Following the initial presentations described in clause (i), the panel may—(I) pose questions to a designated representative described in subparagraph (A)(iii); and(II) consider the responses to such questions in the panel’s review of the device.
(7) After receiving from a classification panel the conclusions and recommendations of the panel on a matter that the panel has reviewed, the Secretary shall review the conclusions and recommendations, shall make a final decision on the matter in accordance with section 360e(d)(2) of this title, and shall notify the affected persons of the decision in writing and, if the decision differs from the conclusions and recommendations of the panel, shall include the reasons for the difference.
(8) A classification panel under this subsection shall not be subject to the annual chartering and annual report requirements of the 1
1 So in original. The word “the” probably should not appear.
chapter 10 of title 5.
(c) Classification panel organization and operation
(1) The Secretary shall organize the panels according to the various fields of clinical medicine and fundamental sciences in which devices intended for human use are used. The Secretary shall refer a device to be classified under this section to an appropriate panel established or authorized to be used under subsection (b) for its review and for its recommendation respecting the classification of the device. The Secretary shall by regulation prescribe the procedure to be followed by the panels in making their reviews and recommendations. In making their reviews of devices, the panels, to the maximum extent practicable, shall provide an opportunity for interested persons to submit data and views on the classification of the devices.
(2)
(A) Upon completion of a panel’s review of a device referred to it under paragraph (1), the panel shall, subject to subparagraphs (B) and (C), submit to the Secretary its recommendation for the classification of the device. Any such recommendation shall (i) contain (I) a summary of the reasons for the recommendation, (II) a summary of the data upon which the recommendation is based, and (III) an identification of the risks to health (if any) presented by the device with respect to which the recommendation is made, and (ii) to the extent practicable, include a recommendation for the assignment of a priority for the application of the requirements of section 360d or 360e of this title to a device recommended to be classified in class II or class III.
(B) A recommendation of a panel for the classification of a device in class I shall include a recommendation as to whether the device should be exempted from the requirements of section 360, 360i, or 360j(f) of this title.
(C) In the case of a device which has been referred under paragraph (1) to a panel, and which—
(i) is intended to be implanted in the human body or is purported or represented to be for a use in supporting or sustaining human life, and
(ii)(I) has been introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, or(II) is within a type of device which was so introduced or delivered before such date and is substantially equivalent to another device within that type,
such panel shall recommend to the Secretary that the device be classified in class III unless the panel determines that classification of the device in such class is not necessary to provide reasonable assurance of its safety and effectiveness. If a panel does not recommend that such a device be classified in class III, it shall in its recommendation to the Secretary for the classification of the device set forth the reasons for not recommending classification of the device in such class.
(3) The panels shall submit to the Secretary within one year of the date funds are first appropriated for the implementation of this section their recommendations respecting all devices of a type introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976.
(d) Panel recommendation; publication; priorities
(1) Upon receipt of a recommendation from a panel respecting a device, the Secretary shall publish in the Federal Register the panel’s recommendation and a proposed regulation classifying such device and shall provide interested persons an opportunity to submit comments on such recommendation and the proposed regulation. After reviewing such comments, the Secretary shall, subject to paragraph (2), by regulation classify such device.
(2)
(A) A regulation under paragraph (1) classifying a device in class I shall prescribe which, if any, of the requirements of section 360, 360i, or 360j(f) of this title shall not apply to the device. A regulation which makes a requirement of section 360, 360i, or 360j(f) of this title inapplicable to a device shall be accompanied by a statement of the reasons of the Secretary for making such requirement inapplicable.
(B) A device described in subsection (c)(2)(C) shall be classified in class III unless the Secretary determines that classification of the device in such class is not necessary to provide reasonable assurance of its safety and effectiveness. A proposed regulation under paragraph (1) classifying such a device in a class other than class III shall be accompanied by a full statement of the reasons of the Secretary (and supporting documentation and data) for not classifying such device in such class and an identification of the risks to health (if any) presented by such device.
(3) In the case of devices classified in class II and devices classified under this subsection in class III and described in section 360e(b)(1) of this title the Secretary may establish priorities which, in his discretion, shall be used in applying sections 360d and 360e of this title, as appropriate, to such devices.
(e) Classification changes
(1)
(A)
(i) Based on new information respecting a device, the Secretary may, upon the initiative of the Secretary or upon petition of an interested person, change the classification of such device, and revoke, on account of the change in classification, any regulation or requirement in effect under section 360d or 360e of this title with respect to such device, by administrative order published in the Federal Register following publication of a proposed reclassification order in the Federal Register, a meeting of a device classification panel described in subsection (b), and consideration of comments to a public docket, notwithstanding subchapter II of chapter 5 of title 5. The proposed reclassification order published in the Federal Register shall set forth the proposed reclassification, and a substantive summary of the valid scientific evidence concerning the proposed reclassification, including—(I) the public health benefit of the use of the device, and the nature and, if known, incidence of the risk of the device;(II) in the case of a reclassification from class II to class III, why general controls pursuant to subsection (a)(1)(A) and special controls pursuant to subsection (a)(1)(B) together are not sufficient to provide a reasonable assurance of safety and effectiveness for such device; and(III) in the case of reclassification from class III to class II, why general controls pursuant to subsection (a)(1)(A) and special controls pursuant to subsection (a)(1)(B) together are sufficient to provide a reasonable assurance of safety and effectiveness for such device.
(ii) An order under this subsection changing the classification of a device from class III to class II may provide that such classification shall not take effect until the effective date of a performance standard established under section 360d of this title for such device.
(B) Authority to issue such administrative order shall not be delegated below the Director of the Center for Devices and Radiological Health, acting in consultation with the Commissioner.
(2) By an order issued under paragraph (1), the Secretary may change the classification of a device from class III—
(A) to class II if the Secretary determines that special controls would provide reasonable assurance of the safety and effectiveness of the device and that general controls would not provide reasonable assurance of the safety and effectiveness of the device, or
(B) to class I if the Secretary determines that general controls would provide reasonable assurance of the safety and effectiveness of the device.
(f) Initial classification and reclassification of certain devices
(1) Any device intended for human use which was not introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, is classified in class III unless—
(A) the device—
(i) is within a type of device (I) which was introduced or delivered for introduction into interstate commerce for commercial distribution before such date and which is to be classified pursuant to subsection (b), or (II) which was not so introduced or delivered before such date and has been classified in class I or II, and
(ii) is substantially equivalent to another device within such type;
(B) the Secretary in response to a petition submitted under paragraph (3) has classified such device in class I or II; or
(C) the device is classified pursuant to a request submitted under paragraph (2).
A device classified in class III under this paragraph shall be classified in that class until the effective date of an order of the Secretary under paragraph (2) or (3) classifying the device in class I or II.
(2)
(A)
(i) Any person who submits a report under section 360(k) of this title for a type of device that has not been previously classified under this chapter, and that is classified into class III under paragraph (1), may request, after receiving written notice of such a classification, the Secretary to classify the device.
(ii) In lieu of submitting a report under section 360(k) of this title and submitting a request for classification under clause (i) for a device, if a person determines there is no legally marketed device upon which to base a determination of substantial equivalence (as defined in subsection (i)), a person may submit a request under this clause for the Secretary to classify the device.
(iii) Upon receipt of a request under clause (i) or (ii), the Secretary shall classify the device subject to the request under the criteria set forth in subparagraphs (A) through (C) of subsection (a)(1) within 120 days.
(iv) Notwithstanding clause (iii), the Secretary may decline to undertake a classification request submitted under clause (ii) if the Secretary identifies a legally marketed device that could provide a reasonable basis for review of substantial equivalence under paragraph (1), or when the Secretary determines that the device submitted is not of low to moderate risk or that general controls would be inadequate to control the risks and special controls to mitigate the risks cannot be developed.
(v) The person submitting the request for classification under this subparagraph may recommend to the Secretary a classification for the device and shall, if recommending classification in class II, include in the request an initial draft proposal for applicable special controls, as described in subsection (a)(1)(B), that are necessary, in conjunction with general controls, to provide reasonable assurance of safety and effectiveness and a description of how the special controls provide such assurance. Any such request shall describe the device and provide detailed information and reasons for the recommended classification.
(B)
(i) The Secretary shall by written order classify the device involved. Such classification shall be the initial classification of the device for purposes of paragraph (1) and any device classified under this paragraph shall be a predicate device for determining substantial equivalence under paragraph (1).
(ii) A device that remains in class III under this subparagraph shall be deemed to be adulterated within the meaning of section 351(f)(1)(B) of this title until approved under section 360e of this title or exempted from such approval under section 360j(g) of this title.
(C) Within 30 days after the issuance of an order classifying a device under this paragraph, the Secretary shall publish a notice in the Federal Register announcing such classification.
(3)
(A) The Secretary may initiate the reclassification of a device classified into class III under paragraph (1) of this subsection or the manufacturer or importer of a device classified under paragraph (1) may petition the Secretary (in such form and manner as he shall prescribe) for the issuance of an order classifying the device in class I or class II. Within thirty days of the filing of such a petition, the Secretary shall notify the petitioner of any deficiencies in the petition which prevent the Secretary from making a decision on the petition.
(B)
(i) Upon determining that a petition does not contain any deficiency which prevents the Secretary from making a decision on the petition, the Secretary may for good cause shown refer the petition to an appropriate panel established or authorized to be used under subsection (b). A panel to which such a petition has been referred shall not later than ninety days after the referral of the petition make a recommendation to the Secretary respecting approval or denial of the petition. Any such recommendation shall contain (I) a summary of the reasons for the recommendation, (II) a summary of the data upon which the recommendation is based, and (III) an identification of the risks to health (if any) presented by the device with respect to which the petition was filed. In the case of a petition for a device which is intended to be implanted in the human body or which is purported or represented to be for a use in supporting or sustaining human life, the panel shall recommend that the petition be denied unless the panel determines that the classification in class III of the device is not necessary to provide reasonable assurance of its safety and effectiveness. If the panel recommends that such petition be approved, it shall in its recommendation to the Secretary set forth its reasons for such recommendation.
(ii) The requirements of paragraphs (1) and (2) of subsection (c) (relating to opportunities for submission of data and views and recommendations respecting priorities and exemptions from sections 360, 360i, and 360j(f) of this title) shall apply with respect to consideration by panels of petitions submitted under subparagraph (A).
(C)
(i) Within ninety days from the date the Secretary receives the recommendation of a panel respecting a petition (but not later than 210 days after the filing of such petition) the Secretary shall by order deny or approve the petition. If the Secretary approves the petition, the Secretary shall order the classification of the device into class I or class II in accordance with the criteria prescribed by subsection (a)(1)(A) or (a)(1)(B). In the case of a petition for a device which is intended to be implanted in the human body or which is purported or represented to be for a use in supporting or sustaining human life, the Secretary shall deny the petition unless the Secretary determines that the classification in class III of the device is not necessary to provide reasonable assurance of its safety and effectiveness. An order approving such petition shall be accompanied by a full statement of the reasons of the Secretary (and supporting documentation and data) for approving the petition and an identification of the risks to health (if any) presented by the device to which such order applies.
(ii) The requirements of paragraphs (1) and (2)(A) of subsection (d) (relating to publication of recommendations, opportunity for submission of comments, and exemption from sections 360, 360i, and 360j(f) of this title) shall apply with respect to action by the Secretary on petitions submitted under subparagraph (A).
(4) If a manufacturer reports to the Secretary under section 360(k) of this title that a device is substantially equivalent to another device—
(A) which the Secretary has classified as a class III device under subsection (b),
(B) which was introduced or delivered for introduction into interstate commerce for commercial distribution before December 1, 1990, and
(C) for which no final regulation requiring premarket approval has been promulgated under section 360e(b) of this title,
the manufacturer shall certify to the Secretary that the manufacturer has conducted a reasonable search of all information known or otherwise available to the manufacturer respecting such other device and has included in the report under section 360(k) of this title a summary of and a citation to all adverse safety and effectiveness data respecting such other device and respecting the device for which the section 360(k) report is being made and which has not been submitted to the Secretary under section 360i of this title. The Secretary may require the manufacturer to submit the adverse safety and effectiveness data described in the report.
(5) The Secretary may not withhold a determination of the initial classification of a device under paragraph (1) because of a failure to comply with any provision of this chapter unrelated to a substantial equivalence decision, including a finding that the facility in which the device is manufactured is not in compliance with good manufacturing requirements as set forth in regulations of the Secretary under section 360j(f) of this title (other than a finding that there is a substantial likelihood that the failure to comply with such regulations will potentially present a serious risk to human health).
(6)
(A) Subject to the succeeding subparagraphs of this paragraph, the Secretary shall, by written order, classify an accessory under this section based on the risks of the accessory when used as intended and the level of regulatory controls necessary to provide a reasonable assurance of safety and effectiveness of the accessory, notwithstanding the classification of any other device with which such accessory is intended to be used.
(B) The classification of any accessory distinct from another device by regulation or written order issued prior to December 13, 2016, shall continue to apply unless and until the accessory is reclassified by the Secretary, notwithstanding the classification of any other device with which such accessory is intended to be used. Nothing in this paragraph shall preclude the Secretary’s authority to initiate the classification of an accessory through regulation or written order, as appropriate.
(C)
(i) In the case of a device intended to be used with an accessory, where the accessory has been included in an application for premarket approval of such device under section 360e of this title or a report under section 360(k) of this title for clearance of such device and the Secretary has not classified such accessory distinctly from another device in accordance with subparagraph (A), the person filing the application or report (as applicable) at the time such application or report is filed—(I) may include a written request for the proper classification of the accessory pursuant to subparagraph (A);(II) shall include in any such request such information as may be necessary for the Secretary to evaluate, based on the least burdensome approach, the appropriate class for the accessory under subsection (a); and(III) shall, if the request under subclause (I) is requesting classification of the accessory in class II, include in the application an initial draft proposal for special controls, if special controls would be required pursuant to subsection (a)(1)(B).
(ii) The Secretary’s response under section 360e(d) or section 360(n) of this title (as applicable) to an application or report described in clause (i) shall also contain the Secretary’s granting or denial of the request for classification of the accessory involved.
(iii) The Secretary’s evaluation of an accessory under clause (i) shall constitute an order establishing a new classification for such accessory for the specified intended use or uses of such accessory and for any accessory with the same intended use or uses as such accessory.
(D) For accessories that have been granted marketing authorization as part of a submission for another device with which the accessory involved is intended to be used, through an application for such other device under section 360e(c) of this title, a report under section 360(k) of this title, or a request for classification under paragraph (2) of this subsection, the following shall apply:
(i) Not later than the date that is one year after August 18, 2017, and at least once every 5 years thereafter, and as the Secretary otherwise determines appropriate, pursuant to this paragraph, the Secretary shall publish in the Federal Register a notice proposing a list of such accessories that the Secretary determines may be suitable for a distinct classification in class I and the proposed regulations for such classifications. In developing such list, the Secretary shall consider recommendations from sponsors of device submissions and other stakeholders for accessories to be included on such list. The notices shall provide for a period of not less than 60 calendar days for public comment. Within 180 days after the end of the comment period, the Secretary shall publish in the Federal Register a final action classifying such suitable accessories into class I.
(ii) A manufacturer or importer of an accessory that has been granted such marketing authorization may submit to the Secretary a written request for the appropriate classification of the accessory based on the risks and appropriate level of regulatory controls as described in subparagraph (A), and shall, if the request is requesting classification of the accessory in class II, include in the submission an initial draft proposal for special controls, if special controls would be required pursuant to subsection (a)(1)(B). Such request shall include such information as may be necessary for the Secretary to evaluate, based on the least burdensome approach, the appropriate class for the accessory under subsection (a). The Secretary shall provide an opportunity for a manufacturer or importer to meet with appropriate personnel of the Food and Drug Administration to discuss the appropriate classification of such accessory prior to submitting a written request under this clause for classification of the accessory.
(iii) The Secretary shall respond to a request made under clause (ii) not later than 85 calendar days after receiving such request by issuing a written order classifying the accessory or denying the request. If the Secretary does not agree with the recommendation for classification submitted by the manufacturer or importer, the response shall include a detailed description and justification for such determination. Within 30 calendar days after granting such a request, the Secretary shall publish a notice in the Federal Register announcing such response.
(E) Nothing in this paragraph may be construed as precluding a manufacturer of an accessory of a new type from using the classification process described in subsection (f)(2) to obtain classification of such accessory in accordance with the criteria and requirements set forth in that subsection.
(g) Information
(h) DefinitionsFor purposes of this section and sections 351, 360, 360d, 360e, 360f, 360i, and 360j of this title
(1) a reference to “general controls” is a reference to the controls authorized by or under sections 351, 352, 360, 360f, 360h, 360i, and 360j of this title,
(2) a reference to “class I”, “class II”, or “class III” is a reference to a class of medical devices described in subparagraph (A), (B), or (C) of subsection (a)(1), and
(3) a reference to a “panel under section 360c of this title” is a reference to a panel established or authorized to be used under this section.
(i) Substantial equivalence
(1)
(A) For purposes of determinations of substantial equivalence under subsection (f) and section 360j(l) of this title, the term “substantially equivalent” or “substantial equivalence” means, with respect to a device being compared to a predicate device, that the device has the same intended use as the predicate device and that the Secretary by order has found that the device—
(i) has the same technological characteristics as the predicate device, or
(ii)(I) has different technological characteristics and the information submitted that the device is substantially equivalent to the predicate device contains information, including appropriate clinical or scientific data if deemed necessary by the Secretary or a person accredited under section 360m of this title, that demonstrates that the device is as safe and effective as a legally marketed device, and (II) does not raise different questions of safety and effectiveness than the predicate device.
(B) For purposes of subparagraph (A), the term “different technological characteristics” means, with respect to a device being compared to a predicate device, that there is a significant change in the materials, design, energy source, or other features of the device from those of the predicate device.
(C) To facilitate reviews of reports submitted to the Secretary under section 360(k) of this title, the Secretary shall consider the extent to which reliance on postmarket controls may expedite the classification of devices under subsection (f)(1) of this section.
(D)
(i) Whenever the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations. In making such request, the Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly.
(ii) For purposes of clause (i), the term “necessary” means the minimum required information that would support a determination of substantial equivalence between a new device and a predicate device.
(iii) Nothing in this subparagraph shall alter the standard for determining substantial equivalence between a new device and a predicate device.
(E)
(i) Any determination by the Secretary of the intended use of a device shall be based upon the proposed labeling submitted in a report for the device under section 360(k) of this title. However, when determining that a device can be found substantially equivalent to a legally marketed device, the director of the organizational unit responsible for regulating devices (in this subparagraph referred to as the “Director”) may require a statement in labeling that provides appropriate information regarding a use of the device not identified in the proposed labeling if, after providing an opportunity for consultation with the person who submitted such report, the Director determines and states in writing—(I) that there is a reasonable likelihood that the device will be used for an intended use not identified in the proposed labeling for the device; and(II) that such use could cause harm.
(ii) Such determination shall—(I) be provided to the person who submitted the report within 10 days from the date of the notification of the Director’s concerns regarding the proposed labeling;(II) specify the limitations on the use of the device not included in the proposed labeling; and(III) find the device substantially equivalent if the requirements of subparagraph (A) are met and if the labeling for such device conforms to the limitations specified in subclause (II).
(iii) The responsibilities of the Director under this subparagraph may not be delegated.
(F) Not later than 270 days after November 21, 1997, the Secretary shall issue guidance specifying the general principles that the Secretary will consider in determining when a specific intended use of a device is not reasonably included within a general use of such device for purposes of a determination of substantial equivalence under subsection (f) or section 360j(l) of this title.
(2) A device may not be found to be substantially equivalent to a predicate device that has been removed from the market at the initiative of the Secretary or that has been determined to be misbranded or adulterated by a judicial order.
(3)
(A) As part of a submission under section 360(k) of this title respecting a device, the person required to file a premarket notification under such section shall provide an adequate summary of any information respecting safety and effectiveness or state that such information will be made available upon request by any person.
(B) Any summary under subparagraph (A) respecting a device shall contain detailed information regarding data concerning adverse health effects and shall be made available to the public by the Secretary within 30 days of the issuance of a determination that such device is substantially equivalent to another device.
(j) Training and oversight of least burdensome requirements
(1) The Secretary shall—
(A) ensure that each employee of the Food and Drug Administration who is involved in the review of premarket submissions, including supervisors, receives training regarding the meaning and implementation of the least burdensome requirements under subsections (a)(3)(D) and (i)(1)(D) of this section and section 360e(c)(5) of this title; and
(B) periodically assess the implementation of the least burdensome requirements, including the employee training under subparagraph (A), to ensure that the least burdensome requirements are fully and consistently applied.
(2) Not later than 18 months after December 13, 2016, the ombudsman for any organizational unit of the Food and Drug Administration responsible for the premarket review of devices shall—
(A) conduct an audit of the training described in paragraph (1)(A), including the effectiveness of such training in implementing the least burdensome requirements;
(B) include in such audit interviews of persons who are representatives of the device industry regarding their experiences in the device premarket review process, including with respect to the application of least burdensome concepts to premarket review and decisionmaking;
(C) include in such audit a list of the measurement tools the Secretary uses to assess the implementation of the least burdensome requirements, including under paragraph (1)(B) and section 360g–1(a)(3) of this title, and may also provide feedback on the effectiveness of such tools in the implementation of the least burdensome requirements;
(D) summarize the findings of such audit in a final audit report; and
(E) within 30 calendar days of completion of such final audit report, make such final audit report available—
(i) to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives; and
(ii) on the Internet website of the Food and Drug Administration.
(k) Dual submission for certain devicesFor a device authorized for emergency use under section 360bbb–3 of this title for which, in accordance with section 360bbb–3(m) of this title, the Secretary has deemed a laboratory examination or procedure associated with such device to be in the category of examinations and procedures described in section 263a(d)(3) of title 42, the sponsor of such device may, when submitting a request for classification under subsection (f)(2), submit a single submission containing—
(1) the information needed for such a request; and
(2) sufficient information to enable the Secretary to determine whether such laboratory examination or procedure satisfies the criteria to be categorized under section 263a(d)(3) of title 42.
(June 25, 1938, ch. 675, § 513, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 540; amended Pub. L. 101–629, §§ 4(a), 5(a)–(c)(1), (3), 12(a), 18(a), Nov. 28, 1990, 104 Stat. 4515, 4517, 4518, 4523, 4528; Pub. L. 102–300, § 6(e), June 16, 1992, 106 Stat. 240; Pub. L. 103–80, § 3(s), Aug. 13, 1993, 107 Stat. 778; Pub. L. 105–115, title II, §§ 205(a), (b), 206(b), (c), 207, 208, 217, Nov. 21, 1997, 111 Stat. 2336, 2337, 2339, 2340, 2350; Pub. L. 107–250, title II, § 208, Oct. 26, 2002, 116 Stat. 1613; Pub. L. 112–144, title VI, §§ 602, 607–608(a)(2)(A), July 9, 2012, 126 Stat. 1051, 1054–1056; Pub. L. 114–255, div. A, title III, §§ 3055, 3058(a), 3060(c), 3101(a)(2)(I), Dec. 13, 2016, 130 Stat. 1127, 1128, 1133, 1154; Pub. L. 115–52, title VII, § 707(a), (b), title IX, § 901(h), Aug. 18, 2017, 131 Stat. 1060, 1062, 1077; Pub. L. 117–286, § 4(a)(155), Dec. 27, 2022, 136 Stat. 4323; Pub. L. 117–328, div. FF, title III, § 3301, Dec. 29, 2022, 136 Stat. 5831.)

