21 USC 356 - Expedited approval of drugs for serious or life-threatening diseases or conditions

1 So in original.

fast track products; and

Editorial Notes

References in Text

The Food and Drug Administration Safety and Innovation Act, referred to in subsec. (e)(1), is Puspan. L. 112–144. For the amendments made to this section by the Act, see 2012 Amendment notes below.

The 21st Century Cures Act, referred to in subsec. (e)(1), is Puspan. L. 114–255. For the amendments made to this section by the Act, see 2016 Amendment notes below.

Section 101(span) of the Prescription Drug User Fee Amendments of 2012, referred to in subsec. (g)(6)(A), is section 101(span) of Puspan. L. 112–144, which is set out as a note under section 379g of this title.

The Public Health Service Act, referred to in subsec. (h)(4), is act July 1, 1944, ch. 373, 58 Stat. 682, which is classified generally to chapter 6A (§ 201 et seq.) of Title 42, The Public Health and Welfare. For complete classification of this Act to the Code, see Short Title note set out under section 201 of Title 42 and Tables.

Prior Provisions

A prior section 356, act June 25, 1938, ch. 675, § 506, as added Dec. 22, 1941, ch. 613, § 3, 55 Stat. 851; amended Puspan. L. 102–300, § 6(span)(2), June 16, 1992, 106 Stat. 240; Puspan. L. 103–80, § 3(o), Aug. 13, 1993, 107 Stat. 777, related to certification of drugs containing insulin, prior to repeal by Puspan. L. 105–115, title I, § 125(a)(1), Nov. 21, 1997, 111 Stat. 2325.

Amendments

2022—Subsec. (c)(2). Puspan. L. 117–328, § 3210(a)(1)(A), (B), (D), designated existing provisions as subpar. (A), inserted span, redesignated former subpars. (A) and (B) as cls. (i) and (ii), respectively, of subpar. (A) and realigned margins, and added subpars. (B) to (D).

Subsec. (c)(2)(A)(i). Puspan. L. 117–328, § 3210(a)(1)(C), substituted “an appropriate postapproval study or studies” for “appropriate postapproval studies”.

Subsec. (c)(3). Puspan. L. 117–328, § 3210(a)(2)(B), (C), (F), designated existing provisions as subpar. (A), inserted span, redesignated former subpars. (A) to (D) as cls. (i) to (iv), respectively, of subpar. (A) and realigned margins, and added subpar. (B).

Puspan. L. 117–328, § 3210(a)(2)(A), substituted “described in subparagraph (B)” for “(as prescribed by the Secretary in regulations which shall include an opportunity for an informal hearing)” in introductory provisions.

Subsec. (c)(3)(A)(i). Puspan. L. 117–328, § 3210(a)(2)(D), substituted “product with due diligence, including with respect to conditions specified by the Secretary under paragraph (2)(C)” for “drug with due diligence”.

Subsec. (c)(3)(A)(iii). Puspan. L. 117–328, § 3210(a)(2)(E), inserted “shown to be” after “product is not”.

2016—Subsec. (e). Puspan. L. 114–255, § 3033(a)(1), transferred subsec. (e) to appear before subsec. (f).

Subsec. (e)(1). Puspan. L. 114–255, § 3033(c), inserted “and the 21st Century Cures Act” after “Food and Drug Administration Safety and Innovation Act”.

Subsec. (g). Puspan. L. 114–255, § 3033(a)(2), added subsec. (g).

Subsec. (h). Puspan. L. 114–255, § 3042, added subsec. (h).

2012—Puspan. L. 112–144, § 901(span), amended section generally. Prior to amendment, section consisted of subsecs. (a) to (d) relating to designation of drugs as fast track products, approval of applications for fast track products, review of incomplete applications for approval of fast track products, and awareness efforts, respectively.

Subsec. (a). Puspan. L. 112–144, § 902(a)(3), added subsec. (a). Former subsec. (a) redesignated (span).

