§357 — Title 21 Food and Drugs | U.S. Code

Summary

The Secretary must set up a step-by-step process to decide if a tool used in drug development can be “qualified” for a specific use. A requestor starts by sending a letter of intent. The Secretary can accept or decline it. If accepted, the requestor sends a qualification plan, which the Secretary can accept or decline. If that is accepted, the requestor sends a full qualification package. The Secretary decides whether to accept the package for review, and if accepted, conducts a full review. Acceptance decisions can be based on scientific merit. Not accepting a submission is not the same as denying final qualification. The Secretary may speed up reviews for tools tied to severe, rare, or common conditions, where few treatments exist, or tools identified as public health priorities. The Secretary may work with and get advice from biomedical research consortia. If the full package passes review, the Secretary decides whether the tool is qualified based on the science in the package. A qualified tool may be used by anyone in the approved context to help get drug approvals or to support investigational drug studies. The Secretary can rescind or change a qualification if new information shows the tool is no longer appropriate, and must offer the requestor a meeting before that change takes effect. The FDA must post information on its website at least twice a year about submissions, review stage and dates, use of outside experts, the submissions and data, written decisions, rescissions or changes, summary reviews, and a list of qualified tools and surrogate endpoints; that posted information is treated as an authorized public disclosure under section 1905 of title 18. The Secretary does not have to post trade secrets or national-security-sensitive information, but must note when such information is withheld. This process does not change the usual evidence standards for drug approval or limit the Secretary’s existing approval or licensing authority as it stood before December 13, 2016. The law defines several terms in one line each: biomarker — a measured biological characteristic (includes surrogate endpoints); biomedical research consortia — collaborative public‑private groups of experts and stakeholders; clinical outcome assessment — a measure of symptoms, mental state, or how a disease affects function (includes patient reports); context of use — the specific way a tool will be used in drug development; drug development tool — includes biomarkers, clinical outcome assessments, and other methods or materials the Secretary finds useful; patient‑reported outcome — a health report coming directly from the patient; qualification/qualified — a Secretary’s decision that a tool can be relied on for a stated context; requestor — the person or group asking for qualification; surrogate endpoint — a marker that either is known to predict clinical benefit (can support traditional approval) or is reasonably likely to predict benefit (can support accelerated approval).

Title 21, §357

Food and Drugs — Source: USLM XML via OLRC

(a)(1)The 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)(A)Subparagraphs (B), (C), and (D) shall apply with respect to the treatment of a letter of intent, a qualification plan, or a full qualification package submitted under paragraph (1) (referred to in this paragraph as “qualification submissions”).

(B)The Secretary shall determine whether to accept a qualification submission based on factors which may include the scientific merit of the qualification submission. A determination not to accept a submission under paragraph (1) shall not be construed as a final determination by the Secretary under this section regarding the qualification of a drug development tool for its proposed context of use.

(C)The 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)The Secretary may, for purposes of the review of qualification submissions, through the use of cooperative agreements, grants, or other appropriate mechanisms, consult with biomedical research consortia and may consider the recommendations of such consortia with respect to the review of any qualification plan submitted under paragraph (1) or the review of any full qualification package under paragraph (3).

(3)The 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)The Secretary shall determine whether a drug development tool is qualified for a proposed context of use based on the scientific merit of a full qualification package reviewed under paragraph (3).

(b)(1)A drug development tool determined to be qualified under subsection (a)(4) for a proposed context of use specified by the requestor may be used by any person in such context of use for the purposes described in paragraph (2).

(2)Subject 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)(A)The Secretary may rescind or modify a determination under this section to qualify a drug development tool if the Secretary determines that the drug development tool is not appropriate for the proposed context of use specified by the requestor. Such a determination may be based on new information that calls into question the basis for such qualification.

(B)If the Secretary rescinds or modifies under subparagraph (A) a determination to qualify a drug development tool, the requestor involved shall, on request, be granted a meeting with the Secretary to discuss the basis of the Secretary’s decision to rescind or modify the determination before the effective date of the rescission or modification.

(c)(1)Subject 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)Information made publicly available by the Secretary under paragraph (1) shall be considered a disclosure authorized by law for purposes of section 1905 of title 18.

(3)(A)Nothing 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 section 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)In the case that the Secretary, pursuant to subparagraph (A)(ii), does not make information publicly available, the Secretary shall provide on the internet website of the Food and Drug Administration an acknowledgment of the information that has not been disclosed, pursuant to subparagraph (A)(ii).