CITE AS: 21 USC 360c

§ 360c–1. Reporting
The Secretary of Health and Human Services shall annually post on the Internet Web site of the Food and Drug Administration—
(1) the number and type of class I and class II devices reclassified as class II or class III in the previous calendar year under section 360c(e)(1) of this title;
(2) the number and type of class II and class III devices reclassified as class I or class II in the previous calendar year under such section 360c(e)(1) of this title; and
(3) the number and type of devices reclassified in the previous calendar year under section 360e of this title.
(Pub. L. 112–144, title VI, § 608(c), July 9, 2012, 126 Stat. 1059.)

CITE AS: 21 USC 360c-1

§ 360d. Performance standards
(a) Reasonable assurance of safe and effective performance; periodic evaluation
(1) The special controls required by section 360c(a)(1)(B) of this title shall include performance standards for a class II device if the Secretary determines that a performance standard is necessary to provide reasonable assurance of the safety and effectiveness of the device. A class III device may also be considered a class II device for purposes of establishing a standard for the device under subsection (b) if the device has been reclassified as a class II device under an administrative order under section 360c(e) of this title (or a regulation promulgated under such section prior to July 9, 2012) but such order (or regulation) provides that the reclassification is not to take effect until the effective date of such a standard for the device.
(2) A performance standard established under subsection (b) for a device—
(A) shall include provisions to provide reasonable assurance of its safe and effective performance;
(B) shall, where necessary to provide reasonable assurance of its safe and effective performance, include—
(i) provisions respecting the construction, components, ingredients, and properties of the device and its compatibility with power systems and connections to such systems,
(ii) provisions for the testing (on a sample basis or, if necessary, on an individual basis) of the device or, if it is determined that no other more practicable means are available to the Secretary to assure the conformity of the device to the standard, provisions for the testing (on a sample basis or, if necessary, on an individual basis) by the Secretary or by another person at the direction of the Secretary,
(iii) provisions for the measurement of the performance characteristics of the device,
(iv) provisions requiring that the results of each or of certain of the tests of the device required to be made under clause (ii) show that the device is in conformity with the portions of the standard for which the test or tests were required, and
(v) a provision requiring that the sale and distribution of the device be restricted but only to the extent that the sale and distribution of a device may be restricted under a regulation under section 360j(e) of this title; and
(C) shall, where appropriate, require the use and prescribe the form and span of labeling for the proper installation, maintenance, operation, and use of the device.
(3) The Secretary shall provide for periodic evaluation of performance standards established under subsection (b) to determine if such standards should be changed to reflect new medical, scientific, or other technological data.
(4) In carrying out his duties under this subsection and subsection (b), the Secretary shall, to the maximum extent practicable—
(A) use personnel, facilities, and other technical support available in other Federal agencies,
(B) consult with other Federal agencies concerned with standard-setting and other nationally or internationally recognized standard-setting entities, and
(C) invite appropriate participation, through joint or other conferences, workshops, or other means, by informed persons representative of scientific, professional, industry, or consumer organizations who in his judgment can make a significant contribution.
(b) Establishment of a standard
(1)
(A) The Secretary shall publish in the Federal Register a notice of proposed rulemaking for the establishment, amendment, or revocation of any performance standard for a device.
(B) A notice of proposed rulemaking for the establishment or amendment of a performance standard for a device shall—
(i) set forth a finding with supporting justification that the performance standard is appropriate and necessary to provide reasonable assurance of the safety and effectiveness of the device,
(ii) set forth proposed findings with respect to the risk of illness or injury that the performance standard is intended to reduce or eliminate,
(iii) invite interested persons to submit to the Secretary, within 30 days of the publication of the notice, requests for changes in the classification of the device pursuant to section 360c(e) of this title based on new information relevant to the classification, and
(iv) invite interested persons to submit an existing performance standard for the device, including a draft or proposed performance standard, for consideration by the Secretary.
(C) A notice of proposed rulemaking for the revocation of a performance standard shall set forth a finding with supporting justification that the performance standard is no longer necessary to provide reasonable assurance of the safety and effectiveness of a device.
(D) The Secretary shall provide for a comment period of not less than 60 days.
(2) If, after publication of a notice in accordance with paragraph (1), the Secretary receives a request for a change in the classification of the device, the Secretary shall, within 60 days of the publication of the notice, after consultation with the appropriate panel under section 360c of this title, either deny the request or give notice of an intent to initiate such change under section 360c(e) of this title.
(3)
(A) After the expiration of the period for comment on a notice of proposed rulemaking published under paragraph (1) respecting a performance standard and after consideration of such comments and any report from an advisory committee under paragraph (5), the Secretary shall (i) promulgate a regulation establishing a performance standard and publish in the Federal Register findings on the matters referred to in paragraph (1), or (ii) publish a notice terminating the proceeding for the development of the standard together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued because the device is a banned device under section 360f of this title) initiate a proceeding under section 360c(e) of this title to reclassify the device subject to the proceeding terminated by such notice.
(B) A regulation establishing a performance standard shall set forth the date or dates upon which the standard shall take effect, but no such regulation may take effect before one year after the date of its publication unless (i) the Secretary determines that an earlier effective date is necessary for the protection of the public health and safety, or (ii) such standard has been established for a device which, effective upon the effective date of the standard, has been reclassified from class III to class II. Such date or dates shall be established so as to minimize, consistent with the public health and safety, economic loss to, and disruption or dislocation of, domestic and international trade.
(4)
(A) The Secretary, upon his own initiative or upon petition of an interested person may by regulation, promulgated in accordance with the requirements of paragraphs (1), (2), and (3)(B) of this subsection, amend or revoke a performance standard.
(B) The Secretary may declare a proposed amendment of a performance standard to be effective on and after its publication in the Federal Register and until the effective date of any final action taken on such amendment if he determines that making it so effective is in the public interest. A proposed amendment of a performance standard made so effective under the preceding sentence may not prohibit, during the period in which it is so effective, the introduction or delivery for introduction into interstate commerce of a device which conforms to such standard without the change or changes provided by such proposed amendment.
(5)
(A) The Secretary—
(i) may on his own initiative refer a proposed regulation for the establishment, amendment, or revocation of a performance standard, or
(ii) shall, upon the request of an interested person which demonstrates good cause for referral and which is made before the expiration of the period for submission of comments on such proposed regulation refer such proposed regulation,
to an advisory committee of experts, established pursuant to subparagraph (B), for a report and recommendation with respect to any matter involved in the proposed regulation which requires the exercise of scientific judgment. If a proposed regulation is referred under this subparagraph to an advisory committee, the Secretary shall provide the advisory committee with the data and information on which such proposed regulation is based. The advisory committee shall, within sixty days of the referral of a proposed regulation and after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation respecting such regulation, together with all underlying data and information and a statement of the reason or basis for the recommendation. A copy of such report and recommendation shall be made public by the Secretary.
(B) The Secretary shall establish advisory committees (which may not be panels under section 360c of this title) to receive referrals under subparagraph (A). The Secretary shall appoint as members of any such advisory committee persons qualified in the subject matter to be referred to the committee and of appropriately diversified professional background, except that the Secretary may not appoint to such a committee any individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter. Each such committee shall include as nonvoting members a representative of consumer interests and a representative of interests of the device manufacturing industry. Members of an advisory committee who are not officers or employees of the United States, while attending conferences or meetings of their committee or otherwise serving at the request of the Secretary, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate one of the members of each advisory committee to serve as chairman thereof. The Secretary shall furnish each advisory committee with clerical and other assistance, and shall by regulation prescribe the procedures to be followed by each such committee in acting on referrals made under subparagraph (A).
(c) Recognition of standard
(1)
(A) In addition to establishing a performance standard under this section, the Secretary shall, by publication in the Federal Register (or, with respect to a susceptibility test interpretive criteria standard under section 360a–2 of this title, by posting on the Interpretive Criteria Website in accordance with such section), recognize all or part of an appropriate standard established by a nationally or internationally recognized standard development organization for which a person may submit a declaration of conformity in order to meet a premarket submission requirement or other requirement under this chapter to which such standard is applicable.
(B) If a person elects to use a standard recognized by the Secretary under subparagraph (A) to meet the requirements described in such subparagraph, the person shall provide a declaration of conformity to the Secretary that certifies that the device is in conformity with such standard. A person may elect to use data, or information, other than data required by a standard recognized under subparagraph (A) to meet any requirement regarding devices under this chapter.
(C)
(i) Any person may submit a request for recognition under subparagraph (A) of all or part of an appropriate standard established by a nationally or internationally recognized standard organization.1
1 So in original. Probably should be “standard development organization.”
(ii) Not later than 60 calendar days after the Secretary receives such a request, the Secretary shall—(I) make a determination to recognize all, part, or none of the standard that is the subject of the request; and(II) issue to the person who submitted such request a response in writing that states the Secretary’s rationale for that determination, including the scientific, technical, regulatory, or other basis for such determination.
(iii) The Secretary shall make a response issued under clause (ii)(II) publicly available, in such a manner as the Secretary determines appropriate.
(iv) The Secretary shall take such actions as may be necessary to implement all or part of a standard recognized under clause (ii)(I), in accordance with subparagraph (A).
(D) The Secretary shall make publicly available, in such manner as the Secretary determines appropriate, the rationale for recognition under subparagraph (A) of all, part, or none of a standard, including the scientific, technical, regulatory, or other basis for the decision regarding such recognition.
(2) The Secretary may withdraw such recognition of a standard through publication of a notice in the Federal Register if the Secretary determines that the standard is no longer appropriate for meeting a requirement regarding devices under this chapter.
(3)
(A) Subject to subparagraph (B), the Secretary shall accept a declaration of conformity that a device is in conformity with a standard recognized under paragraph (1) unless the Secretary finds—
(i) that the data or information submitted to support such declaration does not demonstrate that the device is in conformity with the standard identified in the declaration of conformity; or
(ii) that the standard identified in the declaration of conformity is not applicable to the particular device under review.
(B) The Secretary may request, at any time, the data or information relied on by the person to make a declaration of conformity with respect to a standard recognized under paragraph (1).
(C) A person making a declaration of conformity with respect to a standard recognized under paragraph (1) shall maintain the data and information demonstrating conformity of the device to the standard for a period of two years after the date of the classification or approval of the device by the Secretary or a period equal to the expected design life of the device, whichever is longer.
(4) The Secretary shall provide to all employees of the Food and Drug Administration who review premarket submissions for devices periodic training on the concept and use of recognized standards for purposes of meeting a premarket submission requirement or other applicable requirement under this chapter, including standards relevant to an employee’s area of device review.
(d) Accreditation scheme for conformity assessment
(1) In generalThe Secretary shall establish a program under which—
(A) testing laboratories meeting criteria specified in guidance by the Secretary may be accredited, by accreditation bodies meeting criteria specified in guidance by the Secretary, to conduct testing to support the assessment of the conformity of a device to certain standards recognized under this section; and
(B) subject to paragraph (2), results from tests conducted to support the assessment of conformity of devices as described in subparagraph (A) conducted by testing laboratories accredited pursuant to this subsection shall be accepted by the Secretary for purposes of demonstrating such conformity unless the Secretary finds that certain results of such tests should not be so accepted.
(2) Secretarial review of accredited laboratory resultsThe Secretary may—
(A) review the results of tests conducted by testing laboratories accredited pursuant to this subsection, including by conducting periodic audits of such results or of the processes of accredited bodies or testing laboratories;
(B) following such review, take additional measures under this chapter, as the Secretary determines appropriate, such as—
(i) suspension or withdrawal of accreditation of a testing laboratory or recognition of an accreditation body under paragraph (1)(A); or
(ii) requesting additional information with respect to a device; and
(C) if the Secretary becomes aware of information materially bearing on the safety or effectiveness of a device for which an assessment of conformity was supported by testing conducted by a testing laboratory accredited under this subsection, take such additional measures under this chapter, as the Secretary determines appropriate, such as—
(i) suspension or withdrawal of accreditation of a testing laboratory or recognition of an accreditation body under paragraph (1)(A); or
(ii) requesting additional information with regard to such device.
(3) Report
(June 25, 1938, ch. 675, § 514, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 546; amended Pub. L. 94–460, title III, § 304, Oct. 8, 1976, 90 Stat. 1960; Pub. L. 101–629, §§ 6(a), (b)(1), 18(b), Nov. 28, 1990, 104 Stat. 4519, 4528; Pub. L. 102–300, § 6(g), June 16, 1992, 106 Stat. 241; Pub. L. 103–80, § 4(a)(1), Aug. 13, 1993, 107 Stat. 779; Pub. L. 105–115, title II, § 204(a), (d), Nov. 21, 1997, 111 Stat. 2335, 2336; Pub. L. 112–144, title VI, § 608(a)(2)(B), July 9, 2012, 126 Stat. 1056; Pub. L. 114–255, div. A, title III, §§ 3044(b)(3), 3053(a), Dec. 13, 2016, 130 Stat. 1121, 1125; Pub. L. 115–52, title II, § 205(a), Aug. 18, 2017, 131 Stat. 1016; Pub. L. 117–180, div. F, title II, § 2005, Sept. 30, 2022, 136 Stat. 2153.)

