21 USC 360 - FDA rare neurodegenerative disease grant program

Collapse to view only § 360ee-1. FDA rare neurodegenerative disease grant program

§ 360aa. Recommendations for investigations of drugs for rare diseases or conditions
§ 360bb. Designation of drugs for rare diseases or conditions
§ 360cc. Protection for drugs for rare diseases or conditions
§ 360dd. Open protocols for investigations of drugs for rare diseases or conditions
§ 360ee. Grants and contracts for development of drugs for rare diseases and conditions
§ 360ee-1. FDA rare neurodegenerative disease grant program
§ 360ff. Priority review to encourage treatments for rare pediatric diseases
§ 360ff-1. Targeted drugs for rare diseases

§ 360aa. Recommendations for investigations of drugs for rare diseases or conditions

(a) Request by sponsor; response by Secretary

The sponsor of a drug for a disease or condition which is rare in the States may request the Secretary to provide written recommendations for the non-clinical and clinical investigations which must be conducted with the drug before—

(1) it may be approved for such disease or condition under section 355 of this title, or

(2) if the drug is a biological product, it may be licensed for such disease or condition under section 262 of title 42.

If the Secretary has reason to believe that a drug for which a request is made under this section is a drug for a disease or condition which is rare in the States, the Secretary shall provide the person making the request written recommendations for the non-clinical and clinical investigations which the Secretary believes, on the basis of information available to the Secretary at the time of the request under this section, would be necessary for approval of such drug for such disease or condition under section 355 of this title or licensing of such drug for such disease or condition under section 262 of title 42.

(b) Regulations

(June 25, 1938, ch. 675, § 525, as added Pub. L. 97–414, § 2(a), Jan. 4, 1983, 96 Stat. 2049; amended Pub. L. 99–91, § 3(a)(1), Aug. 15, 1985, 99 Stat. 387; Pub. L. 105–115, title I, § 125(b)(2)(F), (G), Nov. 21, 1997, 111 Stat. 2325, 2326.)

§ 360bb. Designation of drugs for rare diseases or conditions

(a) Request by sponsor; preconditions; “rare disease or condition” defined

(1) The manufacturer or the sponsor of a drug may request the Secretary to designate the drug as a drug for a rare disease or condition. A request for designation of a drug shall be made before the submission of an application under section 355(b) of this title for the drug, or the submission of an application for licensing of the drug under section 262 of title 42. If the Secretary finds that a drug for which a request is submitted under this subsection is being or will be investigated for a rare disease or condition and—

(A) if an application for such drug is approved under section 355 of this title, or

(B) if a license for such drug is issued under section 262 of title 42,

the approval, certification, or license would be for use for such disease or condition, the Secretary shall designate the drug as a drug for such disease or condition. A request for a designation of a drug under this subsection shall contain the consent of the applicant to notice being given by the Secretary under subsection (b) 1

1 See References in Text note below.

respecting the designation of the drug.

(2) For purposes of paragraph (1), the term “rare disease or condition” means any disease or condition which (A) affects less than 200,000 persons in the United States, or (B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug. Determinations under the preceding sentence with respect to any drug shall be made on the basis of the facts and circumstances as of the date the request for designation of the drug under this subsection is made.

(b) Notification of discontinuance of drug or application as conditionA designation of a drug under subsection (a) shall be subject to the condition that—

(1) if an application was approved for the drug under section 355(b) of this title or a license was issued for the drug under section 262 of title 42, the manufacturer of the drug will notify the Secretary of any discontinuance of the production of the drug at least one year before discontinuance, and

(2) if an application has not been approved for the drug under section 355(b) of this title or a license has not been issued for the drug under section 262 of title 42 and if preclinical investigations or investigations under section 355(i) of this title are being conducted with the drug, the manufacturer or sponsor of the drug will notify the Secretary of any decision to discontinue active pursuit of approval of an application under section 355(b) of this title or approval of a license under section 262 of title 42.

(d) Regulations

(June 25, 1938, ch. 675, § 526, as added Pub. L. 97–414, § 2(a), Jan. 4, 1983, 96 Stat. 2050; amended Pub. L. 98–551, § 4(a), Oct. 30, 1984, 98 Stat. 2817; Pub. L. 99–91, § 3(a)(2), Aug. 15, 1985, 99 Stat. 387; Pub. L. 100–290, § 2, Apr. 18, 1988, 102 Stat. 90; Pub. L. 105–115, title I, § 125(b)(2)(H), (I), Nov. 21, 1997, 111 Stat. 2326.)