(d)Nothing 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)In this section:

(1)The 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)The term “biomedical research consortia” means collaborative groups that may take the form of public-private partnerships and may include government agencies, institutions of higher education (as defined in section 1001(a) of title 20), patient advocacy groups, industry representatives, clinical and scientific experts, and other relevant entities and individuals.

(3)The 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)The term “context of use” means, with respect to a drug development tool, the circumstances under which the drug development tool is to be used in drug development and regulatory review.

(5)The 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)The term “patient-reported outcome” means a measurement based on a report from a patient regarding the status of the patient’s health condition without amendment or interpretation of the patient’s report by a clinician or any other person.

(7)The terms “qualification” and “qualified” mean a determination by the Secretary that a drug development tool and its proposed context of use can be relied upon to have a specific interpretation and application in drug development and regulatory review under this chapter.

(8)The term “requestor” means an entity or entities, including a drug sponsor or a biomedical research consortia, seeking to qualify a drug development tool for a proposed context of use under this section.

(9)The term “surrogate endpoint” means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and—

(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.

Notes & Related Subsidiaries

Editorial Notes

References in Text

The Public Health Service Act, referred to in subsec. (d)(2), 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 357, act

June 25, 1938, ch. 675, § 507, as added

July 6, 1945, ch. 281, § 3, 59 Stat. 463; amended Mar. 10, 1947, ch. 16, § 3, 61 Stat. 12;

July 13, 1949, ch. 305, § 2, 63 Stat. 409; Aug. 5, 1953, ch. 334, § 2, 67 Stat. 389; Pub. L. 87–781, title I, §§ 105(a), (b), (d)–(f), 106(a), (b), Oct. 10, 1962, 76 Stat. 785, 786, 787; Pub. L. 90–399, § 105(b),

July 13, 1968, 82 Stat. 352; Pub. L. 102–300, § 6(b)(2),

June 16, 1992, 106 Stat. 240; Pub. L. 103–80, § 3(p), Aug. 13, 1993, 107 Stat. 777, related to certification of drugs containing penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any other antibiotic drug, prior to repeal by Pub. L. 105–115, title I, § 125(b)(1), Nov. 21, 1997, 111 Stat. 2325.

Amendments

2019—Subsec. (c)(3). Pub. L. 116–22 designated existing provisions as subpar. (A), inserted heading and “or directing” after “authorizing” in text, substituted “disclose—” for “disclose”, designated remainder of existing provisions as cl. (i) of subpar. (A), substituted “;or” for period at end, and added cl. (ii) of subpar. (A) and subpar. (B).

Statutory Notes and Related Subsidiaries

Guidance Pub. L. 114–255, div. A, title III, § 3011(b), Dec. 13, 2016, 130 Stat. 1089, provided that: “(1) In general.—The Secretary of Health and Human Services (referred to in this section [this note] as the ‘Secretary’) shall, in consultation with biomedical research consortia (as defined in subsection (e) of section 507 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 357] (as added by subsection (a)) and other interested parties through a collaborative public process, issue guidance to implement such section 507 that—“(A) provides a conceptual framework describing appropriate standards and scientific approaches to support the development of biomarkers delineated under the taxonomy established under paragraph (3); “(B) with respect to the qualification process under such section 507—“(i) describes the requirements that entities seeking to qualify a drug development tool under such section shall observe when engaging in such process; “(ii) outlines reasonable timeframes for the Secretary’s review of letters, qualification plans, or full qualification packages submitted under such process; and “(iii) establishes a process by which such entities or the Secretary may consult with biomedical research consortia and other individuals and entities with expert knowledge and insights that may assist the Secretary in the review of qualification plans and full qualification submissions under such section; and “(C) includes such other information as the Secretary determines appropriate. “(2) Timing.—Not later than 3 years after the date of the enactment of this Act [Dec. 13, 2016], the Secretary shall issue draft guidance under paragraph (1) on the implementation of section 507 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 357] (as added by subsection (a)). The Secretary shall issue final guidance on the implementation of such section not later than 6 months after the date on which the comment period for the draft guidance closes. “(3) Taxonomy.—“(A) In general.—For purposes of informing guidance under this subsection, the Secretary shall, in consultation with biomedical research consortia and other interested parties through a collaborative public process, establish a taxonomy for the classification of biomarkers (and related scientific concepts) for use in drug development. “(B) Public availability.—Not later than 2 years after the date of the enactment of this Act, the Secretary shall make such taxonomy publicly available in draft form for public comment. The Secretary shall finalize the taxonomy not later than 1 year after the close of the public comment period.”

§357 Qualification of Drug Development Tools