CITE AS: 21 USC 360d

§ 360e. Premarket approval
(a) General requirementA class III device—
(1) which is subject to an order issued under subsection (b) (or a regulation promulgated under such subsection prior to July 9, 2012); or
(2) which is a class III device because of section 360c(f) of this title,
is required to have, unless exempt under section 360j(g) of this title, an approval under this section of an application for premarket approval or, as applicable, an approval under subsection (c)(2) of a report seeking premarket approval.
(b) Order to require premarket approval
(1) In the case of a class III device which—
(A) was introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976; or
(B) is (i) of a type so introduced or delivered, and (ii) is substantially equivalent to another device within that type,
the Secretary shall by administrative order following publication of a proposed order in the Federal Register, a meeting of a device classification panel described in section 360c(b) of this title, and consideration of comments from all affected stakeholders, including patients, payors, and providers, notwithstanding subchapter II of chapter 5 of title 5, require that such device have an approval under this section of an application for premarket approval. Authority to issue such administrative order shall not be delegated below the Director of the Center for Devices and Radiological Health, acting in consultation with the Commissioner.
(2) A proposed order required under paragraph (1) shall contain—
(A) the proposed order;
(B) proposed findings with respect to the degree of risk of illness or injury designed to be eliminated or reduced by requiring the device to have an approved application for premarket approval and the benefit to the public from use of the device;
(C) opportunity for the submission of comments on the proposed order and the proposed findings; and
(D) opportunity to request a change in the classification of the device based on new information relevant to the classification of the device.
(3) After the expiration of the period for comment on a proposed order and proposed findings published under paragraph (2), consideration of comments submitted on such proposed order and findings, and a meeting of a device classification panel described in section 360c(b) of this title, the Secretary shall (A) issue an administrative order under paragraph (1) and publish in the Federal Register findings on the matters referred to in paragraph (2)(B), or (B) publish a notice terminating the proceeding for the issuance of the administrative order together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued because the device is a banned device under section 360f of this title) initiate a proceeding under section 360c(e) of this title to reclassify the device subject to the proceeding terminated by such notice.
(c) Application for premarket approval
(1) Any person may file with the Secretary an application for premarket approval for a class III device. Such an application for a device shall contain—
(A) full reports of all information, published or known to or which should reasonably be known to the applicant, concerning investigations which have been made to show whether or not such device is safe and effective;
(B) a full statement of the components, ingredients, and properties and of the principle or principles of operation, of such device;
(C) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and, when relevant, packing and installation of, such device;
(D) an identifying reference to any performance standard under section 360d of this title which would be applicable to any aspect of such device if it were a class II device, and either adequate information to show that such aspect of such device fully meets such performance standard or adequate information to justify any deviation from such standard;
(E) such samples of such device and of components thereof as the Secretary may reasonably require, except that where the submission of such samples is impracticable or unduly burdensome, the requirement of this subparagraph may be met by the submission of complete information concerning the location of one or more such devices readily available for examination and testing;
(F) specimens of the labeling proposed to be used for such device;
(G) the certification required under section 282(j)(5)(B) of title 42 (which shall not be considered an element of such application); and
(H) such other information relevant to the subject matter of the application as the Secretary, with the concurrence of the appropriate panel under section 360c of this title, may require.
(2)
(A) Any person may file with the Secretary a report seeking premarket approval for a class III device referred to in subsection (a) that is a reprocessed single-use device. Such a report shall contain the following:
(i) The device name, including both the trade or proprietary name and the common or usual name.
(ii) The establishment registration number of the owner or operator submitting the report.
(iii) Actions taken to comply with performance standards under section 360d of this title.
(iv) Proposed labels, labeling, and advertising sufficient to describe the device, its intended use, and directions for use.
(v) Full reports of all information, published or known to or which should be reasonably known to the applicant, concerning investigations which have been made to show whether or not the device is safe or effective.
(vi) A description of the device’s components, ingredients, and properties.
(vii) A full description of the methods used in, and the facilities and controls used for, the reprocessing and packing of the device.
(viii) Such samples of the device that the Secretary may reasonably require.
(ix) A financial certification or disclosure statement or both, as required by part 54 of title 21, Code of Federal Regulations.
(x) A statement that the applicant believes to the best of the applicant’s knowledge that all data and information submitted to the Secretary are truthful and accurate and that no material fact has been omitted in the report.
(xi) Any additional data and information, including information of the type required in paragraph (1) for an application under such paragraph, that the Secretary determines is necessary to determine whether there is reasonable assurance of safety and effectiveness for the reprocessed device.
(xii) Validation data described in section 360(o)(1)(A) of this title that demonstrates that the reasonable assurance of the safety or effectiveness of the device will remain after the maximum number of times the device is reprocessed as intended by the person submitting such report.
(B) In the case of a class III device referred to in subsection (a) that is a reprocessed single-use device:
(i) Subparagraph (A) of this paragraph applies in lieu of paragraph (1).
(ii) Subject to clause (i), the provisions of this section apply to a report under subparagraph (A) to the same extent and in the same manner as such provisions apply to an application under paragraph (1).
(iii) Each reference in other sections of this chapter to an application under this section, other than such a reference in section 379i or 379j of this title, shall be considered to be a reference to a report under subparagraph (A).
(iv) Each reference in other sections of this chapter to a device for which an application under this section has been approved, or has been denied, suspended, or withdrawn, other than such a reference in section 379i or 379j of this title, shall be considered to be a reference to a device for which a report under subparagraph (A) has been approved, or has been denied, suspended, or withdrawn, respectively.
(3) Upon receipt of an application meeting the requirements set forth in paragraph (1), the Secretary—
(A) may on the Secretary’s own initiative, or
(B) shall, upon the request of an applicant unless the Secretary finds that the information in the application which would be reviewed by a panel substantially duplicates information which has previously been reviewed by a panel appointed under section 360c of this title,
refer such application to the appropriate panel under section 360c of this title for study and for submission (within such period as he may establish) of a report and recommendation respecting approval of the application, together with all underlying data and the reasons or basis for the recommendation. Where appropriate, the Secretary shall ensure that such panel includes, or consults with, one or more pediatric experts.
(4)
(A) Prior to the submission of an application under this subsection, the Secretary shall accept and review any portion of the application that the applicant and the Secretary agree is complete, ready, and appropriate for review, except that such requirement does not apply, and the Secretary has discretion whether to accept and review such portion, during any period in which, under section 379j(g) of this title, the Secretary does not have the authority to collect fees under section 379j(a) of this title.
(B) Each portion of a submission reviewed under subparagraph (A) and found acceptable by the Secretary shall not be further reviewed after receipt of an application that satisfies the requirements of paragraph (1), unless a significant issue of safety or effectiveness provides the Secretary reason to review such accepted portion.
(C) Whenever the Secretary determines that a portion of a submission under subparagraph (A) is unacceptable, the Secretary shall, in writing, provide to the applicant a description of any deficiencies in such portion and identify the information that is required to correct these deficiencies, unless the applicant is no longer pursuing the application.
(5)
(A) In requesting additional information with respect to an application under this section, the Secretary shall consider the least burdensome appropriate means necessary to demonstrate a reasonable assurance of device safety and effectiveness.
(B) For purposes of subparagraph (A), the term “necessary” means the minimum required information that would support a determination by the Secretary that an application provides a reasonable assurance of the safety and effectiveness of the device.
(C) For purposes of this paragraph, the Secretary shall consider the role of postmarket information in determining the least burdensome means of demonstrating a reasonable assurance of device safety and effectiveness.
(D) Nothing in this paragraph alters the standards for premarket approval of a device.
(d) Action on application for premarket approval
(1)
(A) As promptly as possible, but in no event later than one hundred and eighty days after the receipt of an application under subsection (c) (except as provided in section 360j(l)(3)(D)(ii) of this title or unless, in accordance with subparagraph (B)(i), an additional period as agreed upon by the Secretary and the applicant), the Secretary, after considering the report and recommendation submitted under paragraph (2) of such subsection, shall—
(i) issue an order approving the application if he finds that none of the grounds for denying approval specified in paragraph (2) of this subsection applies; or
(ii) deny approval of the application if he finds (and sets forth the basis for such finding as part of or accompanying such denial) that one or more grounds for denial specified in paragraph (2) of this subsection apply.
In making the determination whether to approve or deny the application, the Secretary shall rely on the conditions of use included in the proposed labeling as the basis for determining whether or not there is a reasonable assurance of safety and effectiveness, if the proposed labeling is neither false nor misleading. In determining whether or not such labeling is false or misleading, the Secretary shall fairly evaluate all material facts pertinent to the proposed labeling.
(B)
(i) The Secretary may not enter into an agreement to extend the period in which to take action with respect to an application submitted for a device subject to a regulation promulgated under subsection (b) unless he finds that the continued availability of the device is necessary for the public health.
(ii) An order approving an application for a device may require as a condition to such approval that the sale and distribution of the device be restricted but only to the extent that the sale and distribution of a device may be restricted under a regulation under section 360j(e) of this title.
(iii) The Secretary shall accept and review statistically valid and reliable data and any other information from investigations conducted under the authority of regulations required by section 360j(g) of this title to make a determination of whether there is a reasonable assurance of safety and effectiveness of a device subject to a pending application under this section if—(I) the data or information is derived from investigations of an earlier version of the device, the device has been modified during or after the investigations (but prior to submission of an application under subsection (c)) and such a modification of the device does not constitute a significant change in the design or in the basic principles of operation of the device that would invalidate the data or information; or(II) the data or information relates to a device approved under this section, is available for use under this chapter, and is relevant to the design and intended use of the device for which the application is pending.
(2) The Secretary shall deny approval of an application for a device if, upon the basis of the information submitted to the Secretary as part of the application and any other information before him with respect to such device, the Secretary finds that—
(A) there is a lack of a showing of reasonable assurance that such device is safe under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(B) there is a lack of a showing of reasonable assurance that the device is effective under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(C) the methods used in, or the facilities or controls used for, the manufacture, processing, packing, or installation of such device do not conform to the requirements of section 360j(f) of this title;
(D) based on a fair evaluation of all material facts, the proposed labeling is false or misleading in any particular; or
(E) such device is not shown to conform in all respects to a performance standard in effect under section 360d of this title compliance with which is a condition to approval of the application and there is a lack of adequate information to justify the deviation from such standard.
Any denial of an application shall, insofar as the Secretary determines to be practicable, be accompanied by a statement informing the applicant of the measures required to place such application in approvable form (which measures may include further research by the applicant in accordance with one or more protocols prescribed by the Secretary).
(3)
(A)
(i) The Secretary shall, upon the written request of an applicant, meet with the applicant, not later than 100 days after the receipt of an application that has been filed as complete under subsection (c), to discuss the review status of the application.
(ii) The Secretary shall, in writing and prior to the meeting, provide to the applicant a description of any deficiencies in the application that, at that point, have been identified by the Secretary based on an interim review of the entire application and identify the information that is required to correct those deficiencies.
(iii) The Secretary shall notify the applicant promptly of—(I) any additional deficiency identified in the application, or(II) any additional information required to achieve completion of the review and final action on the application,
that was not described as a deficiency in the written description provided by the Secretary under clause (ii).
(B) The Secretary and the applicant may, by mutual consent, establish a different schedule for a meeting required under this paragraph.
(4) An applicant whose application has been denied approval may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such denial, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g), and any interested person may obtain review, in accordance with paragraph (1) or (2) of subsection (g), of an order of the Secretary approving an application.
(5)
(A)
(i) Unless the change is consistent with a predetermined change control plan approved under section 360e–4 of this title, a supplemental application shall be required for any change to a device subject to an approved application under this subsection that affects safety or effectiveness, unless such change is a modification in a manufacturing procedure or method of manufacturing and the holder of the approved application submits a written notice to the Secretary that describes in detail the change, summarizes the data or information supporting the change, and informs the Secretary that the change has been made under the requirements of section 360j(f) of this title.
(ii) The holder of an approved application who submits a notice under clause (i) with respect to a manufacturing change of a device may distribute the device 30 days after the date on which the Secretary receives the notice, unless the Secretary within such 30-day period notifies the holder that the notice is not adequate and describes such further information or action that is required for acceptance of such change. If the Secretary notifies the holder that a supplemental application is required, the Secretary shall review the supplement within 135 days after the receipt of the supplement. The time used by the Secretary to review the notice of the manufacturing change shall be deducted from the 135-day review period if the notice meets appropriate span requirements for premarket approval supplements.
(B)
(i) Subject to clause (ii), in reviewing a supplement to an approved application, for an incremental change to the design of a device that affects safety or effectiveness, the Secretary shall approve such supplement if—(I) nonclinical data demonstrate that the design modification creates the intended additional capacity, function, or performance of the device; and(II) clinical data from the approved application and any supplement to the approved application provide a reasonable assurance of safety and effectiveness for the changed device.
(ii) The Secretary may require, when necessary, additional clinical data to evaluate the design modification of the device to provide a reasonable assurance of safety and effectiveness.
(e) Withdrawal and temporary suspension of approval of application
(1) The Secretary shall, upon obtaining, where appropriate, advice on scientific matters from a panel or panels under section 360c of this title, and after due notice and opportunity for informal hearing to the holder of an approved application for a device, issue an order withdrawing approval of the application if the Secretary finds—
(A) that such device is unsafe or ineffective under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(B) on the basis of new information before him with respect to such device, evaluated together with the evidence available to him when the application was approved, that there is a lack of a showing of reasonable assurance that the device is safe or effective under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(C) that the application contained or was accompanied by an untrue statement of a material fact;
(D) that the applicant (i) has failed to establish a system for maintaining records, or has repeatedly or deliberately failed to maintain records or to make reports, required by an applicable regulation under section 360i(a) of this title, (ii) has refused to permit access to, or copying or verification of, such records as required by section 374 of this title, or (iii) has not complied with the requirements of section 360 of this title;
(E) on the basis of new information before him with respect to such device, evaluated together with the evidence before him when the application was approved, that the methods used in, or the facilities and controls used for, the manufacture, processing, packing, or installation of such device do not conform with the requirements of section 360j(f) of this title and were not brought into conformity with such requirements within a reasonable time after receipt of written notice from the Secretary of nonconformity;
(F) on the basis of new information before him, evaluated together with the evidence before him when the application was approved, that the labeling of such device, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary of such fact; or
(G) on the basis of new information before him, evaluated together with the evidence before him when the application was approved, that such device is not shown to conform in all respects to a performance standard which is in effect under section 360d of this title compliance with which was a condition to approval of the application and that there is a lack of adequate information to justify the deviation from such standard.
(2) The holder of an application subject to an order issued under paragraph (1) withdrawing approval of the application may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such withdrawal, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g).
(3) If, after providing an opportunity for an informal hearing, the Secretary determines there is reasonable probability that the continuation of distribution of a device under an approved application would cause serious, adverse health consequences or death, the Secretary shall by order temporarily suspend the approval of the application approved under this section. If the Secretary issues such an order, the Secretary shall proceed expeditiously under paragraph (1) to withdraw such application.
(f) Product development protocol
(1) In the case of a class III device which is required to have an approval of an application submitted under subsection (c), such device shall be considered as having such an approval if a notice of completion of testing conducted in accordance with a product development protocol approved under paragraph (4) has been declared completed under paragraph (6).
(2) Any person may submit to the Secretary a proposed product development protocol with respect to a device. Such a protocol shall be accompanied by data supporting it. If, within thirty days of the receipt of such a protocol, the Secretary determines that it appears to be appropriate to apply the requirements of this subsection to the device with respect to which the protocol is submitted, the Secretary—
(A) may, at the initiative of the Secretary, refer the proposed protocol to the appropriate panel under section 360c of this title for its recommendation respecting approval of the protocol; or
(B) shall so refer such protocol upon the request of the submitter, unless the Secretary finds that the proposed protocol and accompanying data which would be reviewed by such panel substantially duplicate a product development protocol and accompanying data which have previously been reviewed by such a panel.
(3) A proposed product development protocol for a device may be approved only if—
(A) the Secretary determines that it is appropriate to apply the requirements of this subsection to the device in lieu of the requirement of approval of an application submitted under subsection (c); and
(B) the Secretary determines that the proposed protocol provides—
(i) a description of the device and the changes which may be made in the device,
(ii) a description of the preclinical trials (if any) of the device and a specification of (I) the results from such trials to be required before the commencement of clinical trials of the device, and (II) any permissible variations in preclinical trials and the results therefrom,
(iii) a description of the clinical trials (if any) of the device and a specification of (I) the results from such trials to be required before the filing of a notice of completion of the requirements of the protocol, and (II) any permissible variations in such trials and the results therefrom,
(iv) a description of the methods to be used in, and the facilities and controls to be used for, the manufacture, processing, and, when relevant, packing and installation of the device,
(v) an identifying reference to any performance standard under section 360d of this title to be applicable to any aspect of such device,
(vi) if appropriate, specimens of the labeling proposed to be used for such device,
(vii) such other information relevant to the subject matter of the protocol as the Secretary, with the concurrence of the appropriate panel or panels under section 360c of this title, may require, and
(viii) a requirement for submission of progress reports and, when completed, records of the trials conducted under the protocol which records are adequate to show compliance with the protocol.
(4) The Secretary shall approve or disapprove a proposed product development protocol submitted under paragraph (2) within one hundred and twenty days of its receipt unless an additional period is agreed upon by the Secretary and the person who submitted the protocol. Approval of a protocol or denial of approval of a protocol is final agency action subject to judicial review under chapter 7 of title 5.
(5) At any time after a product development protocol for a device has been approved pursuant to paragraph (4), the person for whom the protocol was approved may submit a notice of completion—
(A) stating (i) his determination that the requirements of the protocol have been fulfilled and that, to the best of his knowledge, there is no reason bearing on safety or effectiveness why the notice of completion should not become effective, and (ii) the data and other information upon which such determination was made, and
(B) setting forth the results of the trials required by the protocol and all the information required by subsection (c)(1).
(6)
(A) The Secretary may, after providing the person who has an approved protocol an opportunity for an informal hearing and at any time prior to receipt of notice of completion of such protocol, issue a final order to revoke such protocol if he finds that—
(i) such person has failed substantially to comply with the requirements of the protocol,
(ii) the results of the trials obtained under the protocol differ so substantially from the results required by the protocol that further trials cannot be justified, or
(iii) the results of the trials conducted under the protocol or available new information do not demonstrate that the device tested under the protocol does not present an unreasonable risk to health and safety.
(B) After the receipt of a notice of completion of an approved protocol the Secretary shall, within the ninety-day period beginning on the date such notice is received, by order either declare the protocol completed or declare it not completed. An order declaring a protocol not completed may take effect only after the Secretary has provided the person who has the protocol opportunity for an informal hearing on the order. Such an order may be issued only if the Secretary finds—
(i) such person has failed substantially to comply with the requirements of the protocol,
(ii) the results of the trials obtained under the protocol differ substantially from the results required by the protocol, or
(iii) there is a lack of a showing of reasonable assurance of the safety and effectiveness of the device under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof.
(C) A final order issued under subparagraph (A) or (B) shall be in writing and shall contain the reasons to support the conclusions thereof.
(7) At any time after a notice of completion has become effective, the Secretary may issue an order (after due notice and opportunity for an informal hearing to the person for whom the notice is effective) revoking the approval of a device provided by a notice of completion which has become effective as provided in subparagraph (B) if he finds that any of the grounds listed in subparagraphs (A) through (G) of subsection (e)(1) of this section apply. Each reference in such subparagraphs to an application shall be considered for purposes of this paragraph as a reference to a protocol and the notice of completion of such protocol, and each reference to the time when an application was approved shall be considered for purposes of this paragraph as a reference to the time when a notice of completion took effect.
(8) A person who has an approved protocol subject to an order issued under paragraph (6)(A) revoking such protocol, a person who has an approved protocol with respect to which an order under paragraph (6)(B) was issued declaring that the protocol had not been completed, or a person subject to an order issued under paragraph (7) revoking the approval of a device may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such order, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g).
(g) Review
(1) Upon petition for review of—
(A) an order under subsection (d) approving or denying approval of an application or an order under subsection (e) withdrawing approval of an application, or
(B) an order under subsection (f)(6)(A) revoking an approved protocol, under subsection (f)(6)(B) declaring that an approved protocol has not been completed, or under subsection (f)(7) revoking the approval of a device,
the Secretary shall, unless he finds the petition to be without good cause or unless a petition for review of such order has been submitted under paragraph (2), hold a hearing, in accordance with section 554 of title 5, on the order. The panel or panels which considered the application, protocol, or device subject to such order shall designate a member to appear and testify at any such hearing upon request of the Secretary, the petitioner, or the officer conducting the hearing, but this requirement does not preclude any other member of the panel or panels from appearing and testifying at any such hearing. Upon completion of such hearing and after considering the record established in such hearing, the Secretary shall issue an order either affirming the order subject to the hearing or reversing such order and, as appropriate, approving or denying approval of the application, reinstating the application’s approval, approving the protocol, or placing in effect a notice of completion.
(2)
(A) Upon petition for review of—
(i) an order under subsection (d) approving or denying approval of an application or an order under subsection (e) withdrawing approval of an application, or
(ii) an order under subsection (f)(6)(A) revoking an approved protocol, under subsection (f)(6)(B) declaring that an approved protocol has not been completed, or under subsection (f)(7) revoking the approval of a device,
the Secretary shall refer the application or protocol subject to the order and the basis for the order to an advisory committee of experts established pursuant to subparagraph (B) for a report and recommendation with respect to the order. The advisory committee shall, after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation, together with all underlying data and information and a statement of the reasons or basis for the recommendation. A copy of such report shall be promptly supplied by the Secretary to any person who petitioned for such referral to the advisory committee.
(B) The Secretary shall establish advisory committees (which may not be panels under section 360c of this title) to receive referrals under subparagraph (A). The Secretary shall appoint as members of any such advisory committee persons qualified in the subject matter to be referred to the committee and of appropriately diversified professional backgrounds, except that the Secretary may not appoint to such a committee any individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter. Members of an advisory committee (other than officers or employees of the United States), while attending conferences or meetings of their committee or otherwise serving at the request of the Secretary, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent for grade GS–18 of the General Schedule for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate the chairman of an advisory committee from its members. The Secretary shall furnish each advisory committee with clerical and other assistance, and shall by regulation prescribe the procedures to be followed by each such committee in acting on referrals made under subparagraph (A).
(C) The Secretary shall make public the report and recommendation made by an advisory committee with respect to an application and shall by order, stating the reasons therefor, either affirm the order referred to the advisory committee or reverse such order and, if appropriate, approve or deny approval of the application, reinstate the application’s approval, approve the protocol, or place in effect a notice of completion.
(h) Service of orders
(i) Revision
(1) Before December 1, 1995, the Secretary shall by order require manufacturers of devices, which were introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, and which are subject to revision of classification under paragraph (2), to submit to the Secretary a summary of and citation to any information known or otherwise available to the manufacturer respecting such devices, including adverse safety or effectiveness information which has not been submitted under section 360i of this title. The Secretary may require the manufacturer to submit the adverse safety or effectiveness data for which a summary and citation were submitted, if such data are available to the manufacturer.
(2) After the issuance of an order under paragraph (1) but before the date that is 2 years after July 9, 2012, the Secretary shall issue an administrative order following publication of a proposed order in the Federal Register, a meeting of a device classification panel described in section 360c(b) of this title, and consideration of comments from all affected stakeholders, including patients, payors, and providers, notwithstanding subchapter II of chapter 5 of title 5, for each device—
(A) which the Secretary has classified as a class III device, and
(B) for which no administrative order has been issued under subsection (b) (or no regulation has been promulgated under such subsection prior to July 9, 2012),
revising the classification of the device so that the device is classified into class I or class II, unless the administrative order issued under this paragraph requires the device to remain in class III. In determining whether to revise the classification of a device or to require a device to remain in class III, the Secretary shall apply the criteria set forth in section 360c(a) of this title.
(3) The Secretary shall, as promptly as is reasonably achievable, but not later than 12 months after the effective date of the order requiring a device to remain in class III, establish a schedule for the issuance of an administrative order under subsection (b) for each device which is subject to the order requiring the device to remain in class III.
(June 25, 1938, ch. 675, § 515, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 552; amended Pub. L. 101–629, §§ 4(b)(1), 9(a), 18(c), Nov. 28, 1990, 104 Stat. 4515, 4521, 4528; Pub. L. 103–80, § 3(t), Aug. 13, 1993, 107 Stat. 778; Pub. L. 105–115, title II, §§ 201(b), 202, 205(c), 209(b), 216(b), Nov. 21, 1997, 111 Stat. 2334, 2338, 2341, 2349; Pub. L. 107–250, title II, §§ 209, 210, title III, § 302(c), Oct. 26, 2002, 116 Stat. 1613, 1614, 1618; Pub. L. 108–214, § 2(d)(1), Apr. 1, 2004, 118 Stat. 576; Pub. L. 110–85, title VIII, § 801(b)(3)(D), Sept. 27, 2007, 121 Stat. 921; Pub. L. 112–144, title II, § 203(g), title VI, § 608(b)(1), July 9, 2012, 126 Stat. 1006, 1056; Pub. L. 114–255, div. A, title III, §§ 3051(c)(1), 3058(b), 3101(a)(2)(J), Dec. 13, 2016, 130 Stat. 1124, 1129, 1154; Pub. L. 115–52, title II, § 203(f)(2)(A), Aug. 18, 2017, 131 Stat. 1015; Pub. L. 117–328, div. FF, title III, § 3308(b)(2), Dec. 29, 2022, 136 Stat. 5836.)

