21 USC 355 - Risk evaluation and mitigation strategies

1 So in original. Probably should be followed by a semicolon.

2 So in original. Does not follow from introductory provisions.

the burden on the health care delivery system;

3 So in original.

scheduling the dispute for review, shall publish by posting on the Internet or otherwise a notice that the dispute will be reviewed by the Drug Safety Oversight Board.

4 See References in Text note below.

Editorial Notes

References in Text

For the effective date of this section, referred to in subsec. (a)(2)(A), see Effective Date note below.

Section 101(c) of the Food and Drug Administration Amendments Act of 2007, referred to in subsec. (h)(3), (4)(C)(i), is section 101(c) of Puspan. L. 110–85, which is set out as a note under section 379g of this title.

Paragraph (6), referred to in subsec. (h)(6)(C)(ii), was redesignated par. (5) of subsec. (h) of this section by Puspan. L. 112–144, title XI, § 1132(span)(4), July 9, 2012, 126 Stat. 1120.

Amendments

2022—Subsec. (e)(4)(B). Puspan. L. 117–328 struck out “for purposes of rendering drugs nonretrievable (as defined in section 1300.05 of title 21, Code of Federal Regulations (or any successor regulation))” before “if the Secretary determines”.

2019—Subsec. (g)(4)(B)(iii). Puspan. L. 116–94, § 610(f)(1), added cl. (iii).

Subsec. (i)(1)(C). Puspan. L. 116–94, § 610(f)(2), added subpar. (C) and struck out former subpar. (C) which read as follows: “Elements to assure safe use, if required under subsection (f) for the listed drug. A drug that is the subject of an abbreviated new drug application and the listed drug shall use a single, shared system under subsection (f). The Secretary may waive the requirement under the preceding sentence for a drug that is the subject of an abbreviated new drug application, and permit the applicant to use a different, comparable aspect of the elements to assure safe use, if the Secretary determines that—

“(i) the burden of creating a single, shared system outweighs the benefit of a single, system, taking into consideration the impact on health care providers, patients, the applicant for the abbreviated new drug application, and the holder of the reference drug product; or

“(ii) an aspect of the elements to assure safe use for the applicable listed drug is claimed by a patent that has not expired or is a method or process that, as a trade secret, is entitled to protection, and the applicant for the abbreviated new drug application certifies that it has sought a license for use of an aspect of the elements to assure safe use for the applicable listed drug and that it was unable to obtain a license.

A certification under clause (ii) shall include a description of the efforts made by the applicant for the abbreviated new drug application to obtain a license. In a case described in clause (ii), the Secretary may seek to negotiate a voluntary agreement with the owner of the patent, method, or process for a license under which the applicant for such abbreviated new drug application may use an aspect of the elements to assure safe use, if required under subsection (f) for the applicable listed drug, that is claimed by a patent that has not expired or is a method or process that as a trade secret is entitled to protection.”

Subsec. (i)(3). Puspan. L. 116–94, § 610(f)(3), added par. (3).

Subsec. (l). Puspan. L. 116–94, § 610(d), added subsec. (l).

Subsec. (m). Puspan. L. 116–94, § 610(f)(4), added subsec. (m).

2018—Subsec. (span)(1)(E). Puspan. L. 115–271, § 3041(a), substituted “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” for “of the drug”.

Subsec. (e)(4). Puspan. L. 115–271, § 3032(a), added par. (4).

Subsec. (f)(2)(C)(iii). Puspan. L. 115–271, § 3032(span), added cl. (iii).

Subsec. (i)(1)(B), (C). Puspan. L. 115–271, § 3032(c)(1), added subpar. (B) and redesignated former subpar. (B) as (C).

Subsec. (i)(2)(B), (C). Puspan. L. 115–271, § 3032(c)(2), added subpar. (B) and redesignated former subpar. (B) as (C).

2017—Subsec. (e)(3)(B). Puspan. L. 115–52, § 606(1), struck out “; or” at end.

Subsec. (e)(3)(D). Puspan. L. 115–52, § 606(2), (3), added subpar. (D).

2016—Subsec. (f)(5). Puspan. L. 114–255, § 3075(c)(1), inserted “or other advisory committee” after “(or successor committee)” in introductory provisions.

Subsec. (f)(5)(B). Puspan. L. 114–255, § 3075(c)(2), substituted “periodically” for “at least annually,” in introductory provisions.

Subsec. (h)(2)(A)(iii). Puspan. L. 114–255, § 3101(a)(2)(C)(i), substituted, in span, “labeling” for “label” and in text, “approved safety labeling changes” for “approved safety label changes”, “responsible person” for “sponsor”, and “a safety labeling change” for “a safety label change”.

Subsec. (h)(8). Puspan. L. 114–255, § 3101(a)(2)(C)(ii), struck out period after “(7)”.