§ 360cc. Protection for drugs for rare diseases or conditions

(a) Exclusive approval, certification, or license

Except as provided in subsection (b), if the Secretary—

(1) approves an application filed pursuant to section 355 of this title, or

(2) issues a license under section 262 of title 42

for a drug designated under section 360bb of this title for a rare disease or condition, the Secretary may not approve another application under section 355 of this title or issue another license under section 262 of title 42 for the same drug for the same disease or condition for a person who is not the holder of such approved application or of such license until the expiration of seven years from the date of the approval of the approved application or the issuance of the license. Section 355(c)(2) 1

1 See References in Text note below.

of this title does not apply to the refusal to approve an application under the preceding sentence.

(b) Exceptions

During the 7-year period described in subsection (a) for an approved application under section 355 of this title or license under section 262 of title 42, the Secretary may approve an application or issue a license for a drug that is otherwise the same, as determined by the Secretary, as the already approved drug for the same rare disease or condition if—

(1) the Secretary finds, after providing the holder of exclusive approval or licensure notice and opportunity for the submission of views, that during such period the holder of the exclusive approval or licensure cannot ensure the availability of sufficient quantities of the drug to meet the needs of persons with the disease or condition for which the drug was designated; or

(2) the holder provides the Secretary in writing the consent of such holder for the approval of other applications or the issuance of other licenses before the expiration of such seven-year period.

(1) In general

(2) Definition

(3) Applicability

(d) Regulations

(e) Demonstration of clinical superiority standard

To assist sponsors in demonstrating clinical superiority as described in subsection (c), the Secretary—

(1) upon the designation of any drug under section 360bb of this title, shall notify the sponsor of such drug in writing of the basis for the designation, including, as applicable, any plausible hypothesis offered by the sponsor and relied upon by the Secretary that the drug is clinically superior to a previously approved drug; and

(2) upon granting exclusive approval or licensure under subsection (a) on the basis of a demonstration of clinical superiority as described in subsection (c), shall publish a summary of the clinical superiority findings.

(June 25, 1938, ch. 675, § 527, as added Pub. L. 97–414, § 2(a), Jan. 4, 1983, 96 Stat. 2050; amended Pub. L. 98–417, title I, § 102(b)(6), Sept. 24, 1984, 98 Stat. 1593; Pub. L. 99–91, §§ 2, 3(a)(3), Aug. 15, 1985, 99 Stat. 387, 388; Pub. L. 103–80, § 3(v), Aug. 13, 1993, 107 Stat. 778; Pub. L. 105–115, title I, § 125(b)(2)(J), (K), Nov. 21, 1997, 111 Stat. 2326; Pub. L. 107–281, § 4, Nov. 6, 2002, 116 Stat. 1993; Pub. L. 115–52, title VI, § 607(a), Aug. 18, 2017, 131 Stat. 1049; Pub. L. 116–260, div. BB, title III, § 323, Dec. 27, 2020, 134 Stat. 2933.)

§ 360dd. Open protocols for investigations of drugs for rare diseases or conditions

If a drug is designated under section 360bb of this title as a drug for a rare disease or condition and if notice of a claimed exemption under section 355(i) of this title or regulations issued thereunder is filed for such drug, the Secretary shall encourage the sponsor of such drug to design protocols for clinical investigations of the drug which may be conducted under the exemption to permit the addition to the investigations of persons with the disease or condition who need the drug to treat the disease or condition and who cannot be satisfactorily treated by available alternative drugs.

(June 25, 1938, ch. 675, § 528, as added Pub. L. 97–414, § 2(a), Jan. 4, 1983, 96 Stat. 2051.)