CITE AS: 21 USC 360e

§ 360e–1. Pediatric uses of devices
(a) New devices
(1) In general
(2) Required information
The application or protocol described in paragraph (1) shall include, with respect to the device for which approval is sought and if readily available—
(A) a description of any pediatric subpopulations that suffer from the disease or condition that the device is intended to treat, diagnose, or cure; and
(B) the number of affected pediatric patients.
(3) Annual report
Not later than 18 months after September 27, 2007, and annually thereafter, the Secretary shall submit to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives a report that includes—
(A) the number of devices approved in the year preceding the year in which the report is submitted, for which there is a pediatric subpopulation that suffers from the disease or condition that the device is intended to treat, diagnose, or cure;
(B) any information, based on a review of data available to the Secretary, regarding devices used in pediatric patients but not labeled for such use for which the Secretary determines that approved pediatric labeling could confer a benefit to pediatric patients;
(C) the number of pediatric devices that receive a humanitarian use exemption under section 360j(m) of this title;
(D) the number of devices approved in the year preceding the year in which the report is submitted, labeled for use in pediatric patients;
(E) the number of pediatric devices approved in the year preceding the year in which the report is submitted, exempted from a fee pursuant to section 379j(a)(2)(B)(v) of this title;
(F) the review time for each device described in subparagraphs (A), (C), (D), and (E);
(G) the number of devices for which the Secretary relied on data with respect to adults to support a determination of a reasonable assurance of safety and effectiveness in pediatric patients; and
(H) the number of devices for which the Secretary relied on data from one pediatric subpopulation to support a determination of a reasonable assurance of safety and effectiveness in another pediatric subpopulation.
For the items described in this paragraph, such report shall disaggregate the number of devices by pediatric subpopulation.
(b) Determination of pediatric effectiveness based on similar course of disease or condition or similar effect of device on adults
(1) In general
(2) Extrapolation between subpopulations
(c) Pediatric subpopulation
(June 25, 1938, ch. 675, § 515A, as added Pub. L. 110–85, title III, § 302, Sept. 27, 2007, 121 Stat. 859; amended Pub. L. 115–52, title V, § 502(a), Aug. 18, 2017, 131 Stat. 1037.)

CITE AS: 21 USC 360e-1

§ 360e–3. Breakthrough devices
(a) Purpose
(b) Establishment of programThe Secretary shall establish a program to expedite the development of, and provide for the priority review for, devices, as determined by the Secretary—
(1) that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions; and
(2)
(A) that represent breakthrough technologies;
(B) for which no approved or cleared alternatives exist;
(C) that offer significant advantages over existing approved or cleared alternatives, including the potential, compared to existing approved alternatives, to reduce or eliminate the need for hospitalization, improve patient quality of life, facilitate patients’ ability to manage their own care (such as through self-directed personal assistance), or establish long-term clinical efficiencies; or
(D) the availability of which is in the best interest of patients.
(c) Request for designation
(d) Designation process
(1) In general
(2) Review
(3) WithdrawalThe Secretary may not withdraw a designation granted under this section on the basis of the criteria under subsection (b) no longer applying because of the subsequent clearance or approval of another device that—
(A) was designated under this section; or
(B) was given priority review under section 360e(d)(5) of this title, as in effect prior to December 13, 2016.
(e) Expedited development and priority review
(1) ActionsFor purposes of expediting the development and review of devices designated under subsection (d) the Secretary shall—
(A) assign a team of staff, including a team leader with appropriate subject matter expertise and experience, for each device for which a request is submitted under subsection (c);
(B) provide for oversight of the team by senior agency personnel to facilitate the efficient development of the device and the efficient review of any submission described in subsection (c) for the device;
(C) adopt an efficient process for timely dispute resolution;
(D) provide for interactive and timely communication with the sponsor of the device during the development program and review process;
(E) expedite the Secretary’s review of manufacturing and quality systems compliance, as applicable;
(F) disclose to the sponsor, not less than 5 business days in advance, the topics of any consultation the Secretary intends to undertake with external experts or an advisory committee concerning the sponsor’s device and provide the sponsor the opportunity to recommend such external experts;
(G) provide for advisory committee input, as the Secretary determines appropriate (including in response to the request of the sponsor) for applications submitted under section 360e(c) of this title; and
(H) assign staff to be available within a reasonable time to address questions by institutional review committees concerning the conditions and clinical testing requirements applicable to the investigational use of the device pursuant to an exemption under section 360j(g) of this title.
(2) Additional actionsIn addition to the actions described in paragraph (1), for purposes of expediting the development and review of devices designated under subsection (d), the Secretary, in collaboration with the device sponsor, may, as appropriate—
(A) coordinate with the sponsor regarding early agreement on a data development plan;
(B) take steps to ensure that the design of clinical trials is as efficient and flexible as practicable, when scientifically appropriate;
(C) facilitate, when scientifically appropriate, expedited and efficient development and review of the device through utilization of timely postmarket data collection with regard to application for approval under section 360e(c) of this title; and
(D) agree in writing to clinical protocols that the Secretary will consider binding on the Secretary and the sponsor, subject to—
(i) changes to such protocols agreed to in writing by the sponsor and the Secretary; or
(ii) a decision, made by the director of the office responsible for reviewing the device submission, that a substantial scientific issue essential to determining the safety or effectiveness of such device exists, provided that such decision is in writing, and is made only after the Secretary provides to the device sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the substantial scientific issue.
(f) Priority review guidance
(1) ContentNot later than 1 year after December 13, 2016, the Secretary shall issue guidance on the implementation of this section. Such guidance shall—
(A) set forth the process by which a person may seek a designation under subsection (d);
(B) provide a template for requests under subsection (c);
(C) identify the criteria the Secretary will use in evaluating a request for designation under this section; and
(D) identify the criteria and processes the Secretary will use to assign a team of staff, including team leaders, to review devices designated for expedited development and priority review, including any training required for such personnel to ensure effective and efficient review.
(2) Process
(g) Rule of constructionNothing in this section shall be construed to affect—
(1) the criteria and standards for evaluating an application pursuant to section 360e(c) of this title, a report and request for classification under section 360c(f)(2) of this title, or a report under section 360(k) of this title, including the recognition of valid scientific evidence as described in section 360c(a)(3)(B) of this title and consideration and application of the least burdensome means of evaluating device effectiveness or demonstrating substantial equivalence between devices with differing technological characteristics, as applicable;
(2) the authority of the Secretary with respect to clinical holds under section 360j(g)(8)(A) of this title;
(3) the authority of the Secretary to act on an application pursuant to section 360e(d) of this title before completion of an establishment inspection, as the Secretary determines appropriate; or
(4) the authority of the Secretary with respect to postmarket surveillance under sections 360i(h) and 360l of this title.
(June 25, 1938, ch. 675, § 515B, formerly § 515C, as added Pub. L. 114–255, div. A, title III, § 3051(a), Dec. 13, 2016, 130 Stat. 1121; renumbered § 515B and amended Pub. L. 115–52, title IX, § 901(f), (g), Aug. 18, 2017, 131 Stat. 1076, 1077.)

CITE AS: 21 USC 360e-3

§ 360e–4. Predetermined change control plans for devices
(a) Approved devices
(1) In general
(2) Predetermined change control plan
(3) Scope
(b) Cleared devices
(1) In general
(2) Predetermined change control plan
The Secretary may clear a predetermined change control plan submitted in a notification submitted under section 360(k) of this title that describes planned changes that may be made to the device (and that would otherwise require a new notification), if—
(A) the device remains safe and effective without any such change; and
(B) the device would remain substantially equivalent to the predicate.
(3) Scope
(c) Predicate devices
(June 25, 1938, ch. 675, § 515C, as added Pub. L. 117–328, div. FF, title III, § 3308(a), Dec. 29, 2022, 136 Stat. 5835.)

CITE AS: 21 USC 360e-4

§ 360f. Banned devices
(a) General rule
Whenever the Secretary finds, on the basis of all available data and information, that—
(1) a device intended for human use presents substantial deception or an unreasonable and substantial risk of illness or injury for one or more intended uses; and
(2) in the case of substantial deception or an unreasonable and substantial risk of illness or injury which the Secretary determined could be corrected or eliminated by labeling or change in labeling and with respect to which the Secretary provided written notice to the manufacturer specifying the deception or risk of illness or injury, the labeling or change in labeling to correct the deception or eliminate or reduce such risk, and the period within which such labeling or change in labeling was to be done, such labeling or change in labeling was not done within such period;
he may initiate a proceeding to promulgate a regulation to make such device a banned device or to make such intended use or uses a banned intended use or uses. A device that is banned for one or more intended uses is not a legally marketed device under section 396 of this title when intended for such use or uses.
(b) Special effective date
(June 25, 1938, ch. 675, § 516, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 560; amended Pub. L. 101–629, § 18(d), Nov. 28, 1990, 104 Stat. 4529; Pub. L. 117–328, div. FF, title III, § 3306(a), Dec. 29, 2022, 136 Stat. 5834.)

CITE AS: 21 USC 360f

§ 360g. Judicial review
(a) Petition; record
Not later than thirty days after—
(1) the promulgation of a regulation under section 360c of this title classifying a device in class I, an administrative order changing the classification of a device to class I, or an order under subsection (f)(2) of such section reclassifying a device or denying a petition for reclassification of a device,
(2) the promulgation of a regulation under section 360d of this title establishing, amending, or revoking a performance standard for a device,
(3) the issuance of an order under section 360d(b)(2) or 360e(b)(2)(B) of this title denying a request for reclassification of a device,
(4) the promulgation of a regulation under paragraph (3) of section 360e(b) of this title requiring a device to have an approval of a premarket application, a regulation under paragraph (4) of that section amending or revoking a regulation under paragraph (3), or an order pursuant to section 360e(g)(1) or 360e(g)(2)(C) of this title,
(5) the promulgation of a regulation under section 360f of this title (other than a proposed regulation made effective under subsection (b) of such section upon the regulation’s publication) making a device a banned device,
(6) the issuance of an order under section 360j(f)(2) of this title,
(7) an order under section 360j(g)(4) of this title disapproving an application for an exemption of a device for investigational use or an order under section 360j(g)(5) of this title withdrawing such an exemption for a device,
(8) an order pursuant to section 360c(i) of this title, or
(9) a regulation under section 360e(i)(2) or 360j(l)(5)(B) of this title,
any person adversely affected by such regulation or order may file a petition with the United States Court of Appeals for the District of Columbia or for the circuit wherein such person resides or has his principal place of business for judicial review of such regulation or order. A copy of the petition shall be transmitted by the clerk of the court to the Secretary or other officer designated by him for that purpose. The Secretary shall file in the court the record of the proceedings on which the Secretary based his regulation or order as provided in section 2112 of title 28. For purposes of this section, the term “record” means all notices and other matter published in the Federal Register with respect to the regulation or order reviewed, all information submitted to the Secretary with respect to such regulation or order, proceedings of any panel or advisory committee with respect to such regulation or order, any hearing held with respect to such regulation or order, and any other information identified by the Secretary, in the administrative proceeding held with respect to such regulation or order, as being relevant to such regulation or order.
(b) Additional data, views, and arguments
(c) Standard for review
(d) Finality of judgments
(e) Remedies
(f) Statement of reasons
(June 25, 1938, ch. 675, § 517, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 560; amended Pub. L. 101–629, § 13, Nov. 28, 1990, 104 Stat. 4524; Pub. L. 102–300, § 6(f), June 16, 1992, 106 Stat. 240; Pub. L. 105–115, title II, § 216(a)(2), Nov. 21, 1997, 111 Stat. 2349; Pub. L. 112–144, title VI, § 608(a)(2)(C), July 9, 2012, 126 Stat. 1056.)

CITE AS: 21 USC 360g

§ 360g–1. Agency documentation and review of significant decisions regarding devices
(a) Documentation of rationale for significant decisions
(1) In general
(2) Provision of documentation
(3) Application of least burdensome requirements
(b) Review of significant decisions
(1) Request for supervisory review of significant decision
(2) Submission of request
(3) Timeframe
(A) In general
(B) Exception
(June 25, 1938, ch. 675, § 517A, as added Pub. L. 112–144, title VI, § 603, July 9, 2012, 126 Stat. 1051; amended Pub. L. 114–255, div. A, title III, §§ 3051(b), 3058(c), Dec. 13, 2016, 130 Stat. 1124, 1129;

CITE AS: 21 USC 360g-1

§ 360g–2. Third party data transparency
(a) In general
To the extent the Secretary relies on any data, analysis, or other information or findings provided by entities that has been funded in whole or in part by, or otherwise performed under contract with, the Food and Drug Administration, in regulatory decision-making with respect to devices, the Secretary shall—
(1) request access to the datasets, inputs, clinical or other assumptions, methods, analytical code, results, and other components underlying or comprising the analysis, conclusions, or other findings upon which the Secretary seeks to rely; and
(2) in the event that information described in paragraph (1) is used to support regulatory decision-making, and as otherwise appropriate, to the extent practicable, provide the manufacturer or manufacturers subject to such decision a summary of such information, subject to protection of confidential commercial information or trade secret information or personally identifiable information.
(b) Report
(c) Rule of construction
(Pub. L. 117–328, div. FF, title III, § 3307, Dec. 29, 2022, 136 Stat. 5834.)