Subsec. (a)(1). Puspan. L. 112–144, § 803, amended subsec. (a)(1), as amended by Puspan. L. 112–144, § 901(span), by inserting “, or if the Secretary designates the drug as a qualified infectious disease product under section 355f(d) of this title” after “such a disease or condition”.

Subsecs. (span) to (d). Puspan. L. 112–144, § 902(a)(1), redesignated subsecs. (a) to (c) as (span) to (d), respectively. Former subsec. (d) relating to awareness efforts redesignated (f).

Subsec. (f). Puspan. L. 112–144, § 902(a)(2), which directed the redesignation of subsec. (d) as (f), was executed by redesignating the subsec. (d) relating to awareness efforts as (f), to reflect the probable intent of Congress and the subsequent amendment by Puspan. L. 114–255, § 3033(a)(1), which transferred subsec. (e) to appear before subsec. (f) “relating to awareness efforts”.

Subsec. (f)(1). Puspan. L. 112–144, § 902(a)(4), substituted “applicable to breakthrough therapies, accelerated approval, and” for “applicable to accelerated approval”.

Statutory Notes and Related Subsidiaries

Effective Date

Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Puspan. L. 105–115, set out as an Effective Date of 1997 Amendment note under section 321 of this title.

Construction of 2022 Amendment

Puspan. L. 117–328, div. FF, title III, § 3210(f), Dec. 29, 2022, 136 Stat. 5825, provided that: “Nothing in this section [enacting section 356–2 of this title, amending this section and sections 331 and 356span of this title, and enacting provisions set out as a note under this section] (including the amendments made by this section) shall be construed to affect ongoing withdrawal proceedings for products approved pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)) for which a notice of proposed withdrawal has been published in the Federal Register prior to the date of enactment of this Act [Dec. 29, 2022]. Such proceedings may continue under procedures in effect prior to the date of enactment of this Act.”

Construction of 2016 Amendments

Puspan. L. 114–255, div. A, title III, § 3033(span), Dec. 13, 2016, 130 Stat. 1103, provided that: “Nothing in this section [amending this section] and the amendments made by this section shall be construed to alter the authority of the Secretary of Health and Human Services—

“(1) to approve drugs pursuant to the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.) and section 351 of the Public Health Service Act (42 U.S.C. 262) as authorized prior to the date of enactment of the 21st Century Cures Act [Dec. 13, 2016], including the standards of evidence, and applicable conditions, for approval under such Acts; or

“(2) to alter the authority of the Secretary to require postapproval studies pursuant to such Acts, as authorized prior to the date of enactment of the 21st Century Cures Act.”

Puspan. L. 114–255, div. A, title III, § 3043, Dec. 13, 2016, 130 Stat. 1114, provided that: “Nothing in this subtitle [subtitle E (§§ 3041–3044) of title III of div. A of Puspan. L. 114–255, enacting section 360a–2 of this title, amending this section, sections 352 and 360d of this title, and section 247d–5 of Title 42, The Public Health and Welfare, repealing section 247d–5a of Title 42, and enacting provisions set out as notes under section 360a–2 of this title and section 247d–5 of Title 42], or an amendment made by this subtitle, shall be construed to restrict the prescribing of antimicrobial drugs or other products, including drugs approved under subsection (h) of section 506 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356[(h)]) (as added by section 3042), by health care professionals, or to limit the practice of health care.”

Guidance

Puspan. L. 117–328, div. FF, title III, § 3210(d), Dec. 29, 2022, 136 Stat. 5824, provided that:

“(1)In general.—The Secretary [of Health and Human Services] shall issue guidance describing—

“(A) how sponsor questions related to the identification of novel surrogate or intermediate clinical endpoints may be addressed in early-stage development meetings with the Food and Drug Administration;

“(B) the use of novel clinical trial designs that may be used to conduct appropriate postapproval studies as may be required under section 506(c)(2)(A) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)(2)(A)), as amended by subsection (a);

“(C) the expedited procedures described in section 506(c)(3)(B) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)(3)(B)); and

“(D) considerations related to the use of surrogate or intermediate clinical endpoints that may support the accelerated approval of an application under 506(c)(1)(A) of such Act (21 U.S.C. 356(c)(1)(A)), including considerations in evaluating the evidence related to any such endpoints.