§ 360ee. Grants and contracts for development of drugs for rare diseases and conditions

(a) Authority of Secretary

(b) DefinitionsFor purposes of subsection (a):

(1) The term “qualified testing” means—

(A) human clinical testing—

(i) which is carried out under an exemption for a drug for a rare disease or condition under section 355(i) of this title (or regulations issued under such section); and

(ii) which occurs before the date on which an application with respect to such drug is submitted under section 355(b) of this title or under section 262 of title 42;

(B) preclinical testing involving a drug for a rare disease or condition which occurs after the date such drug is designated under section 360bb of this title and before the date on which an application with respect to such drug is submitted under section 355(b) of this title or under section 262 of title 42; and

(C) prospectively planned and designed observational studies and other analyses conducted to assist in the understanding of the natural history of a rare disease or condition and in the development of a therapy, including studies and analyses to—

(i) develop or validate a drug development tool related to a rare disease or condition; or

(ii) understand the full spectrum of the disease manifestations, including describing genotypic and phenotypic variability and identifying and defining distinct subpopulations affected by a rare disease or condition.

(2) The term “rare disease or condition” means (1) in the case of a drug, any disease or condition which (A) affects less than 200,000 persons in the United States, or (B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug, (2) in the case of a medical device, any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical device for such disease or condition will be developed without assistance under subsection (a), and (3) in the case of a medical food, any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical food for such disease or condition will be developed without assistance under subsection (a). Determinations under the preceding sentence with respect to any drug shall be made on the basis of the facts and circumstances as of the date the request for designation of the drug under section 360bb of this title is made.

(3) The term “medical food” means a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.

(Pub. L. 97–414, § 5, Jan. 4, 1983, 96 Stat. 2056; Pub. L. 98–551, § 4(b), Oct. 30, 1984, 98 Stat. 2817; Pub. L. 99–91, § 5, Aug. 15, 1985, 99 Stat. 391; Pub. L. 100–290, § 3(a)–(c), Apr. 18, 1988, 102 Stat. 90, 91; Pub. L. 105–115, title I, § 125(b)(2)(N), Nov. 21, 1997, 111 Stat. 2326; Pub. L. 107–281, § 3, Nov. 6, 2002, 116 Stat. 1993; Pub. L. 110–85, title XI, § 1112(b), Sept. 27, 2007, 121 Stat. 976; Pub. L. 112–144, title IX, § 906, July 9, 2012, 126 Stat. 1092; Pub. L. 114–255, div. A, title III, § 3015, Dec. 13, 2016, 130 Stat. 1094; Pub. L. 115–52, title VI, § 603, Aug. 18, 2017, 131 Stat. 1048; Pub. L. 117–180, div. F, title V, § 5006, Sept. 30, 2022, 136 Stat. 2167; Pub. L. 117–229, div. C, title III, § 307, Dec. 16, 2022, 136 Stat. 2312; Pub. L. 117–328, div. FF, title III, § 3107, Dec. 29, 2022, 136 Stat. 5808.)

§ 360ee–1. FDA rare neurodegenerative disease grant programThe Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs, shall award grants and contracts to public and private entities to cover the costs of research on, and development of interventions intended to prevent, diagnose, mitigate, treat, or cure, amyotrophic lateral sclerosis and other rare neurodegenerative diseases in adults and children, including costs incurred with respect to the development and critical evaluation of tools, methods, and processes—

(1) to characterize such neurodegenerative diseases and their natural history;

(2) to identify molecular targets for such neurodegenerative diseases; and

(3) to increase efficiency and productivity of clinical development of therapies, including through—

(A) the use of master protocols and adaptive and add-on clinical trial designs; and

(B) efforts to establish new or leverage existing clinical trial networks.

(Pub. L. 117–79, § 5, Dec. 23, 2021, 135 Stat. 1537.)

§ 360ff. Priority review to encourage treatments for rare pediatric diseases

(a) DefinitionsIn this section:

(1) Priority review

(2) Priority review voucher

(3) Rare pediatric diseaseThe term “rare pediatric disease” means a disease that meets each of the following criteria:

(A) The disease is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents.

(B) The disease is a rare disease or condition, within the meaning of section 360bb of this title.