CITE AS: 21 USC 360g-2

§ 360h. Notification and other remedies
(a) NotificationIf the Secretary determines that—
(1) a device intended for human use which is introduced or delivered for introduction into interstate commerce for commercial distribution presents an unreasonable risk of substantial harm to the public health, and
(2) notification under this subsection is necessary to eliminate the unreasonable risk of such harm and no more practicable means is available under the provisions of this chapter (other than this section) to eliminate such risk,
the Secretary may issue such order as may be necessary to assure that adequate notification is provided in an appropriate form, by the persons and means best suited under the circumstances involved, to all health professionals who prescribe or use the device and to any other person (including manufacturers, importers, distributors, retailers, and device users) who should properly receive such notification in order to eliminate such risk. An order under this subsection shall require that the individuals subject to the risk with respect to which the order is to be issued be included in the persons to be notified of the risk unless the Secretary determines that notice to such individuals would present a greater danger to the health of such individuals than no such notification. If the Secretary makes such a determination with respect to such individuals, the order shall require that the health professionals who prescribe or use the device provide for the notification of the individuals whom the health professionals treated with the device of the risk presented by the device and of any action which may be taken by or on behalf of such individuals to eliminate or reduce such risk. Before issuing an order under this subsection, the Secretary shall consult with the persons who are to give notice under the order.
(b) Repair, replacement, or refund
(1)
(A) If, after affording opportunity for an informal hearing, the Secretary determines that—
(i) a device intended for human use which is introduced or delivered for introduction into interstate commerce for commercial distribution presents an unreasonable risk of substantial harm to the public health,
(ii) there are reasonable grounds to believe that the device was not properly designed or manufactured with reference to the state of the art as it existed at the time of its design or manufacture,
(iii) there are reasonable grounds to believe that the unreasonable risk was not caused by failure of a person other than a manufacturer, importer, distributor, or retailer of the device to exercise due care in the installation, maintenance, repair, or use of the device, and
(iv) the notification authorized by subsection (a) would not by itself be sufficient to eliminate the unreasonable risk and action described in paragraph (2) of this subsection is necessary to eliminate such risk,
the Secretary may order the manufacturer, importer, or any distributor of such device, or any combination of such persons, to submit to him within a reasonable time a plan for taking one or more of the actions described in paragraph (2). An order issued under the preceding sentence which is directed to more than one person shall specify which person may decide which action shall be taken under such plan and the person specified shall be the person who the Secretary determines bears the principal, ultimate financial responsibility for action taken under the plan unless the Secretary cannot determine who bears such responsibility or the Secretary determines that the protection of the public health requires that such decision be made by a person (including a device user or health professional) other than the person he determines bears such responsibility.
(B) The Secretary shall approve a plan submitted pursuant to an order issued under subparagraph (A) unless he determines (after affording opportunity for an informal hearing) that the action or actions to be taken under the plan or the manner in which such action or actions are to be taken under the plan will not assure that the unreasonable risk with respect to which such order was issued will be eliminated. If the Secretary disapproves a plan, he shall order a revised plan to be submitted to him within a reasonable time. If the Secretary determines (after affording opportunity for an informal hearing) that the revised plan is unsatisfactory or if no revised plan or no initial plan has been submitted to the Secretary within the prescribed time, the Secretary shall (i) prescribe a plan to be carried out by the person or persons to whom the order issued under subparagraph (A) was directed, or (ii) after affording an opportunity for an informal hearing, by order prescribe a plan to be carried out by a person who is a manufacturer, importer, distributor, or retailer of the device with respect to which the order was issued but to whom the order under subparagraph (A) was not directed.
(2) The actions which may be taken under a plan submitted under an order issued under paragraph (1) are as follows:
(A) To repair the device so that it does not present the unreasonable risk of substantial harm with respect to which the order under paragraph (1) was issued.
(B) To replace the device with a like or equivalent device which is in conformity with all applicable requirements of this chapter.
(C) To refund the purchase price of the device (less a reasonable allowance for use if such device has been in the possession of the device user for one year or more—
(i) at the time of notification ordered under subsection (a), or
(ii) at the time the device user receives actual notice of the unreasonable risk with respect to which the order was issued under paragraph (1),
whichever first occurs).
(3) No charge shall be made to any person (other than a manufacturer, importer, distributor or retailer) for availing himself of any remedy, described in paragraph (2) and provided under an order issued under paragraph (1), and the person subject to the order shall reimburse each person (other than a manufacturer, importer, distributor, or retailer) who is entitled to such a remedy for any reasonable and foreseeable expenses actually incurred by such person in availing himself of such remedy.
(c) Reimbursement
(d) Effect on other liability
(e) Recall authority
(1) If the Secretary finds that there is a reasonable probability that a device intended for human use would cause serious, adverse health consequences or death, the Secretary shall issue an order requiring the appropriate person (including the manufacturers, importers, distributors, or retailers of the device)—
(A) to immediately cease distribution of such device, and
(B) to immediately notify health professionals and device user facilities of the order and to instruct such professionals and facilities to cease use of such device.
The order shall provide the person subject to the order with an opportunity for an informal hearing, to be held not later than 10 days after the date of the issuance of the order, on the actions required by the order and on whether the order should be amended to require a recall of such device. If, after providing an opportunity for such a hearing, the Secretary determines that inadequate grounds exist to support the actions required by the order, the Secretary shall vacate the order.
(2)
(A) If, after providing an opportunity for an informal hearing under paragraph (1), the Secretary determines that the order should be amended to include a recall of the device with respect to which the order was issued, the Secretary shall, except as provided in subparagraphs (B) and (C), amend the order to require a recall. The Secretary shall specify a timetable in which the device recall will occur and shall require periodic reports to the Secretary describing the progress of the recall.
(B) An amended order under subparagraph (A)—
(i) shall—(I) not include recall of a device from individuals, and(II) not include recall of a device from device user facilities if the Secretary determines that the risk of recalling such device from the facilities presents a greater health risk than the health risk of not recalling the device from use, and
(ii) shall provide for notice to individuals subject to the risks associated with the use of such device.
In providing the notice required by clause (ii), the Secretary may use the assistance of health professionals who prescribed or used such a device for individuals. If a significant number of such individuals cannot be identified, the Secretary shall notify such individuals pursuant to section 375(b) of this title.
(3) The remedy provided by this subsection shall be in addition to remedies provided by subsections (a), (b), and (c).
(June 25, 1938, ch. 675, § 518, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 562; amended Pub. L. 101–629, § 8, Nov. 28, 1990, 104 Stat. 4520; Pub. L. 102–300, § 4, June 16, 1992, 106 Stat. 239.)

CITE AS: 21 USC 360h

§ 360h–1. Program to improve the device recall system
(a) In general
The Secretary shall—
(1) establish a program to routinely and systematically assess information relating to device recalls and use such information to proactively identify strategies for mitigating health risks presented by defective or unsafe devices;
(2) clarify procedures for conducting device recall audit checks to improve the ability of investigators to perform those checks in a consistent manner;
(3) develop detailed criteria for assessing whether a person performing a device recall has performed an effective correction or action plan for the recall; and
(4) document the basis for each termination by the Food and Drug Administration of a device recall.
(b) Assessment span
The program established under subsection (a)(1) shall, at a minimum, identify—
(1) trends in the number and types of device recalls;
(2) devices that are most frequently the subject of a recall; and
(3) underlying causes of device recalls.
(c) Definition
In this section, the term “recall” means—
(1) the removal from the market of a device pursuant to an order of the Secretary under subsection (b) or (e) of section 360h of this title; or
(2) the correction or removal from the market of a device at the initiative of the manufacturer or importer of the device that is required to be reported to the Secretary under section 360i(g) of this title.
(June 25, 1938, ch. 675, § 518A, as added Pub. L. 112–144, title VI, § 605, July 9, 2012, 126 Stat. 1053; amended Pub. L. 114–255, div. A, title III, § 3101(a)(2)(K), Dec. 13, 2016, 130 Stat. 1154.)

CITE AS: 21 USC 360h-1

§ 360i. Records and reports on devices
(a) General ruleEvery person who is a manufacturer or importer of a device intended for human use shall establish and maintain such records, make such reports, and provide such information, as the Secretary may by regulation reasonably require to assure that such device is not adulterated or misbranded and to otherwise assure its safety and effectiveness. Regulations prescribed under the preceding sentence—
(1) shall require a device manufacturer or importer to report to the Secretary whenever the manufacturer or importer receives or otherwise becomes aware of information that reasonably suggests that one of its marketed devices—
(A) may have caused or contributed to a death or serious injury, or
(B) has malfunctioned and that such device or a similar device marketed by the manufacturer or importer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, which report under this subparagraph—
(i) shall be submitted in accordance with part 803 of title 21, Code of Federal Regulations (or successor regulations), unless the Secretary grants an exemption or variance from, or an alternative to, a requirement under such regulations pursuant to section 803.19 of such part, if the device involved is—(I) a class III device;(II) a class II device that is permanently implantable, is life supporting, or is life sustaining; or(III) a type of device which the Secretary has, by notice published in the Federal Register or letter to the person who is the manufacturer or importer of the device, indicated should be subject to such part 803 in order to protect the public health;
(ii) shall, if the device is not subject to clause (i), be submitted in accordance with criteria established by the Secretary for reports made pursuant to this clause, which criteria shall require the reports to be in summary form and made on a quarterly basis; or
(iii) shall, if the device is imported into the United States and for which part 803 of title 21, Code of Federal Regulations (or successor regulations) requires an importer to submit a report to the manufacturer, be submitted by the importer to the manufacturer in accordance with part 803 of title 21, Code of Federal Regulations (or successor regulations) 1
1 So in original. Probably should be followed by a semicolon.
(2) shall define the term “serious injury” to mean an injury that—
(A) is life threatening,
(B) results in permanent impairment of a body function or permanent damage to a body structure, or
(C) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure;
(3) shall require reporting of other significant adverse device experiences as determined by the Secretary to be necessary to be reported;
(4) shall not impose requirements unduly burdensome to a device manufacturer or importer taking into account his cost of complying with such requirements and the need for the protection of the public health and the implementation of this chapter;
(5) which prescribe the procedure for making requests for reports or information shall require that each request made under such regulations for submission of a report or information to the Secretary state the reason or purpose for such request and identify to the fullest extent practicable such report or information;
(6) which require submission of a report or information to the Secretary shall state the reason or purpose for the submission of such report or information and identify to the fullest extent practicable such report or information;
(7) may not require that the identity of any patient be disclosed in records, reports, or information required under this subsection unless required for the medical welfare of an individual, to determine the safety or effectiveness of a device, or to verify a record, report, or information submitted under this chapter; and
(8) may not require a manufacturer or importer of a class I device to—
(A) maintain for such a device records respecting information not in the possession of the manufacturer or importer, or
(B) to submit for such a device to the Secretary any report or information—
(i) not in the possession of the manufacturer or importer, or
(ii) on a periodic basis,
unless such report or information is necessary to determine if the device should be reclassified or if the device is adulterated or misbranded. and 2
2 So in original. The word “and” probably should not appear.
In prescribing such regulations, the Secretary shall have due regard for the professional ethics of the medical profession and the interests of patients. The prohibitions of paragraph (7) of this subsection continue to apply to rec­ords, reports, and information concerning any individual who has been a patient, irrespective of whether or when he ceases to be a patient. The Secretary shall by regulation require distributors to keep records and make such records available to the Secretary upon request. Paragraphs (4) and (8) apply to distributors to the same extent and in the same manner as such paragraphs apply to manufacturers and importers.
(b) User reports
(1)
(A) Whenever a device user facility receives or otherwise becomes aware of information that reasonably suggests that a device has or may have caused or contributed to the death of a patient of the facility, the facility shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the Secretary and, if the identity of the manufacturer is known, to the manufacturer of the device. In the case of deaths, the Secretary may by regulation prescribe a shorter period for the reporting of such information.
(B) Whenever a device user facility receives or otherwise becomes aware of—
(i) information that reasonably suggests that a device has or may have caused or contributed to the serious illness of, or serious injury to, a patient of the facility, or
(ii) other significant adverse device experiences as determined by the Secretary by regulation to be necessary to be reported,
the facility shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the manufacturer of the device or to the Secretary if the identity of the manufacturer is not known.
(C) Each device user facility shall submit to the Secretary on an annual basis a summary of the reports made under subparagraphs (A) and (B). Such summary shall be submitted on January 1 of each year. The summary shall be in such form and contain such information from such reports as the Secretary may require and shall include—
(i) sufficient information to identify the facility which made the reports for which the summary is submitted,
(ii) in the case of any product which was the subject of a report, the product name, serial number, and model number,
(iii) the name and the address of the manufacturer of such device, and
(iv) a brief description of the event reported to the manufacturer.
(D) For purposes of subparagraphs (A), (B), and (C), a device user facility shall be treated as having received or otherwise become aware of information with respect to a device of that facility when medical personnel who are employed by or otherwise formally affiliated with the facility receive or otherwise become aware of information with respect to that device in the course of their duties.
(2) The Secretary may not disclose the identity of a device user facility which makes a report under paragraph (1) except in connection with—
(A) an action brought to enforce section 331(q) of this title, or
(B) a communication to a manufacturer of a device which is the subject of a report under paragraph (1).
This paragraph does not prohibit the Secretary from disclosing the identity of a device user facility making a report under paragraph (1) or any information in such a report to employees of the Department of Health and Human Services, to the Department of Justice, or to the duly authorized committees and subcommittees of the Congress.
(3) No report made under paragraph (1) by—
(A) a device user facility,
(B) an individual who is employed by or otherwise formally affiliated with such a facility, or
(C) a physician who is not required to make such a report,
shall be admissible into evidence or otherwise used in any civil action involving private parties unless the facility, individual, or physician who made the report had knowledge of the falsity of the information contained in the report.
(4) A report made under paragraph (1) does not affect any obligation of a manufacturer who receives the report to file a report as required under subsection (a).
(5) With respect to device user facilities:
(A) The Secretary shall by regulation plan and implement a program under which the Secretary limits user reporting under paragraphs (1) through (4) to a subset of user facilities that constitutes a representative profile of user reports for device deaths and serious illnesses or serious injuries.
(B) During the period of planning the program under subparagraph (A), paragraphs (1) through (4) continue to apply.
(C) During the period in which the Secretary is providing for a transition to the full implementation of the program, paragraphs (1) through (4) apply except to the extent that the Secretary determines otherwise.
(D) On and after the date on which the program is fully implemented, paragraphs (1) through (4) do not apply to a user facility unless the facility is included in the subset referred to in subparagraph (A).
(E) Not later than 2 years after November 21, 1997, the Secretary shall submit to the Committee on Commerce of the House of Representatives, and to the Committee on Labor and Human Resources of the Senate, a report describing the plan developed by the Secretary under subparagraph (A) and the progress that has been made toward the implementation of the plan.
(6) For purposes of this subsection:
(A) The term “device user facility” means a hospital, ambulatory surgical facility, nursing home, or outpatient treatment facility which is not a physician’s office. The Secretary may by regulation include an outpatient diagnostic facility which is not a physician’s office in such term.
(B) The terms “serious illness” and “serious injury” mean illness or injury, respectively, that—
(i) is life threatening,
(ii) results in permanent impairment of a body function or permanent damage to a body structure, or
(iii) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
(c) Persons exemptSubsection (a) shall not apply to—
(1) any practitioner who is licensed by law to prescribe or administer devices intended for use in humans and who manufactures or imports devices solely for use in the course of his professional practice;
(2) any person who manufactures or imports devices intended for use in humans solely for such person’s use in research or teaching and not for sale (including any person who uses a device under an exemption granted under section 360j(g) of this title); and
(3) any other class of persons as the Secretary may by regulation exempt from subsection (a) upon a finding that compliance with the requirements of such subsection by such class with respect to a device is not necessary to (A) assure that a device is not adulterated or misbranded or (B) otherwise to assure its safety and effectiveness.
(d) Repealed. Pub. L. 105–115, title II, § 213(a)(2), Nov. 21, 1997, 111 Stat. 2347
(e) Device tracking
(1) The Secretary may by order require a manufacturer to adopt a method of tracking a class II or class III device—
(A) the failure of which would be reasonably likely to have serious adverse health consequences; or
(B) which is—
(i) intended to be implanted in the human body for more than one year, or
(ii) a life sustaining or life supporting device used outside a device user facility.
(2) Any patient receiving a device subject to tracking under paragraph (1) may refuse to release, or refuse permission to release, the patient’s name, address, social security number, or other identifying information for the purpose of tracking.
(f) Unique device identification system
(g) Reports of removals and corrections
(1) Except as provided in paragraph (2), the Secretary shall by regulation require a manufacturer or importer of a device to report promptly to the Secretary any correction or removal of a device undertaken by such manufacturer or importer if the removal or correction was undertaken—
(A) to reduce a risk to health posed by the device, or
(B) to remedy a violation of this chapter caused by the device which may present a risk to health.
A manufacturer or importer of a device who undertakes a correction or removal of a device which is not required to be reported under this paragraph shall keep a record of such correction or removal.
(2) No report of the corrective action or removal of a device may be required under paragraph (1) if a report of the corrective action or removal is required and has been submitted under subsection (a).
(3) For purposes of paragraphs (1) and (2), the terms “correction” and “removal” do not include routine servicing.
(h) Inclusion of devices in the postmarket risk identification and analysis system
(1) In general
(A) Application to devices
(B) Exception
(C) Clarification
(2) Data
(3) Stakeholder input
(4) Voluntary surveys
(i) Postmarket pilot
(1) In generalIn order to provide timely and reliable information on the safety and effectiveness of devices approved under section 360e of this title, cleared under section 360(k) of this title, or classified under section 360c(f)(2) of this title, including responses to adverse events and malfunctions, and to advance the objectives of part 803 of title 21, Code of Federal Regulations (or successor regulations), and advance the objectives of, and evaluate innovative new methods of compliance with, this section and section 360l of this title, the Secretary shall, within one year of August 18, 2017, initiate one or more pilot projects for voluntary participation by a manufacturer or manufacturers of a device or device type, or continue existing projects, in accordance with paragraph (3), that—
(A) are designed to efficiently generate reliable and timely safety and active surveillance data for use by the Secretary or manufacturers of the devices that are involved in the pilot project;
(B) inform the development of methods, systems, data criteria, and programs that could be used to support safety and active surveillance activities for devices included or not included in such project;
(C) may be designed and conducted in coordination with a comprehensive system for evaluating medical device technology that operates under a governing board with appropriate representation of stakeholders, including patient groups and device manufacturers;
(D) use electronic health data including claims data, patient survey data, or any other data, as the Secretary determines appropriate; and
(E) prioritize devices and device types that meet one or more of the following criteria:
(i) Devices and device types for which the collection and analysis of real world evidence regarding a device’s safety and effectiveness is likely to advance public health.
(ii) Devices and device types that are widely used.
(iii) Devices and device types, the failure of which has significant health consequences.
(iv) Devices and device types for which the Secretary—(I) has received public recommendations in accordance with paragraph (2)(B); and(II) has determined to meet one or more of the criteria under clause (i), (ii), or (iii) and is appropriate for such a pilot project.
(2) ParticipationThe Secretary shall establish the conditions and processes—
(A) under which a manufacturer of a device may voluntarily participate in a pilot project described in paragraph (1); and
(B) for facilitating public recommendations for devices to be prioritized under such a pilot project, including requirements for the data necessary to support such a recommendation.
(3) Continuation of ongoing projectsThe Secretary may continue or expand projects, with respect to providing timely and reliable information on the safety and effectiveness of devices approved under section 360e of this title, cleared under section 360(k) of this title, or classified under section 360c(f)(2) of this title, that are being carried out as of August 18, 2017. The Secretary shall, beginning on such date, take such steps as may be necessary—
(A) to ensure such projects meet the requirements of subparagraphs (A) through (E) of paragraph (1); and
(B) to increase the voluntary participation in such projects of manufacturers of devices and facilitate public recommendations for any devices prioritized under such a project.
(4) Implementation
(A) Contracting authorityThe Secretary may carry out a pilot project meeting the criteria specified in subparagraphs (A) through (E) of paragraph (1) or a project continued or expanded under paragraph (3) by entering into contracts, cooperative agreements, grants, or other appropriate agreements with public or private entities that have a significant presence in the United States and meet the following conditions:
(i) If such an entity is a component of another organization, the entity and the organization have established an agreement under which appropriate security measures are implemented to maintain the confidentiality and privacy of the data described in paragraph (1)(D) and such agreement ensures that the entity will not make an unauthorized disclosure of such data to the other components of the organization in breach of requirements with respect to confidentiality and privacy of such data established under such security measures.
(ii) In the case of the termination or nonrenewal of such a contract, cooperative agreement, grant, or other appropriate agreement, the entity or entities involved shall comply with each of the following:(I) The entity or entities shall continue to comply with the requirements with respect to confidentiality and privacy referred to in clause (i) with respect to all data disclosed to the entity under such an agreement.(II) The entity or entities shall return any data disclosed to such entity pursuant to this subsection and to which it would not otherwise have access or, if returning such data is not practicable, destroy the data.
(iii) The entity or entities shall have one or more qualifications with respect to—(I) research, statistical, epidemiologic, or clinical capability and expertise to conduct and complete the activities under this subsection, including the capability and expertise to provide the Secretary access to de-identified data consistent with the requirements of this subsection;(II) an information technology infrastructure to support electronic data and operational standards to provide security for such data, as appropriate;(III) experience with, and expertise on, the development of research on, and surveillance of, device safety and effectiveness using electronic health data; or(IV) such other expertise which the Secretary determines necessary to carry out such a project.
(B) Review of contract in the event of a merger or acquisition
(5) Compliance with requirements for records or reports on devicesThe participation of a manufacturer in pilot projects under this subsection or a project continued or expanded under paragraph (3) shall not affect the eligibility of such manufacturer to participate in any quarterly reporting program with respect to devices carried out under this section 360i 3
3 So in original. The section number probably should not appear.
or section 360l of this title. The Secretary may determine that, for a specified time period to be determined by the Secretary, a manufacturer’s participation in a pilot project under this subsection or a project continued or expanded under paragraph (3) may meet the applicable requirements of this section or section 360l of this title, if—
(A) the project has demonstrated success in capturing relevant adverse event information; and
(B) the Secretary has established procedures for making adverse event and safety information collected from such project public, to the extent possible.
(6) Privacy requirementsWith respect to the disclosure of any health information collected through a project conducted under this subsection—
(A) individually identifiable health information so collected shall not be disclosed when presenting any information from such project; and
(B) any such disclosure shall be made in compliance with regulations issued pursuant to section 264(c) of the Health Insurance Portability and Accountability Act of 1996 (42 U.S.C. 1320d–2 note) and sections 552 and 552a of title 5.
(7) Limitations
(8) Other projects required to comply
(9) Report to CongressNot later than 18 months after August 18, 2017, and annually thereafter, the Secretary shall submit to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor and Pensions of the Senate a report containing a description of the pilot projects being conducted under this subsection and projects continued or expanded pursuant to paragraph (3), including for each such project—
(A) how the project is being implemented in accordance with paragraph (4), including how such project is being implemented through a contract, cooperative agreement, grant, or other appropriate agreement, if applicable;
(B) the number of manufacturers that have agreed to participate in such project;
(C) the data sources used to conduct such project;
(D) the devices or device categories involved in such project;
(E) the number of patients involved in such project; and
(F) the findings of the project in relation to device safety, including adverse events, malfunctions, and other safety information.
(10) Sunset
(June 25, 1938, ch. 675, § 519, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 564; amended Pub. L. 101–629, §§ 2(a), 3(a)(1), (b)(1), 7, Nov. 28, 1990, 104 Stat. 4511, 4513, 4514, 4520; Pub. L. 102–300, § 5(a), June 16, 1992, 106 Stat. 239; Pub. L. 103–80, § 3(u), Aug. 13, 1993, 107 Stat. 778; Pub. L. 105–115, title II, §§ 211, 213(a), (c), Nov. 21, 1997, 111 Stat. 2345–2347; Pub. L. 110–85, title II, §§ 226(a), 227, Sept. 27, 2007, 121 Stat. 854; Pub. L. 112–144, title VI, §§ 614, 615, July 9, 2012, 126 Stat. 1061; Pub. L. 114–255, div. A, title III, § 3101(a)(2)(L), Dec. 13, 2016, 130 Stat. 1154; Pub. L. 115–52, title VII, § 708(a), Aug. 18, 2017, 131 Stat. 1062.)