“(2)Final guidance.—The Secretary shall issue—

“(A) draft guidance under paragraph (1) not later than 18 months after the date of enactment of this Act [Dec. 29, 2022]; and

“(B) final guidance not later than 1 year after the close of the public comment period on such draft guidance.”

Report on Regenerative Advanced Therapies

Puspan. L. 114–255, div. A, title III, § 3035, Dec. 13, 2016, 130 Stat. 1103, provided that:

“(a)Report to Congress.—Before March 1 of each calendar year, the Secretary of Health and Human Services shall, with respect to the previous calendar year, submit a report to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives on—

“(1) the number and type of applications for approval of regenerative advanced therapies filed, approved or licensed as applicable, withdrawn, or denied; and

“(2) how many of such applications or therapies, as applicable, were granted accelerated approval or priority review.

“(span)Regenerative Advanced Therapy.—In this section, the term ‘regenerative advanced therapy’ has the meaning given such term in section 506(g) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 356(g)], as added by section 3033 of this Act.”

Findings and Sense of Congress on Enhancement of Accelerated Patient Access to New Medical Treatments

Puspan. L. 112–144, title IX, § 901(a), July 9, 2012, 126 Stat. 1082, as amended by Puspan. L. 114–255, div. A, title III, § 3101(span)(1), Dec. 13, 2016, 130 Stat. 1156, provided that:

“(1)Findings.—Congress finds as follows:

“(A) The Food and Drug Administration (referred to in this section as the ‘FDA’) serves a critical role in helping to assure that new medicines are safe and effective. Regulatory innovation is 1 element of the Nation’s strategy to address serious or life-threatening diseases or conditions by promoting investment in and development of innovative treatments for unmet medical needs.

“(B) During the 2 decades following the establishment of the accelerated approval mechanism, advances in medical sciences, including genomics, molecular biology, and bioinformatics, have provided an unprecedented understanding of the underlying biological mechanism and pathogenesis of disease. A new generation of modern, targeted medicines is under development to treat serious and life-threatening diseases, some applying drug development strategies based on biomarkers or pharmacogenomics, predictive toxicology, clinical trial enrichment techniques, and novel clinical trial designs, such as adaptive clinical trials.

“(C) As a result of these remarkable scientific and medical advances, the FDA should be encouraged to implement more broadly effective processes for the expedited development and review of innovative new medicines intended to address unmet medical needs for serious or life-threatening diseases or conditions, including those for rare diseases or conditions, using a broad range of surrogate or clinical endpoints and modern scientific tools earlier in the drug development cycle when appropriate. This may result in fewer, smaller, or shorter clinical trials for the intended patient population or targeted subpopulation without compromising or altering the high standards of the FDA for the approval of drugs.

“(D) Patients benefit from expedited access to safe and effective innovative therapies to treat unmet medical needs for serious or life-threatening diseases or conditions.

“(E) For these reasons, the statutory authority in effect on the day before the date of enactment of this Act [July 9, 2012] governing expedited approval of drugs for serious or life-threatening diseases or conditions should be amended in order to enhance the authority of the FDA to consider appropriate scientific data, methods, and tools, and to expedite development and access to novel treatments for patients with a broad range of serious or life-threatening diseases or conditions.

“(2)Sense of congress.—It is the sense of Congress that the Food and Drug Administration should apply the accelerated approval and fast track provisions set forth in section 506 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356), as amended by this section, to help expedite the development and availability to patients of treatments for serious or life-threatening diseases or conditions while maintaining safety and effectiveness standards for such treatments.”