(4) Rare pediatric disease product applicationThe term “rare pediatric disease product application” means a human drug application, as defined in section 379g(1) of this title, that—

(A) is for a drug or biological product that is for the prevention or treatment of a rare pediatric disease;

(B)

(i) is for such a drug—(I) that contains no 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 previously approved in any other application under subsection (b)(1), (b)(2), or (j) of section 355 of this title; and(II) that is the subject of an application submitted under section 355(b)(1) of this title; or

(ii) is for such a biological product—(I) that contains no active ingredient that has been previously approved in any other application under section 351(a) or 351(k) of the Public Health Service Act [42 U.S.C. 262(a), 262(k)]; and(II) that is the subject of an application submitted under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)];

(D) that 1

1 So in original. The word “that” probably should not appear.

relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population;

(E) that 1 does not seek approval for an adult indication in the original rare pediatric disease product application; and

(F) is approved after September 30, 2016.

(b) Priority review voucher

(1) In general

(2) Transferability

(A) In general

(B) Notification of transfer

(3) Limitation

(4) Notification

(A) Sponsor of a rare pediatric disease product

(i) In general

(ii) Applications submitted but not yet approvedThe sponsor of a rare pediatric disease product application that was submitted and that has not been approved as of September 30, 2016, shall be considered eligible for a priority review voucher, if—(I) such sponsor has submitted such rare pediatric disease product application—(aa) on or after the date that is 90 days after July 9, 2012; and(bb) on or before September 30, 2016; and(II) such application otherwise meets the criteria for a priority review voucher under this section.

(B) Sponsor of a drug application using a priority review voucher

(i) In general

(ii) Transfer after notice

(5) Termination of authorityThe Secretary may not award any priority review vouchers under paragraph (1) after December 20, 2024, unless the rare pediatric disease product application—

(A) is for a drug that, not later than December 20, 2024, is designated under subsection (d) as a drug for a rare pediatric disease; and

(B) is, not later than September 30, 2026, approved under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)].

(1) In general

(2) Fee amountThe amount of the priority review user fee shall be determined each fiscal year by the Secretary, based on the difference between—

(A) the average cost incurred by the Food and Drug Administration in the review of a human drug application subject to priority review in the previous fiscal year; and

(B) the average cost incurred by the Food and Drug Administration in the review of a human drug application that is not subject to priority review in the previous fiscal year.

(3) Annual fee setting

(4) Payment

(A) In general

(B) Complete application

(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 appropriations Acts.

(d) Designation process

(1) In generalUpon the request of the manufacturer or the sponsor of a new drug, the Secretary may designate—

(A) the new drug as a drug for a rare pediatric disease; and

(B) the application for the new drug as a rare pediatric disease product application.

(2) Request for designation

(3) Determination by SecretaryNot later than 60 days after a request is submitted under paragraph (1), the Secretary shall determine whether—

(A) the disease or condition that is the subject of such request is a rare pediatric disease; and

(B) the application for the new drug is a rare pediatric disease product application.

(e) Marketing of rare pediatric disease products

(1) Revocation

(2) Postapproval production reportThe sponsor of an approved rare pediatric disease product shall submit a report to the Secretary not later than 5 years after the approval of the applicable rare pediatric disease product application. Such report shall provide the following information, with respect to each of the first 4 years after approval of such product:

(A) The estimated population in the United States suffering from the rare pediatric disease.

(B) The estimated demand in the United States for such rare pediatric disease product.

(f) Notice and report

(1) Notice of issuance of voucher and approval of products under voucherThe Secretary shall publish a notice in the Federal Register and on the Internet Web site of the Food and Drug Administration not later than 30 days after the occurrence of each of the following:

(A) The Secretary issues a priority review voucher under this section.

(B) The Secretary approves a drug pursuant to an application submitted under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for which the sponsor of the application used a priority review voucher under this section.

(2) NotificationIf, after the last day of the 1-year period that begins on the date that the Secretary awards the third rare pediatric disease priority voucher under this section, a sponsor of an application submitted under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for a drug uses a priority review voucher under this section for such application, 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 document—

(A) notifying such Committees of the use of such voucher; and

(B) identifying the drug for which such priority review voucher is used.

(g) Eligibility for other programs

(h) Relation to other provisions

(i) GAO study and report

(1) Study

(A) In general

(B) Contents of studyIn conducting the study under subparagraph (A), the Comptroller General shall examine the following:

(i) The indications for which each rare disease product for which a priority review voucher was awarded was approved under section 355 of this title or section 351 of the Public Health Service Act [42 U.S.C. 262].