CITE AS: 21 USC 360i

§ 360j. General provisions respecting control of devices intended for human use
(a) General rule
(b) Custom devices
(1) In generalThe requirements of sections 360d and 360e of this title shall not apply to a device that—
(A) is created or modified in order to comply with the order of an individual physician or dentist (or any other specially qualified person designated under regulations promulgated by the Secretary after an opportunity for an oral hearing);
(B) in order to comply with an order described in subparagraph (A), necessarily deviates from an otherwise applicable performance standard under section 360d of this title or requirement under section 360e of this title;
(C) is not generally available in the United States in finished form through labeling or advertising by the manufacturer, importer, or distributor for commercial distribution;
(D) is designed to treat a unique pathology or physiological condition that no other device is domestically available to treat;
(E)
(i) is intended to meet the special needs of such physician or dentist (or other specially qualified person so designated) in the course of the professional practice of such physician or dentist (or other specially qualified person so designated); or
(ii) is intended for use by an individual patient named in such order of such physician or dentist (or other specially qualified person so designated);
(F) is assembled from components or manufactured and finished on a case-by-case basis to accommodate the unique needs of individuals described in clause (i) or (ii) of subparagraph (E); and
(G) may have common, standardized design characteristics, chemical and material compositions, and manufacturing processes as commercially distributed devices.
(2) LimitationsParagraph (1) shall apply to a device only if—
(A) such device is for the purpose of treating a sufficiently rare condition, such that conducting clinical investigations on such device would be impractical;
(B) production of such device under paragraph (1) is limited to no more than 5 units per year of a particular device type, provided that such replication otherwise complies with this section; and
(C) the manufacturer of such device notifies the Secretary on an annual basis, in a manner prescribed by the Secretary, of the manufacture of such device.
(3) Guidance
(c) Trade secrets
(d) Notices and findingsEach notice of proposed rulemaking under section 360c, 360d, 360e, 360f, 360h, or 360i of this title, or under this section, any other notice which is published in the Federal Register with respect to any other action taken under any such section and which states the reasons for such action, and each publication of findings required to be made in connection with rulemaking under any such section shall set forth—
(1) the manner in which interested persons may examine data and other information on which the notice or findings is based, and
(2) the period within which interested persons may present their comments on the notice or findings (including the need therefor) orally or in writing, which period shall be at least sixty days but may not exceed ninety days unless the time is extended by the Secretary by a notice published in the Federal Register stating good cause therefor.
(e) Restricted devices
(1) The Secretary may by regulation require that a device be restricted to sale, distribution, or use—
(A) only upon the written or oral authorization of a practitioner licensed by law to administer or use such device, or
(B) upon such other conditions as the Secretary may prescribe in such regulation,
if, because of its potentiality for harmful effect or the collateral measures necessary to its use, the Secretary determines that there cannot otherwise be reasonable assurance of its safety and effectiveness. No condition prescribed under subparagraph (B) may restrict the use of a device to persons with specific training or experience in its use or to persons for use in certain facilities unless the Secretary determines that such a restriction is required for the safe and effective use of the device. No such condition may exclude a person from using a device solely because the person does not have the training or experience to make him eligible for certification by a certifying board recognized by the American Board of Medical Specialties or has not been certified by such a Board. A device subject to a regulation under this subsection is a restricted device.
(2) The label of a restricted device shall bear such appropriate statements of the restrictions required by a regulation under paragraph (1) as the Secretary may in such regulation prescribe.
(f) Good manufacturing practice requirements
(1)
(A) The Secretary may, in accordance with subparagraph (B), prescribe regulations requiring that the methods used in, and the facilities and controls used for, the manufacture, pre-production design validation (including a process to assess the performance of a device but not including an evaluation of the safety or effectiveness of a device), packing, storage, and installation of a device conform to current good manufacturing practice, as prescribed in such regulations, to assure that the device will be safe and effective and otherwise in compliance with this chapter.
(B) Before the Secretary may promulgate any regulation under subparagraph (A) he shall—
(i) afford the advisory committee established under paragraph (3) an opportunity to submit recommendations to him with respect to the regulation proposed to be promulgated;
(ii) afford opportunity for an oral hearing; and
(iii) ensure that such regulation conforms, to the extent practicable, with internationally recognized standards defining quality systems, or parts of the standards, for medical devices.
The Secretary shall provide the advisory committee a reasonable time to make its recommendation with respect to proposed regulations under subparagraph (A).
(2)
(A) Any person subject to any requirement prescribed by regulations under paragraph (1) may petition the Secretary for an exemption or variance from such requirement. Such a petition shall be submitted to the Secretary in such form and manner as he shall prescribe and shall—
(i) in the case of a petition for an exemption from a requirement, set forth the basis for the petitioner’s determination that compliance with the requirement is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter,
(ii) in the case of a petition for a variance from a requirement, set forth the methods proposed to be used in, and the facilities and controls proposed to be used for, the manufacture, packing, storage, and installation of the device in lieu of the methods, facilities, and controls prescribed by the requirement, and
(iii) contain such other information as the Secretary shall prescribe.
(B) The Secretary may refer to the advisory committee established under paragraph (3) any petition submitted under subparagraph (A). The advisory committee shall report its recommendations to the Secretary with respect to a petition referred to it within sixty days of the date of the petition’s referral. Within sixty days after—
(i) the date the petition was submitted to the Secretary under subparagraph (A), or
(ii) if the petition was referred to an advisory committee, the expiration of the sixty-day period beginning on the date the petition was referred to the advisory committee,
whichever occurs later, the Secretary shall by order either deny the petition or approve it.
(C) The Secretary may approve—
(i) a petition for an exemption for a device from a requirement if he determines that compliance with such requirement is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter, and
(ii) a petition for a variance for a device from a requirement if he determines that the methods to be used in, and the facilities and controls to be used for, the manufacture, packing, storage, and installation of the device in lieu of the methods, controls, and facilities prescribed by the requirement are sufficient to assure that the device will be safe and effective and otherwise in compliance with this chapter.
An order of the Secretary approving a petition for a variance shall prescribe such conditions respecting the methods used in, and the facilities and controls used for, the manufacture, packing, storage, and installation of the device to be granted the variance under the petition as may be necessary to assure that the device will be safe and effective and otherwise in compliance with this chapter.
(D) After the issuance of an order under subparagraph (B) respecting a petition, the petitioner shall have an opportunity for an informal hearing on such order.
(3) The Secretary shall establish an advisory committee for the purpose of advising and making recommendations to him with respect to regulations proposed to be promulgated under paragraph (1)(A) and the approval or disapproval of petitions submitted under paragraph (2). The advisory committee shall be composed of nine members as follows:
(A) Three of the members shall be appointed from persons who are officers or employees of any State or local government or of the Federal Government.
(B) Two of the members shall be appointed from persons who are representative of interests of the device manufacturing industry; two of the members shall be appointed from persons who are representative of the interests of physicians and other health professionals; and two of the members shall be representative of the interests of the general public.
Members of the advisory committee who are not officers or employees of the United States, while attending conferences or meetings of the committee or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate one of the members of the advisory committee to serve as its chairman. The Secretary shall furnish the advisory committee with clerical and other assistance. Section 1013 of title 5 shall not apply with respect to the duration of the advisory committee established under this paragraph.
(g) Exemption for devices for investigational use
(1) It is the purpose of this subsection to encourage, to the extent consistent with the protection of the public health and safety and with ethical standards, the discovery and development of useful devices intended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose.
(2)
(A) The Secretary shall, within the one hundred and twenty-day period beginning on May 28, 1976, by regulation prescribe procedures and conditions under which devices intended for human use may upon application be granted an exemption from the requirements of section 352, 360, 360d, 360e, 360f, 360i, or 379e of this title or subsection (e) or (f) of this section or from any combination of such requirements to permit the investigational use of such devices by experts qualified by scientific training and experience to investigate the safety and effectiveness of such devices.
(B) The conditions prescribed pursuant to subparagraph (A) shall include the following:
(i) A requirement that an application be submitted to the Secretary before an exemption may be granted and that the application be submitted in such form and manner as the Secretary shall specify.
(ii) A requirement that the person applying for an exemption for a device assure the establishment and maintenance of such records, and the making of such reports to the Secretary of safety or effectiveness data obtained as a result of the investigational use of the device during the exemption, as the Secretary determines will enable him to assure compliance with such conditions, review the progress of the investigation, and evaluate the safety and effectiveness of the device.
(iii) Such other requirements as the Secretary may determine to be necessary for the protection of the public health and safety.
(C) Procedures and conditions prescribed pursuant to subparagraph (A) for an exemption may appropriately vary depending on (i) the scope and duration of clinical testing to be conducted under such exemption, (ii) the number of human subjects that are to be involved in such testing, (iii) the need to permit changes to be made in the device subject to the exemption during testing conducted in accordance with a clinical testing plan required under paragraph (3)(A), and (iv) whether the clinical testing of such device is for the purpose of developing data to obtain approval for the commercial distribution of such device.
(3) Procedures and conditions prescribed pursuant to paragraph (2)(A) shall require, as a condition to the exemption of any device to be the subject of testing involving human subjects, that the person applying for the exemption—
(A) submit a plan for any proposed clinical testing of the device and a report of prior investigations of the device (including, where appropriate, tests on animals) adequate to justify the proposed clinical testing—
(i) to the institutional review committee established in accordance with regulations of the Secretary to supervise clinical testing of devices in the facilities where the proposed clinical testing is to be conducted, or
(ii) to the Secretary, if—(I) no such committee exists, or(II) the Secretary finds that the process of review by such committee is inadequate (whether or not the plan for such testing has been approved by such committee),
for review for adequacy to justify the commencement of such testing; and, unless the plan and report are submitted to the Secretary, submit to the Secretary a summary of the plan and a report of prior investigations of the device (including, where appropriate, tests on animals);
(B) promptly notify the Secretary (under such circumstances and in such manner as the Secretary prescribes) of approval by an institutional review committee of any clinical testing plan submitted to it in accordance with subparagraph (A);
(C) in the case of a device to be distributed to investigators for testing, obtain signed agreements from each of such investigators that any testing of the device involving human subjects will be under such investigator’s supervision and in accordance with subparagraph (D) and submit such agreements to the Secretary; and
(D) assure that informed consent will be obtained from each human subject (or his representative) of proposed clinical testing involving such device, except where, subject to such conditions as the Secretary may prescribe—
(i) the proposed clinical testing poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of the human subject; or
(ii) the investigator conducting or supervising the proposed clinical testing of the device determines in writing that there exists a life threatening situation involving the human subject of such testing which necessitates the use of such device and it is not feasible to obtain informed consent from the subject and there is not sufficient time to obtain such consent from his representative.
The determination required by subparagraph (D)(ii) shall be concurred in by a licensed physician who is not involved in the testing of the human subject with respect to which such determination is made unless immediate use of the device is required to save the life of the human subject of such testing and there is not sufficient time to obtain such concurrence.
(4)
(A) An application, submitted in accordance with the procedures prescribed by regulations under paragraph (2), for an exemption for a device (other than an exemption from section 360f of this title) shall be deemed approved on the thirtieth day after the submission of the application to the Secretary unless on or before such day the Secretary by order disapproves the application and notifies the applicant of the disapproval of the application.
(B) The Secretary may disapprove an application only if he finds that the investigation with respect to which the application is submitted does not conform to procedures and conditions prescribed under regulations under paragraph (2). Such a notification shall contain the order of disapproval and a complete statement of the reasons for the Secretary’s disapproval of the application and afford the applicant opportunity for an informal hearing on the disapproval order.
(C) Consistent with paragraph (1), the Secretary shall not disapprove an application under this subsection because the Secretary determines that—
(i) the investigation may not support a substantial equivalence or de novo classification determination or approval of the device;
(ii) the investigation may not meet a requirement, including a data requirement, relating to the approval or clearance of a device; or
(iii) an additional or different investigation may be necessary to support clearance or approval of the device.
(5) The Secretary may by order withdraw an exemption granted under this subsection for a device if the Secretary determines that the conditions applicable to the device under this subsection for such exemption are not met. Such an order may be issued only after opportunity for an informal hearing, except that such an order may be issued before the provision of an opportunity for an informal hearing if the Secretary determines that the continuation of testing under the exemption with respect to which the order is to be issued will result in an unreasonable risk to the public health.
(6)
(A) Not later than 1 year after November 21, 1997, the Secretary shall by regulation establish, with respect to a device for which an exemption under this subsection is in effect, procedures and conditions that, without requiring an additional approval of an application for an exemption or the approval of a supplement to such an application, permit—
(i) developmental changes in the device (including manufacturing changes) that do not constitute a significant change in design or in basic principles of operation and that are made in response to information gathered during the course of an investigation; and
(ii) changes or modifications to clinical protocols that do not affect—(I) the validity of data or information resulting from the completion of an approved protocol, or the relationship of likely patient risk to benefit relied upon to approve a protocol;(II) the scientific soundness of an investigational plan submitted under paragraph (3)(A); or(III) the rights, safety, or welfare of the human subjects involved in the investigation.
(B) Regulations under subparagraph (A) shall provide that a change or modification described in such subparagraph may be made if—
(i) the sponsor of the investigation determines, on the basis of credible information (as defined by the Secretary) that the applicable conditions under subparagraph (A) are met; and
(ii) the sponsor submits to the Secretary, not later than 5 days after making the change or modification, a notice of the change or modification.
(7)
(A) In the case of a person intending to investigate the safety or effectiveness of a class III device or any implantable device, the Secretary shall ensure that the person has an opportunity, prior to submitting an application to the Secretary or to an institutional review committee, to submit to the Secretary, for review, an investigational plan (including a clinical protocol). If the applicant submits a written request for a meeting with the Secretary regarding such review, the Secretary shall, not later than 30 days after receiving the request, meet with the applicant for the purpose of reaching agreement regarding the investigational plan (including a clinical protocol). The written request shall include a detailed description of the device, a detailed description of the proposed conditions of use of the device, a proposed plan (including a clinical protocol) for determining whether there is a reasonable assurance of effectiveness, and, if available, information regarding the expected performance from the device.
(B) Any agreement regarding the parameters of an investigational plan (including a clinical protocol) that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Any such agreement shall not be changed, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (C) by the director of the office in which the device involved is reviewed, that a substantial scientific issue essential to determining the safety or effectiveness of the device involved has been identified.
(C) A decision under subparagraph (B)(ii) by the director shall be in writing, and may be made only after the Secretary has provided to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the scientific issue involved.
(8)
(A) At any time, the Secretary may prohibit the sponsor of an investigation from conducting the investigation (referred to in this paragraph as a “clinical hold”) if the Secretary makes a determination described in subparagraph (B). The Secretary shall specify the basis for the clinical hold, including the specific information available to the Secretary which served as the basis for such clinical hold, and confirm such determination in writing.
(B) For purposes of subparagraph (A), a determination described in this subparagraph with respect to a clinical hold is a determination that—
(i) the device involved represents an unreasonable risk to the safety of the persons who are the subjects of the clinical investigation, taking into account the qualifications of the clinical investigators, information about the device, the design of the clinical investigation, the condition for which the device is to be investigated, and the health status of the subjects involved; or
(ii) the clinical hold should be issued for such other reasons as the Secretary may by regulation establish.
(C) Any written request to the Secretary from the sponsor of an investigation that a clinical hold be removed shall receive a decision, in writing and specifying the reasons therefor, within 30 days after receipt of such request. Any such request shall include sufficient information to support the removal of such clinical hold.
(9)
(A)
(i)1
1 See Delayed Applicability of Amendment note below.
The sponsor of a device for which submission of an application for an investigational device exemption is required shall submit to the Secretary in such application a diversity action plan for clinical studies of the device, in the form and manner specified in guidance issued by the Secretary.
(ii) The sponsor of a device for which submission of an application for an investigational device exemption is not required, except for a device being studied as described in section 812.2(c) of title 21, Code of Federal Regulations (or successor regulations), shall develop a diversity action plan for any clinical study with respect to the device. Such diversity action plan shall be submitted to the Secretary in any premarket notification under section 360(k) of this title, request for classification under section 360c(f)(2) of this title, or application for premarket approval under section 360e of this title for such device.
(B) A diversity action plan under clause (i) or (ii) of subparagraph (A) shall include—
(i) the sponsor’s goals for enrollment in the clinical study;
(ii) the sponsor’s rationale for such goals; and
(iii) an explanation of how the sponsor intends to meet such goals.
(C)
(i) On the initiative of the Secretary or at the request of a sponsor, the Secretary may waive any requirement in subparagraph (A) or (B) if the Secretary determines that a waiver is necessary based on what is known or can be determined about the prevalence or incidence of the disease or condition for which the device is under investigation (including in terms of the patient population that may use the device), if conducting a clinical investigation in accordance with a diversity action plan would otherwise be impracticable, or if such waiver is necessary to protect public health during a public health emergency.
(ii) The Secretary shall issue a written response granting or denying a request from a sponsor for a waiver within 60 days of receiving such request.
(D) No diversity action plan shall be required for a submission described in section 360bbb of this title.
(h) Release of information respecting safety and effectiveness
(1) The Secretary shall promulgate regulations under which a detailed summary of information respecting the safety and effectiveness of a device which information was submitted to the Secretary and which was the basis for—
(A) an order under section 360e(d)(1)(A) of this title approving an application for premarket approval for the device or denying approval of such an application or an order under section 360e(e) of this title withdrawing approval of such an application for the device,
(B) an order under section 360e(f)(6)(A) of this title revoking an approved protocol for the device, an order under section 360e(f)(6)(B) of this title declaring a protocol for the device completed or not completed, or an order under section 360e(f)(7) of this title revoking the approval of the device, or
(C) an order approving an application under subsection (g) for an exemption for the device from section 360f of this title or an order disapproving, or withdrawing approval of, an application for an exemption under such subsection for the device,
shall be made available to the public upon issuance of the order. Summaries of information made available pursuant to this paragraph respecting a device shall include information respecting any adverse effects on health of the device.
(2) The Secretary shall promulgate regulations under which each advisory committee established under section 360e(g)(2)(B) of this title shall make available to the public a detailed summary of information respecting the safety and effectiveness of a device which information was submitted to the advisory committee and which was the basis for its recommendation to the Secretary made pursuant to section 360e(g)(2)(A) of this title. A summary of information upon which such a recommendation is based shall be made available pursuant to this paragraph only after the issuance of the order with respect to which the recommendation was made and each summary shall include information respecting any adverse effect on health of the device subject to such order.
(3) Except as provided in paragraph (4), any information respecting a device which is made available pursuant to paragraph (1) or (2) of this subsection (A) may not be used to establish the safety or effectiveness of another device for purposes of this chapter by any person other than the person who submitted the information so made available, and (B) shall be made available subject to subsection (c) of this section.
(4)
(A) Subject to subparagraph (C), any information contained in an application for premarket approval filed with the Secretary pursuant to section 360e(c) of this title
(i) approving another device;
(ii) determining whether a product development protocol has been completed, under section 360e of this title for another device;
(iii) establishing a performance standard or special control under this chapter; or
(iv) classifying or reclassifying another device under section 360c of this title and subsection (l)(2).
(B) The publicly available detailed summaries of information respecting the safety and effectiveness of devices required by paragraph (1)(A) shall be available for use by the Secretary as the evidentiary basis for the agency actions described in subparagraph (A).
(C) No information contained in an application for premarket approval filed with the Secretary pursuant to section 360e(c) of this title may be used to approve or clear any application submitted under section 360e or 360(k) of this title or to classify a product under section 360c(f)(2) of this title for a combination product containing as a constituent part an approved drug (as defined in section 353(g)(5)(B) of this title) unless—
(i) the application includes the certification or statement referenced in section 353(g)(5)(A) of this title;
(ii) the applicant provides notice as described in section 353(g)(5)(A) of this title; and
(iii) the Secretary’s approval of such application is subject to the provisions in section 353(g)(5)(C) of this title.
(i) Proceedings of advisory panels and committees
(j) Traceability
(k) Research and development
(l) Transitional provisions for devices considered as new drugs
(1) Any device intended for human use—
(A) for which on May 28, 1976 (hereinafter in this subsection referred to as the “enactment date”) an approval of an application submitted under section 355(b) of this title was in effect;
(B) for which such an application was filed on or before the enactment date and with respect to which application no order of approval or refusing to approve had been issued on such date under subsection (c) or (d) of such section;