2013—Subsec. (f)(7). Puspan. L. 113–5, § 302(c)(1), struck out par. (7) which related to waiver of subsec. (f) requirements in public health emergencies.

Subsec. (k). Puspan. L. 113–5, § 302(c)(2), added subsec. (k).

2012—Subsec. (g)(1). Puspan. L. 112–144, § 1132(a)(1), struck out “, and propose a modification to,” after “an assessment of”.

Subsec. (g)(2). Puspan. L. 112–144, § 1132(a)(2)(A), in introductory provisions, struck out “, subject to paragraph (5),” after “shall” and “, and may propose a modification to,” after “an assessment of”.

Subsec. (g)(2)(C). Puspan. L. 112–144, § 1132(a)(2)(B), substituted “an assessment is needed to evaluate whether the approved strategy should be modified to—” and cls. (i) and (ii) for “new safety or effectiveness information indicates that—

“(i) an element under subsection (d) or (e) should be modified or included in the strategy; or

“(ii) an element under subsection (f) should be modified or included in the strategy; or”.

Subsec. (g)(2)(D). Puspan. L. 112–144, § 1132(a)(2)(C), struck out subpar. (D) which read as follows: “within 15 days when ordered by the Secretary, in consultation with the offices described in subsection (c)(2), if the Secretary determines that there may be a cause for action by the Secretary under section 355(e) of this title.”

Subsec. (g)(3). Puspan. L. 112–144, § 1132(a)(3), substituted “for a drug shall include, with respect to each goal included in the strategy, an assessment of the extent to which the approved strategy, including each element of the strategy, is meeting the goal or whether 1 or more such goals or such elements should be modified.” for “for a drug shall include—” and struck out subpars. (A) to (C) which related to assessment of elements to assure safe use, postapproval studies, and postapproval clinical trials.

Subsec. (g)(4). Puspan. L. 112–144, § 1132(a)(4), amended par. (4) generally. Prior to amendment, text read as follows: “A modification (whether an enhancement or a reduction) to the approved risk evaluation and mitigation strategy for a drug may include the addition or modification of any element under subsection (d) or the addition, modification, or removal of any element under subsection (e) or (f), such as—

“(A) modifying the timetable for assessments of the strategy as provided in subsection (d)(3), including to eliminate assessments; or

“(B) adding, modifying, or removing an element to assure safe use under subsection (f).”

Subsec. (h). Puspan. L. 112–144, § 1132(span)(1), inserted “and modifications” after “review of assessments” in span.

Subsec. (h)(1). Puspan. L. 112–144, § 1132(span)(2), inserted “and proposed modification to” after “under subsection (a) and each assessment of” and “, and, if necessary, promptly initiate discussions with the responsible person about such proposed strategy, assessment, or modification” after “subsection (g)”.

Subsec. (h)(2). Puspan. L. 112–144, § 1132(span)(3), (4), redesignated par. (3) as (2) and struck out former par. (2). Prior to amendment, text of par. (2) read as follows: “The Secretary, in consultation with the offices described in subsection (c)(2), shall initiate discussions with the responsible person for purposes of this subsection to determine a strategy not later than 60 days after any such assessment is submitted or, in the case of an assessment submitted under subsection (g)(2)(D), not later than 30 days after such assessment is submitted.”

Subsec. (h)(2)(A). Puspan. L. 112–144, § 1132(span)(5)(A), amended subpar. (A) generally. Prior to amendment, subpar. (A) related to Secretary’s description of any required risk evaluation and mitigation strategy for a drug as part of the action letter on the application or in an order.

Subsec. (h)(2)(C). Puspan. L. 112–144, § 1132(span)(5)(B), amended subpar. (C) generally. Prior to amendment, text read as follows: “Any action letter described in subparagraph (A)(i) or order described in subparagraph (A)(ii) shall be made publicly available.”

Subsec. (h)(3), (4). Puspan. L. 112–144, § 1132(span)(4), redesignated pars. (4) and (5) as (3) and (4), respectively. Former par. (3) redesignated (2).

Subsec. (h)(4)(A)(i). Puspan. L. 112–144, § 1132(span)(6)(A), substituted “The responsible” for “Not earlier than 15 days, and not later than 35 days, after discussions under paragraph (2) have begun, the responsible” and inserted “, after the sponsor is required to make a submission under subsection (a)(2) or (g),” before “request in writing”.

Subsec. (h)(4)(I). Puspan. L. 112–144, § 1132(span)(6)(B), substituted “if the Secretary has complied with the timing requirements of scheduling review by the Drug Safety Oversight Board, providing a written recommendation, and issuing an action letter under subparagraphs (B), (F), and (G), respectively.” for “if the Secretary—” and struck out cls. (i) and (ii) which read as follows:

“(i) has initiated the discussions described under paragraph (2) not less than 60 days before such action deadline; and

“(ii) has complied with the timing requirements of scheduling review by the Drug Safety Oversight Board, providing a written recommendation, and issuing an action letter under subparagraphs (B), (F), and (G), respectively.”