(ii) Whether, and to what extent, an unmet need related to the treatment or prevention of a rare pediatric disease was met through the approval of such a rare disease product.

(iii) The value of the priority review voucher if transferred.

(iv) Identification of each drug for which a priority review voucher was used.

(v) The length of the period of time between the date on which a priority review voucher was awarded and the date on which it was used.

(2) Report

(June 25, 1938, ch. 675, § 529, as added Pub. L. 112–144, title IX, § 908, July 9, 2012, 126 Stat. 1094; amended Pub. L. 114–113, div. A, title VII, § 765, Dec. 18, 2015, 129 Stat. 2286; Pub. L. 114–229, § 2(a), Sept. 30, 2016, 130 Stat. 943; Pub. L. 114–255, div. A, title III, § 3013(a), Dec. 13, 2016, 130 Stat. 1093; Pub. L. 116–159, div. C, title I, § 2105, Oct. 1, 2020, 134 Stat. 729; Pub. L. 116–215, div. B, title II, § 1211, Dec. 11, 2020, 134 Stat. 1045; Pub. L. 116–260, div. BB, title III, § 321, Dec. 27, 2020, 134 Stat. 2932; Pub. L. 117–9, § 1(a)(4), Apr. 23, 2021, 135 Stat. 257; Pub. L. 118–83, div. B, title II, § 202, Sept. 26, 2024, 138 Stat. 1538.)

§ 360ff–1. Targeted drugs for rare diseases

(a) PurposeThe purpose of this section, through the approach provided for in subsection (b), is to—

(1) facilitate the development, review, and approval of genetically targeted drugs and variant protein targeted drugs to address an unmet medical need in one or more patient subgroups, including subgroups of patients with different mutations of a gene, with respect to rare diseases or conditions that are serious or life-threatening; and

(2) maximize the use of scientific tools or methods, including surrogate endpoints and other biomarkers, for such purposes.

(b) Leveraging of data from previously approved drug application or applicationsThe Secretary may, consistent with applicable standards for approval under this chapter or 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)(1) of this title or section 351(a) of the Public Health Service Act for a genetically targeted drug or a variant protein targeted drug to rely upon data and information—

(1) previously developed by the same sponsor (or another sponsor that has provided the sponsor with a contractual right of reference to such data and information); and

(2) submitted by a sponsor described in paragraph (1) in support of one or more previously approved applications that were submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act,

for a drug that incorporates or utilizes the same or similar genetically targeted technology as the drug or drugs that are the subject of an application or applications described in paragraph (2) or for a variant protein targeted drug that is the same or incorporates or utilizes the same variant protein targeted drug, as the drug or drugs that are the subject of an application or applications described in paragraph (2).

(1) the term “genetically targeted drug” means a drug that—

(A) is the subject of an application under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for the treatment of a rare disease or condition (as such term is defined in section 360bb of this title) that is serious or life-threatening;

(B) may result in the modulation (including suppression, up-regulation, or activation) of the function of a gene or its associated gene product; and

(2) the term “genetically targeted technology” means a technology comprising non-replicating nucleic acid or analogous compounds with a common or similar chemistry that is intended to treat one or more patient subgroups, including subgroups of patients with different mutations of a gene, with the same disease or condition, including a disease or condition due to other variants in the same gene; and

(3) the term “variant protein targeted drug” means a drug that—

(B) modulates the function of a product of a mutated gene where such mutation is responsible in whole or in part for a given disease or condition; and

(C) is intended to treat one or more patient subgroups, including subgroups of patients with different mutations of a gene, with the same disease or condition.

(d) Rule of constructionNothing in this section shall be construed to—

(1) alter the authority of the Secretary to approve drugs pursuant to this chapter or section 351 of the Public Health Service Act [42 U.S.C. 262] (as authorized prior to December 13, 2016), including the standards of evidence, and applicable conditions, for approval under such applicable chapter or Act; or

(2) confer any new rights, beyond those authorized under this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.] prior to December 13, 2016, with respect to the permissibility of a sponsor referencing information contained in another application submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)].

(June 25, 1938, ch. 675, § 529A, as added Pub. L. 114–255, div. A, title III, § 3012, Dec. 13, 2016, 130 Stat. 1091.)