(C) for which on the enactment date an exemption under subsection (i) of such section was in effect;
(D) which is within a type of device described in subparagraph (A), (B), or (C) and is substantially equivalent to another device within that type;
(E) which the Secretary in a notice published in the Federal Register before the enactment date has declared to be a new drug subject to section 355 of this title; or
(F) with respect to which on the enactment date an action is pending in a United States court under section 332, 333, or 334 of this title for an alleged violation of a provision of section 331 of this title which enforces a requirement of section 355 of this title or for an alleged violation of section 355(a) of this title,
is classified in class III unless the Secretary in response to a petition submitted under paragraph (2) has classified such device in class I or II.
(2) The Secretary may initiate the reclassification of a device classified into class III under paragraph (1) of this subsection or the manufacturer or importer of a device classified under paragraph (1) may petition the Secretary (in such form and manner as he shall prescribe) for the issuance of an order classifying the device in class I or class II. Within thirty days of the filing of such a petition, the Secretary shall notify the petitioner of any deficiencies in the petition which prevent the Secretary from making a decision on the petition. Except as provided in paragraph (3)(D)(ii), within one hundred and eighty days after the filing of a petition under this paragraph, the Secretary shall, after consultation with the appropriate panel under section 360c of this title, by order either deny the petition or order the classification, in accordance with the criteria prescribed by section 360c(a)(1)(A) of this title or 360c(a)(1)(B) of this title, of the device in class I or class II.
(3)
(A) In the case of a device which is described in paragraph (1)(A) and which is in class III—
(i) such device shall on the enactment date be considered a device with an approved application under section 360e of this title, and
(ii) the requirements applicable to such device before the enactment date under section 355 of this title shall continue to apply to such device until changed by the Secretary as authorized by this chapter.
(B) In the case of a device which is described in paragraph (1)(B) and which is in class III, an application for such device shall be considered as having been filed under section 360e of this title on the enactment date. The period in which the Secretary shall act on such application in accordance with section 360e(d)(1) of this title shall be one hundred and eighty days from the enactment date (or such greater period as the Secretary and the applicant may agree upon after the Secretary has made the finding required by section 360e(d)(1)(B)(i) of this title) less the number of days in the period beginning on the date an application for such device was filed under section 355 of this title and ending on the enactment date. After the expiration of such period such device is required, unless exempt under subsection (g), to have in effect an approved application under section 360e of this title.
(C) A device which is described in paragraph (1)(C) and which is in class III shall be considered a new drug until the expiration of the ninety-day period beginning on the date of the promulgation of regulations under subsection (g) of this section. After the expiration of such period such device is required, unless exempt under subsection (g), to have in effect an approved application under section 360e of this title.
(D)
(i) Except as provided in clauses (ii) and (iii), a device which is described in subparagraph (D), (E), or (F) of paragraph (1) and which is in class III is required, unless exempt under subsection (g) of this section, to have on and after sixty days after the enactment date in effect an approved application under section 360e of this title.
(ii) If—(I) a petition is filed under paragraph (2) for a device described in subparagraph (D), (E), or (F) of paragraph (1), or(II) an application for premarket approval is filed under section 360e of this title for such a device,
within the sixty-day period beginning on the enactment date (or within such greater period as the Secretary, after making the finding required under section 360e(d)(1)(B) of this title, and the petitioner or applicant may agree upon), the Secretary shall act on such petition or application in accordance with paragraph (2) or section 360e of this title except that the period within which the Secretary must act on the petition or application shall be within the one hundred and twenty-day period beginning on the date the petition or application is filed. If such a petition or application is filed within such sixty-day (or greater) period, clause (i) of this subparagraph shall not apply to such device before the expiration of such one hundred and twenty-day period, or if such petition is denied or such application is denied approval, before the date of such denial, whichever occurs first.
(iii) In the case of a device which is described in subparagraph (E) of paragraph (1), which the Secretary in a notice published in the Federal Register after March 31, 1976, declared to be a new drug subject to section 355 of this title, and which is in class III—(I) the device shall, after eighteen months after the enactment date, have in effect an approved application under section 360e of this title unless exempt under subsection (g) of this section, and(II) the Secretary may, during the period beginning one hundred and eighty days after the enactment date and ending eighteen months after such date, restrict the use of the device to investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of such device, and to investigational use in accordance with the requirements applicable under regulations under subsection (g) of this section to investigational use of devices granted an exemption under such subsection.
If the requirements under subsection (g) of this section are made applicable to the investigational use of such a device, they shall be made applicable in such a manner that the device shall be made reasonably available to physicians meeting appropriate qualifications prescribed by the Secretary.
(4) Repealed. Pub. L. 105–115, title I, § 125(b)(2)(E), Nov. 21, 1997, 111 Stat. 2325.
(5)
(A) Before December 1, 1991, the Secretary shall by order require manufacturers of devices described in paragraph (1), which are subject to revision of classification under subparagraph (B), to submit to the Secretary a summary of and citation to any information known or otherwise available to the manufacturers respecting the devices, including adverse safety or effectiveness information which has not been submitted under section 360i of this title. The Secretary may require a manufacturer to submit the adverse safety or effectiveness data for which a summary and citation were submitted, if such data are available to the manufacturer.
(B) Except as provided in subparagraph (C), after the issuance of an order under subparagraph (A) but before December 1, 1992, the Secretary shall publish a regulation in the Federal Register for each device which is classified in class III under paragraph (1) revising the classification of the device so that the device is classified into class I or class II, unless the regulation requires the device to remain in class III. In determining whether to revise the classification of a device or to require a device to remain in class III, the Secretary shall apply the criteria set forth in section 360c(a) of this title. Before the publication of a regulation requiring a device to remain in class III or revising its classification, the Secretary shall publish a proposed regulation respecting the classification of a device under this subparagraph and provide an opportunity for the submission of comments on any such regulation. No regulation under this subparagraph requiring a device to remain in class III or revising its classification may take effect before the expiration of 90 days from the date of the publication in the Federal Register of the proposed regulation.
(C) The Secretary may by notice published in the Federal Register extend the period prescribed by subparagraph (B) for a device for an additional period not to exceed 1 year.
(m) Humanitarian device exemption
(1) To the extent consistent with the protection of the public health and safety and with ethical standards, it is the purpose of this subsection to encourage the discovery and use of devices intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect not more than 8,000 individuals in the United States.
(2) The Secretary may grant a request for an exemption from the effectiveness requirements of sections 360d and 360e of this title for a device for which the Secretary finds that—
(A) the device is designed to treat or diagnose a disease or condition that affects not more than 8,000 individuals in the United States,
(B) the device would not be available to a person with a disease or condition referred to in subparagraph (A) unless the Secretary grants such an exemption and there is no comparable device, other than under this exemption, available to treat or diagnose such disease or condition, and
(C) the device will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from the use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.
The request shall be in the form of an application submitted to the Secretary and such application shall include the certification required under section 282(j)(5)(B) of title 42 (which shall not be considered an element of such application). Not later than 75 days after the date of the receipt of the application, the Secretary shall issue an order approving or denying the application.
(3) Except as provided in paragraph (6), no person granted an exemption under paragraph (2) with respect to a device may sell the device for an amount that exceeds the costs of research and development, fabrication, and distribution of the device.
(4) Devices granted an exemption under paragraph (2) may only be used—
(A) in facilities in which clinical testing of devices is supervised by an institutional review committee established in accordance with the regulations of the Secretary; and
(B) if, before the use of a device, an institutional review committee or an appropriate local committee approves the use in the treatment or diagnosis of a disease or condition referred to in paragraph (2)(A), unless a physician determines in an emergency situation that approval from an institutional review committee or an appropriate local committee can not be obtained in time to prevent serious harm or death to a patient.
In a case described in subparagraph (B) in which a physician uses a device without an approval from an institutional review committee or an appropriate local committee, the physician shall, after the use of the device, notify the chairperson of the institutional review committee or an appropriate local committee of such use. Such notification shall include the identification of the patient involved, the date on which the device was used, and the reason for the use.
(5) The Secretary may require a person granted an exemption under paragraph (2) to demonstrate continued compliance with the requirements of this subsection if the Secretary believes such demonstration to be necessary to protect the public health, if the Secretary has reason to believe that the requirements of paragraph (6) are no longer met, or if the Secretary has reason to believe that the criteria for the exemption are no longer met. If the person granted an exemption under paragraph (2) fails to demonstrate continued compliance with the requirements of this subsection, the Secretary may suspend or withdraw the exemption from the effectiveness requirements of sections 360d and 360e of this title for a humanitarian device only after providing notice and an opportunity for an informal hearing.
(6)
(A) Except as provided in subparagraph (D), the prohibition in paragraph (3) shall not apply with respect to a person granted an exemption under paragraph (2) if each of the following conditions apply:
(i) The device with respect to which the exemption is granted—(I) is intended for the treatment or diagnosis of a disease or condition that occurs in pediatric patients or in a pediatric subpopulation, and such device is labeled for use in pediatric patients or in a pediatric subpopulation in which the disease or condition occurs; or(II) is intended for the treatment or diagnosis of a disease or condition that does not occur in pediatric patients or that occurs in pediatric patients in such numbers that the development of the device for such patients is impossible, highly impracticable, or unsafe.
(ii) During any calendar year, the number of such devices distributed during that year under each exemption granted under this subsection does not exceed the annual distribution number for such device. In this paragraph, the term “annual distribution number” means the number of such devices reasonably needed to treat, diagnose, or cure a population of 8,000 individuals in the United States. The Secretary shall determine the annual distribution number when the Secretary grants such exemption.
(iii) Such person immediately notifies the Secretary if the number of such devices distributed during any calendar year exceeds the annual distribution number referred to in clause (ii).
(iv) The request for such exemption is submitted on or before October 1, 2027.
(B) The Secretary may inspect the records relating to the number of devices distributed during any calendar year of a person granted an exemption under paragraph (2) for which the prohibition in paragraph (3) does not apply.
(C) A person may petition the Secretary to modify the annual distribution number determined by the Secretary under subparagraph (A)(ii) with respect to a device if additional information arises, and the Secretary may modify such annual distribution number.
(D) If a person notifies the Secretary, or the Secretary determines through an inspection under subparagraph (B), that the number of devices distributed during any calendar year exceeds the annual distribution number, as required under subparagraph (A)(iii), and modified under subparagraph (C), if applicable, then the prohibition in paragraph (3) shall apply with respect to such person for such device for any sales of such device after such notification.
(E)
(i) In this subsection, the term “pediatric patients” means patients who are 21 years of age or younger at the time of the diagnosis or treatment.
(ii) In this subsection, the term “pediatric subpopulation” means 1 of the following populations:(I) Neonates.(II) Infants.(III) Children.(IV) Adolescents.
(7) The Secretary shall refer any report of an adverse event regarding a device described in paragraph (6)(A)(i)(I) for which the prohibition under paragraph (3) does not apply pursuant to paragraph (6)(A) that the Secretary receives to the Office of Pediatric Therapeutics, established under section 393a of this title. In considering the report, the Director of the Office of Pediatric Therapeutics, in consultation with experts in the Center for Devices and Radiological Health, shall provide for periodic review of the report by the Pediatric Advisory Committee, including obtaining any recommendations of such committee regarding whether the Secretary should take action under this chapter in response to the report.
(8) The Secretary, acting through the Office of Pediatric Therapeutics and the Center for Devices and Radiological Health, shall provide for an annual review by the Pediatric Advisory Committee of all devices described in paragraph (6)(A)(i)(I) to ensure that the exemption under paragraph (2) remains appropriate for the pediatric populations for which it is granted.
(n) Regulation of contact lenses as devices
(1) All contact lenses shall be deemed to be devices under section 321(h) of this title.
(2) Paragraph (1) shall not be construed as bearing on or being relevant to the question of whether any product other than a contact lens is a device as defined by section 321(h) of this title or a drug as defined by section 321(g) of this title.
(o) Regulation of medical and certain decisions support software
(1) The term device,2
2 So in original. Probably should be “The term ‘device’,”.
as defined in section 321(h) of this title, shall not include a software function that is intended—
(A) for administrative support of a health care facility, including the processing and maintenance of financial records, claims or billing information, appointment schedules, business analytics, information about patient populations, admissions, practice and inventory management, analysis of historical claims data to predict future utilization or cost-effectiveness, determination of health benefit eligibility, population health management, and laboratory workflow;
(B) for maintaining or encouraging a healthy lifestyle and is unrelated to the diagnosis, cure, mitigation, prevention, or treatment of a disease or condition;
(C) to serve as electronic patient records, including patient-provided information, to the extent that such records are intended to transfer, store, convert formats, or display the equivalent of a paper medical chart, so long as—
(i) such records were created, stored, transferred, or reviewed by health care professionals, or by individuals working under supervision of such professionals;
(ii) such records are part of health information technology that is certified under section 300jj–11(c)(5) of title 42; and
(iii) such function is not intended to interpret or analyze patient records, including medical image data, for the purpose of the diagnosis, cure, mitigation, prevention, or treatment of a disease or condition;
(D) for transferring, storing, converting formats, or displaying clinical laboratory test or other device data and results, findings by a health care professional with respect to such data and results, general information about such findings, and general background information about such laboratory test or other device, unless such function is intended to interpret or analyze clinical laboratory test or other device data, results, and findings; or
(E) unless the function is intended to acquire, process, or analyze a medical image or a signal from an in vitro diagnostic device or a pattern or signal from a signal acquisition system, for the purpose of—
(i) displaying, analyzing, or printing medical information about a patient or other medical information (such as peer-reviewed clinical studies and clinical practice guidelines);
(ii) supporting or providing recommendations to a health care professional about prevention, diagnosis, or treatment of a disease or condition; and
(iii) enabling such health care professional to independently review the basis for such recommendations that such software presents so that it is not the intent that such health care professional rely primarily on any of such recommendations to make a clinical diagnosis or treatment decision regarding an individual patient.
(2) In the case of a product with multiple functions that contains—
(A) at least one software function that meets the criteria under paragraph (1) or that otherwise does not meet the definition of device under section 321(h) of this title; and
(B) at least one function that does not meet the criteria under paragraph (1) and that otherwise meets the definition of a device under section 321(h) of this title,
the Secretary shall not regulate the software function of such product described in subparagraph (A) as a device. Notwithstanding the preceding sentence, when assessing the safety and effectiveness of the device function or functions of such product described in subparagraph (B), the Secretary may assess the impact that the software function or functions described in subparagraph (A) have on such device function or functions.
(3)
(A) Notwithstanding paragraph (1), a software function described in subparagraph (C), (D), or (E) of paragraph (1) shall not be excluded from the definition of device under section 321(h) of this title if—
(i) the Secretary makes a finding that use of such software function would be reasonably likely to have serious adverse health consequences; and
(ii) the software function has been identified in a final order issued by the Secretary under subparagraph (B).
(B) Subparagraph (A) shall apply only if the Secretary—
(i) publishes a notification and proposed order in the Federal Register;
(ii) includes in such notification the Secretary’s finding, including the rationale and identification of the evidence on which such finding was based, as described in subparagraph (A)(i); and
(iii) provides for a period of not less than 30 calendar days for public comment before issuing a final order or withdrawing such proposed order.
(C) In making a finding under subparagraph (A)(i) with respect to a software function, the Secretary shall consider—
(i) the likelihood and severity of patient harm if the software function were to not perform as intended;
(ii) the extent to which the software function is intended to support the clinical judgment of a health care professional;
(iii) whether there is a reasonable opportunity for a health care professional to review the basis of the information or treatment recommendation provided by the software function; and
(iv) the intended user and user environment, such as whether a health care professional will use a software function of a type described in subparagraph (E) of paragraph (1).
(4) Nothing in this subsection shall be construed as limiting the authority of the Secretary to—
(A) exercise enforcement discretion as to any device subject to regulation under this chapter;
(B) regulate software used in the manufacture and transfusion of blood and blood components to assist in the prevention of disease in humans; or
(C) regulate software as a device under this chapter if such software meets the criteria under section 360c(a)(1)(C) of this title.
(p) Diagnostic imaging devices intended for use with contrast agents
(1) In generalThe Secretary may, subject to the succeeding provisions of this subsection, approve an application (or a supplement to such an application) submitted under section 360e of this title with respect to an applicable medical imaging device, or, in the case of an applicable medical imaging device for which a notification is submitted under section 360(k) of this title, may make a substantial equivalence determination with respect to an applicable medical imaging device, or may grant a request submitted under section 360c(f)(2) of this title for an applicable medical imaging device, if such application, notification, or request involves the use of a contrast agent that is not—
(A) in a concentration, rate of administration, or route of administration that is different from those described in the approved labeling of the contrast agent, except that the Secretary may approve such application, make such substantial equivalence determination, or grant such request if the Secretary determines that such differences in concentration, rate of administration, or route of administration exist but do not adversely affect the safety and effectiveness of the contrast agent when used with the device;
(B) in a region, organ, or system of the body that is different from those described in the approved labeling of the contrast agent, except that the Secretary may approve such application, make such substantial equivalence determination, or grant such request if the Secretary determines that such differences in region, organ, or system of the body exist but do not adversely affect the safety and effectiveness of the contrast agent when used with the device;
(C) in a patient population that is different from those described in the approved labeling of the contrast agent, except that the Secretary may approve such application, make such substantial equivalence determination, or grant such request if the Secretary determines such differences in patient population exist but do not adversely affect the safety and effectiveness of the contrast agent when used with the device; or
(D) in an imaging modality that is different from those described in the approved labeling of the contrast agent.
(2) Premarket reviewThe agency center charged with premarket review of devices shall have primary jurisdiction with respect to the review of an application, notification, or request described in paragraph (1). In conducting such review, such agency center may—
(A) consult with the agency center charged with the premarket review of drugs or biological products; and
(B) review information and data provided to the Secretary by the sponsor of a contrast agent in an application submitted under section 355 of this title or section 262 of title 42, so long as the sponsor of such contrast agent has provided to the sponsor of the applicable medical imaging device that is the subject of such review a right of reference and the application is submitted in accordance with this subsection.
(3) Applicable requirements
(4) DefinitionsFor purposes of this subsection—
(A) the term “applicable medical imaging device” means a device intended to be used in conjunction with a contrast agent (or class of contrast agents) for an imaging use that is not described in the approved labeling of such contrast agent (or the approved labeling of any contrast agent in the same class as such contrast agent); and
(B) the term “contrast agent” means a drug that is approved under section 355 of this title or licensed under section 262 of title 42, is intended for use in conjunction with an applicable medical imaging device, and—
(i) is a diagnostic radiopharmaceutical, as defined in section 3
3 So in original. Probably should be “sections”.
315.2 and 601.31 of title 21, Code of Federal Regulations (or any successor regulations); or
(ii) is a diagnostic agent that improves the visualization of structure or function within the body by increasing the relative difference in signal intensity within the target tissue, structure, or fluid.
(q) Regulation of over-the-counter hearing aids
(1) Definition
(A) In generalIn this subsection, the term “over-the-counter hearing aid” means a device that—
(i) uses the same fundamental scientific technology as air conduction hearing aids (as defined in section 874.3300 of title 21, Code of Federal Regulations) (or any successor regulation) or wireless air conduction hearing aids (as defined in section 874.3305 of title 21, Code of Federal Regulations) (or any successor regulation);
(ii) is intended to be used by adults age 18 and older to compensate for perceived mild to moderate hearing impairment;
(iii) through tools, tests, or software, allows the user to control the over-the-counter hearing aid and customize it to the user’s hearing needs;
(iv) may—(I) use wireless technology; or(II) include tests for self-assessment of hearing loss; and
(v) is available over-the-counter, without the supervision, prescription, or other order, involvement, or intervention of a licensed person, to consumers through in-person transactions, by mail, or online.
(B) Exception
(2) Regulation
(June 25, 1938, ch. 675, § 520, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 565; amended Pub. L. 101–629, §§ 3(b)(2), 4(b)(2), 5(c)(2), 6(b)(2), 11, 14(a), 18(e), (f), Nov. 28, 1990, 104 Stat. 4514, 4516, 4518, 4519, 4522, 4524, 4529; Pub. L. 102–571, title I, § 107(10), Oct. 29, 1992, 106 Stat. 4499; Pub. L. 105–115, title I, § 125(b)(2)(E), title II, §§ 201(a), 203, 216(a)(1), title IV, § 410(a), Nov. 21, 1997, 111 Stat. 2325, 2332, 2334, 2349, 2372; Pub. L. 109–96, § 1, Nov. 9, 2005, 119 Stat. 2119; Pub. L. 110–85, title III, § 303(a), title VIII, § 801(b)(3)(E), Sept. 27, 2007, 121 Stat. 860, 921; Pub. L. 112–144, title V, § 507(c), title VI, §§ 601, 606, 613(a), 617, July 9, 2012, 126 Stat. 1045, 1051, 1054, 1060, 1062; Pub. L. 114–255, div. A, title III, §§ 3024(a), 3038(b), 3052(a), 3056, 3060(a), Dec. 13, 2016, 130 Stat. 1099, 1110, 1124, 1128, 1130; Pub. L. 115–52, title V, § 502(b), title VII, §§ 706(a), 709(a), Aug. 18, 2017, 131 Stat. 1037, 1058, 1065; Pub. L. 117–180, div. F, title V, § 5002, Sept. 30, 2022, 136 Stat. 2167; Pub. L. 117–229, div. C, title III, § 303, Dec. 16, 2022, 136 Stat. 2312; Pub. L. 117–286, § 4(a)(156), Dec. 27, 2022, 136 Stat. 4323; Pub. L. 117–328, div. FF, title III, §§ 3103, 3601(b), Dec. 29, 2022, 136 Stat. 5807, 5861.)