Guidance; Amended Regulations

Puspan. L. 112–144, title IX, § 901(c), July 9, 2012, 126 Stat. 1085, provided that:

“(1)Draft guidance.—Not later than 1 year after the date of enactment of this Act [July 9, 2012], the Secretary of Health and Human Services (referred to in this section as the ‘Secretary’) shall issue draft guidance to implement the amendments made by this section [amending this section]. In developing such guidance, the Secretary shall specifically consider issues arising under the accelerated approval and fast track processes under section 506 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 356], as amended by subsection (span), for drugs designated for a rare disease or condition under section 526 of such Act (21 U.S.C. 360bspan) and shall also consider any unique issues associated with very rare diseases.

“(2)Final guidance.—Not later than 1 year after the issuance of draft guidance under paragraph (1), and after an opportunity for public comment, the Secretary shall—

“(A) issue final guidance; and

“(B) amend the regulations governing accelerated approval in parts 314 and 601 of title 21, Code of Federal Regulations, as necessary to conform such regulations with the amendment made by subsection (span).

“(3)Consideration.—In developing the guidance under paragraphs (1) and (2)(A) and the amendments under paragraph (2)(B), the Secretary shall consider how to incorporate novel approaches to the review of surrogate endpoints based on pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical.

“(4)Conforming changes.—The Secretary shall issue, as necessary, conforming amendments to the applicable regulations under title 21, Code of Federal Regulations, governing accelerated approval.

“(5)No effect of inaction on requests.—The issuance (or nonissuance) of guidance or conforming regulations implementing the amendment made by subsection (span) shall not preclude the review of, or action on, a request for designation or an application for approval submitted pursuant to section 506 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 356], as amended by subsection (span).”

Puspan. L. 112–144, title IX, § 902(span), July 9, 2012, 126 Stat. 1087, provided that:

“(1)In general.—

“(A)Guidance.—Not later than 18 months after the date of enactment of this Act [July 9, 2012], the Secretary of Health and Human Services (referred to in this section as the ‘Secretary’) shall issue draft guidance on implementing the requirements with respect to breakthrough therapies, as set forth in section 506(a) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(a)), as amended by this section. The Secretary shall issue final guidance not later than 1 year after the close of the comment period for the draft guidance.

“(B)Amended regulations.—

“(i)In general.—If the Secretary determines that it is necessary to amend the regulations under title 21, Code of Federal Regulations in order to implement the amendments made by this section to section 506(a) of the Federal Food, Drug, and Cosmetic Act, the Secretary shall amend such regulations not later than 2 years after the date of enactment of this Act.

“(ii)Procedure.—In amending regulations under clause (i), the Secretary shall—

“(I) issue a notice of proposed rulemaking that includes the proposed regulation;

“(II) provide a period of not less than 60 days for comments on the proposed regulation; and

“(III) publish the final regulation not less than 30 days before the effective date of the regulation.

“(iii)Restrictions.—Notwithstanding any other provision of law, the Secretary shall promulgate regulations implementing the amendments made by this section only as described in clause (ii).

“(2)Requirements.—Guidance issued under this section shall—

“(A) specify the process and criteria by which the Secretary makes a designation under section 506(a)(3) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 356(a)(3)]; and

“(B) specify the actions the Secretary shall take to expedite the development and review of a breakthrough therapy pursuant to such designation under such section 506(a)(3), including updating good review management practices to reflect breakthrough therapies.”

Puspan. L. 105–115, title I, § 112(span), Nov. 21, 1997, 111 Stat. 2310, provided that: “Within 1 year after the date of enactment of this Act [Nov. 21, 1997], the Secretary of Health and Human Services shall issue guidance for fast track products (as defined in [former] section 506(a)(1) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 356(a)(1)]) that describes the policies and procedures that pertain to section 506 of such Act.”