Subsec. (h)(5). Puspan. L. 112–144, § 1132(span)(4), (7), redesignated par. (6) as (5) and substituted “subparagraph (B) or (C)” for “any of subparagraphs (B) through (D)” in subpar. (A) and “paragraph (3) or (4)” for “paragraph (4) or (5)” in subpar. (C). Former par. (5) redesignated (4).

Subsec. (h)(6), (7). Puspan. L. 112–144, § 1132(span)(4), redesignated pars. (7) and (8) as (6) and (7), respectively. Former par. (6) redesignated (5).

Subsec. (h)(8), (9). Puspan. L. 112–144, § 1132(span)(4), (8), redesignated par. (9) as (8) and substituted “paragraphs (6) and (7).” for “paragraphs (7) and (8)”. Former par. (8) redesignated (7).

Statutory Notes and Related Subsidiaries

Effective Date

Section effective 180 days after Sept. 27, 2007, see section 909 of Puspan. L. 110–85, set out as an Effective Date of 2007 Amendment note under section 331 of this title.

Evidence-Based Opioid Analgesic Prescribing Guidelines and Report

Puspan. L. 115–271, title III, § 3002, Oct. 24, 2018, 132 Stat. 3934, provided that:

“(a)Guidelines.—The Commissioner of Food and Drugs shall develop evidence-based opioid analgesic prescribing guidelines for the indication-specific treatment of acute pain only for the relevant therapeutic areas where such guidelines do not exist.

“(span)Public Input.—In developing the guidelines under subsection (a), the Commissioner of Food and Drugs shall—

“(1) consult with stakeholders, which may include conducting a public meeting of medical professional societies (including any State-based societies), health care providers, State medical boards, medical specialties including pain medicine specialty societies, patient groups, pharmacists, academic or medical research entities, and other entities with experience in health care, as appropriate;

“(2) collaborate with the Director of the Centers for Disease Control and Prevention, as applicable and appropriate, and other Federal agencies with relevant expertise as appropriate; and

“(3) provide for a notice and comment period consistent with section 701(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 371(h)) for the submission of comments by the public.

“(c)Report.—Not later than 1 year after the date of enactment of this Act [Oct. 24, 2018], or, if earlier, at the time the guidelines under subsection (a) are finalized, the Commissioner of Food and Drugs 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, and post on the public website of the Food and Drug Administration, a report on how the Food and Drug Administration will utilize the guidelines under subsection (a) to protect the public health and a description of the public health need with respect to each such indication-specific treatment guideline.

“(d)Updates.—The Commissioner of Food and Drugs shall periodically—

“(1) update the guidelines under subsection (a), informed by public input described in subsection (span); and

“(2) submit to the committees specified in subsection (c) and post on the public website of the Food and Drug Administration an updated report under such subsection.

“(e)Statement To Accompany Guidelines and Recommendations.—The Commissioner of Food and Drugs shall ensure that opioid analgesic prescribing guidelines and other recommendations developed under this section are accompanied by a clear statement that such guidelines or recommendations, as applicable—

“(1) are intended to help inform clinical decisionmaking by prescribers and patients; and

“(2) are not intended to be used for the purposes of restricting, limiting, delaying, or denying coverage for, or access to, a prescription issued for a legitimate medical purpose by an individual practitioner acting in the usual course of professional practice.”

Prescriber Education

Puspan. L. 114–198, title I, § 106(span), July 22, 2016, 130 Stat. 703, provided that: “Not later than 1 year after the date of the enactment of this Act [July 22, 2016], the Secretary [of Health and Human Services], acting through the Commissioner of Food and Drugs, as part of the Food and Drug Administration’s evaluation of the Extended-Release/Long-Acting Opioid Analgesics Risk Evaluation and Mitigation Strategy, and in consultation with relevant stakeholders, shall develop recommendations regarding education programs for prescribers of opioids pursuant to section 505–1 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355–1), including recommendations on—

“(1) which prescribers should participate in such programs; and

“(2) how often participation in such programs is necessary.”

Guidance

Puspan. L. 112–144, title XI, § 1132(c), July 9, 2012, 126 Stat. 1122, provided that: “Not later than 1 year after the date of enactment of this Act [July 9, 2012], the Secretary of Health and Human Services shall issue guidance that, for purposes of section 505–1(h)(2)(A) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355–1(h)(2)(A)), describes the types of modifications to approved risk evaluation and mitigation strategies that shall be considered to be minor modifications of such strategies.”