CITE AS: 21 USC 360j

§ 360k. State and local requirements respecting devices
(a) General ruleExcept as provided in subsection (b), no State or political subdivision of a State may establish or continue in effect with respect to a device intended for human use any requirement—
(1) which is different from, or in addition to, any requirement applicable under this chapter to the device, and
(2) which relates to the safety or effectiveness of the device or to any other matter included in a requirement applicable to the device under this chapter.
(b) Exempt requirementsUpon application of a State or a political subdivision thereof, the Secretary may, by regulation promulgated after notice and opportunity for an oral hearing, exempt from subsection (a), under such conditions as may be prescribed in such regulation, a requirement of such State or political subdivision applicable to a device intended for human use if—
(1) the requirement is more stringent than a requirement under this chapter which would be applicable to the device if an exemption were not in effect under this subsection; or
(2) the requirement—
(A) is required by compelling local conditions, and
(B) compliance with the requirement would not cause the device to be in violation of any applicable requirement under this chapter.
(June 25, 1938, ch. 675, § 521, as added Pub. L. 94–295, § 2, May 28, 1976, 90 Stat. 574.)

CITE AS: 21 USC 360k

§ 360l. Postmarket surveillance
(a) Postmarket surveillance
(1) In general
(A) ConductThe Secretary may by order, at the time of approval or clearance of a device or at any time thereafter, require a manufacturer to conduct postmarket surveillance for any device of the manufacturer that is a class II or class III device—
(i) the failure of which would be reasonably likely to have serious adverse health consequences;
(ii) that is expected to have significant use in pediatric populations; or
(iii) that is intended to be—(I) implanted in the human body for more than 1 year; or(II) a life-sustaining or life-supporting device used outside a device user facility.
(B) Condition
(2) Rule of construction
(b) Surveillance approval
(1) In general
(2) Longer surveillance for pediatric devices
(c) Dispute resolution
(June 25, 1938, ch. 675, § 522, as added Pub. L. 101–629, § 10, Nov. 28, 1990, 104 Stat. 4521; amended Pub. L. 102–300, § 3(b), June 16, 1992, 106 Stat. 239; Pub. L. 105–115, title II, § 212, Nov. 21, 1997, 111 Stat. 2346; Pub. L. 110–85, title III, § 307, Sept. 27, 2007, 121 Stat. 865; Pub. L. 112–144, title VI, § 616, July 9, 2012, 126 Stat. 1062.)

CITE AS: 21 USC 360l

§ 360m. Accredited persons
(a) In general
(1) Review and classification of devices
(2) Requirements regarding review
(A) In general
(B) Time period for review
(C) Special rule
(3) Certain devices
(A) In generalAn accredited person may not be used to perform a review of—
(i) a class III device;
(ii) a device classified under section 360c(f)(2) of this title or designated under section 360e–3(d) 1
1 See References in Text note below.
of this title;
(iii) a device that is intended to be permanently implantable, life sustaining, or life supporting, unless otherwise determined by the Secretary in accordance with subparagraph (B)(i)(II) and listed as eligible for review under subparagraph (B)(iii); or
(iv) a device that is of a type, or subset of a type, listed as not eligible for review under subparagraph (B)(iii).
(B) Designation for reviewThe Secretary shall—
(i) issue draft guidance on the factors the Secretary will use in determining whether a class I or class II device type, or subset of such device types, is eligible for review by an accredited person, including—(I) the risk of the device type, or subset of such device type; and(II) whether the device type, or subset of such device type, is permanently implantable, life sustaining, or life supporting, and whether there is a detailed public health justification for permitting the review by an accredited person of such device type or subset;
(ii) not later than 24 months after the date on which the Secretary issues such draft guidance, finalize such guidance; and
(iii) beginning on the date such guidance is finalized, designate and post on the internet website of the Food and Drug Administration, an updated list of class I and class II device types, or subsets of such device types, and the Secretary’s determination with respect to whether each such device type, or subset of a device type, is eligible or not eligible for review by an accredited person under this section based on the factors described in clause (i).
(C) Interim rule
(b) Accreditation
(1) Programs
(2) Accreditation
(A) In general
(B) Withdrawal of accreditation
(C) Performance auditingTo ensure that persons accredited under this section will continue to meet the standards of accreditation, the Secretary shall—
(i) make onsite visits on a periodic basis to each accredited person to audit the performance of such person; and
(ii) take such additional measures as the Secretary determines to be appropriate.
(D) Periodic reaccreditation
(i) Period
(ii) Response to reaccreditation request
(iii) Criteria
(3) QualificationsAn accredited person shall, at a minimum, meet the following requirements:
(A) Such person may not be an employee of the Federal Government.
(B) Such person shall be an independent organization which is not owned or controlled by a manufacturer, supplier, or vendor of devices and which has no organizational, material, or financial affiliation with such a manufacturer, supplier, or vendor.
(C) Such person shall be a legally constituted entity permitted to conduct the activities for which it seeks accreditation.
(D) Such person shall not engage in the design, manufacture, promotion, or sale of devices.
(E) The operations of such person shall be in accordance with generally accepted professional and ethical business practices.
(F) Such person shall agree, at a minimum, to include in its request for accreditation a commitment to, at the time of accreditation, and at any time it is performing any review pursuant to this section—
(i) certify that reported information accurately reflects data reviewed;
(ii) limit work to that for which competence and capacity are available;
(iii) treat information received, records, reports, and recommendations as proprietary information;
(iv) promptly respond and attempt to resolve complaints regarding its activities for which it is accredited; and
(v) protect against the use, in carrying out subsection (a) with respect to a device, of any officer or employee of the person who has a financial conflict of interest regarding the device, and annually make available to the public disclosures of the extent to which the person, and the officers and employees of the person, have maintained compliance with requirements under this clause relating to financial conflicts of interest.
(4) Selection of accredited persons
(5) Compensation of accredited persons
(c) Duration
(June 25, 1938, ch. 675, § 523, as added Pub. L. 105–115, title II, § 210(a), Nov. 21, 1997, 111 Stat. 2342; amended Pub. L. 107–250, title II, § 202, Oct. 26, 2002, 116 Stat. 1609; Pub. L. 110–85, title II, § 221, Sept. 27, 2007, 121 Stat. 852; Pub. L. 111–31, div. A, title I, § 103(f), June 22, 2009, 123 Stat. 1837; Pub. L. 112–144, title VI, § 611, July 9, 2012, 126 Stat. 1059; Pub. L. 114–255, div. A, title III, § 3102(4), Dec. 13, 2016, 130 Stat. 1156; Pub. L. 115–52, title II, § 206, Aug. 18, 2017, 131 Stat. 1018; Pub. L. 117–180, div. F, title II, § 2006, Sept. 30, 2022, 136 Stat. 2154; Pub. L. 117–229, div. C, title III, § 309, Dec. 16, 2022, 136 Stat. 2312; Pub. L. 117–328, div. FF, title III, § 3109, Dec. 29, 2022, 136 Stat. 5808.)

CITE AS: 21 USC 360m

§ 360n. Priority review to encourage treatments for tropical diseases
(a) DefinitionsIn this section:
(1) Priority review
(2) Priority review voucher
(3) Tropical diseaseThe term “tropical disease” means any of the following:
(A) Tuberculosis.
(B) Malaria.
(C) Blinding trachoma.
(D) Buruli Ulcer.
(E) Cholera.
(F) Dengue/dengue haemorrhagic fever.
(G) Dracunculiasis (guinea-worm disease).
(H) Fascioliasis.
(I) Human African trypanosomiasis.
(J) Leishmaniasis.
(K) Leprosy.
(L) Lymphatic filariasis.
(M) Onchocerciasis.
(N) Schistosomiasis.
(O) Soil transmitted helmithiasis.
(P) Yaws.
(Q) Filovirus Diseases.
(R) Zika Virus Disease.
(S) Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations, designated by order of the Secretary.
(4) Tropical disease product applicationThe term “tropical disease product application” means an application that—
(A) is a human drug application as defined in section 379g(1) of this title—
(i) for prevention or treatment of a tropical disease;
(ii) the Secretary deems eligible for priority review;
(iii) that contains reports of one or more new clinical investigations (other than bioavailability studies) that are essential to the approval of the application and conducted or sponsored by the sponsor of such application; and
(iv) that contains an attestation from the sponsor of the application that such reports were not submitted as part of an application for marketing approval or licensure by a regulatory authority in India, Brazil, Thailand, or any country that is a member of the Pharmaceutical Inspection Convention or the Pharmaceutical Inspection Cooperation Scheme prior to September 27, 2007.1
1 So in original. The period probably should be a semicolon.
(B) is approved after September 27, 2007, by the Secretary for use in the prevention, detection, or treatment of a tropical disease; and
(C) is for—
(i) a human drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under section 355(b)(1) of this title; or
(ii) a biological product, no active ingredient of which has been approved in any other application under section 262 of title 42.
(b) Priority review voucher
(1) In general
(2) Transferability
(3) Limitation
(A) No award for prior approved application
(B) One-year waiting period
(4) Notification
(c) Priority review user fee
(1) In general
(2) Fee amount
(3) Annual fee setting
(4) Payment
(A) In general
(B) Complete application
(C) No waivers, exemptions, reductions, or refunds
(5) Offsetting collectionsFees collected pursuant to this subsection for any fiscal year—
(A) shall be deposited and credited as offsetting collections to the account providing appropriations to the Food and Drug Administration; and
(B) shall not be collected for any fiscal year except to the extent provided in advance in appropriation Acts.
(June 25, 1938, ch. 675, § 524, as added Pub. L. 110–85, title XI, § 1102, Sept. 27, 2007, 121 Stat. 972; amended Pub. L. 113–233, § 2, Dec. 16, 2014, 128 Stat. 2127; Pub. L. 114–146, § 2, Apr. 19, 2016, 130 Stat. 357; Pub. L. 114–255, div. A, title III, § 3101(a)(2)(M), Dec. 13, 2016, 130 Stat. 1154; Pub. L. 115–52, title VI, § 611(a), Aug. 18, 2017, 131 Stat. 1054; Pub. L. 117–9, § 1(a)(3), Apr. 23, 2021, 135 Stat. 257.)

CITE AS: 21 USC 360n

§ 360n–1. Priority review for qualified infectious disease products
(a) In general
(b) Construction
(June 25, 1938, ch. 675, § 524A, as added Pub. L. 112–144, title VIII, § 802(a), July 9, 2012, 126 Stat. 1079; amended Pub. L. 114–255, div. A, title III, § 3101(a)(2)(N), Dec. 13, 2016, 130 Stat. 1154; Pub. L. 117–328, div. FF, title III, § 3212(b), Dec. 29, 2022, 136 Stat. 5826.)

CITE AS: 21 USC 360n-1

§ 360n–2. Ensuring cybersecurity of devices
(a) In general
(b) Cybersecurity requirementsThe sponsor of an application or submission described in subsection (a) shall—
(1) submit to the Secretary a plan to monitor, identify, and address, as appropriate, in a reasonable time, postmarket cybersecurity vulnerabilities and exploits, including coordinated vulnerability disclosure and related procedures;
(2) design, develop, and maintain processes and procedures to provide a reasonable assurance that the device and related systems are cybersecure, and make available postmarket updates and patches to the device and related systems to address—
(A) on a reasonably justified regular cycle, known unacceptable vulnerabilities; and
(B) as soon as possible out of cycle, critical vulnerabilities that could cause uncontrolled risks;
(3) provide to the Secretary a software bill of materials, including commercial, open-source, and off-the-shelf software components; and
(4) comply with such other requirements as the Secretary may require through regulation to demonstrate reasonable assurance that the device and related systems are cybersecure.
(c) DefinitionIn this section, the term “cyber device” means a device that—
(1) includes software validated, installed, or authorized by the sponsor as a device or in a device;
(2) has the ability to connect to the internet; and
(3) contains any such technological characteristics validated, installed, or authorized by the sponsor that could be vulnerable to cybersecurity threats.
(d) Exemption
(June 25, 1938, ch. 675, § 524B, as added Pub. L. 117–328, div. FF, title III, § 3305(a), Dec. 29, 2022, 136 Stat. 5832.)

CITE AS: 21 USC 360n-2