21 U.S.C. § 356
The Secretary shall, at the request of the sponsor of a drug, expedite the development and review of such drug if the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. (In this section, such a drug is referred to as a "breakthrough therapy".)
The sponsor of a drug may request the Secretary to designate the drug as a breakthrough therapy. A request for the designation may be made concurrently with, or at any time after, the submission of an application for the investigation of the drug 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)] .
Not later than 60 calendar days after the receipt of a request under paragraph (2), the Secretary shall determine whether the drug that is the subject of the request meets the criteria described in paragraph (1). If the Secretary finds that the drug meets the criteria, the Secretary shall designate the drug as a breakthrough therapy and shall take such actions as are appropriate to expedite the development and review of the application for approval of such drug.
The actions to expedite the development and review of an application under subparagraph (A) may include, as appropriate-
The Secretary shall, at the request of the sponsor of a new drug, facilitate the development and expedite the review of such drug if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition, or if the Secretary designates the drug as a qualified infectious disease product under section 355f(d) of this title. (In this section, such a drug is referred to as a "fast track product".)
The sponsor of a new drug may request the Secretary to designate the drug as a fast track product. A request for the designation may be made concurrently with, or at any time after, submission of an application for the investigation of the drug 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)] .
Within 60 calendar days after the receipt of a request under paragraph (2), the Secretary shall determine whether the drug that is the subject of the request meets the criteria described in paragraph (1). If the Secretary finds that the drug meets the criteria, the Secretary shall designate the drug as a fast track product and shall take such actions as are appropriate to expedite the development and review of the application for approval of such product.
The Secretary may approve an application for approval of a product for a serious or life-threatening disease or condition, including a fast track product, under section 355(c) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. The approval described in the preceding sentence is referred to in this section as "accelerated approval".
The evidence to support that an endpoint is reasonably likely to predict clinical benefit under subparagraph (A) may include epidemiological, pathophysiological, therapeutic, pharmacologic, or other evidence developed using biomarkers, for example, or other scientific methods or tools.
Approval of a product under this subsection may be subject to 1 or both of the following requirements:
If the Secretary does not require that the sponsor of a product approved under accelerated approval conduct a postapproval study under this paragraph, the Secretary shall publish on the website of the Food and Drug Administration the rationale for why such study is not appropriate or necessary.
Not later than the date of approval of a product under accelerated approval, the Secretary shall specify the conditions for a postapproval study or studies required to be conducted under this paragraph with respect to such product, which may include enrollment targets, the study protocol, and milestones, including the target date of study completion.
The Secretary may require, as appropriate, a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.
The Secretary may withdraw approval of a product approved under accelerated approval using expedited procedures described in subparagraph (B) if-
Expedited procedures described in this subparagraph shall consist of, prior to the withdrawal of accelerated approval-
If 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-
Any time period for review of human drug applications that has been agreed to by the Secretary and that has been set forth in goals identified in letters of the Secretary (relating to the use of fees collected under section 379h of this title to expedite the drug development process and the review of human drug applications) shall not apply to an application submitted under paragraph (1) until the date on which the application is complete.
The amendments made by the Food and Drug Administration Safety and Innovation Act and the 21st Century Cures Act to this section are intended to encourage the Secretary to utilize innovative and flexible approaches to the assessment of products under accelerated approval for treatments for patients with serious or life-threatening diseases or conditions and unmet medical needs.
Nothing in this section shall be construed to alter the standards of evidence under subsection (c) or (d) of section 355 of this title (including the substantial evidence standard in section 355(d) of this title) or under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] . Such sections and standards of evidence apply to the review and approval of products under this section, including whether a product is safe and effective. Nothing in this section alters the ability of the Secretary to rely on evidence that does not come from adequate and well-controlled investigations for the purpose of determining whether an endpoint is reasonably likely to predict clinical benefit as described in subsection (b)(1)(B).
The Secretary shall-
The Secretary, at the request of the sponsor of a drug, shall facilitate an efficient development program for, and expedite review of, such drug if the drug qualifies as a regenerative advanced therapy under the criteria described in paragraph (2).
A drug is eligible for designation as a regenerative advanced therapy under this subsection if-
The sponsor of a drug may request the Secretary to designate the drug as a regenerative advanced therapy concurrently with, or at any time after, submission of an application for the investigation of the drug 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)] .
Not later than 60 calendar days after the receipt of a request under paragraph (3), the Secretary shall determine whether the drug that is the subject of the request meets the criteria described in paragraph (2). If the Secretary determines that the drug meets the criteria, the Secretary shall designate the drug as a regenerative advanced therapy and shall take such actions as are appropriate under paragraph (1). If the Secretary determines that a drug does not meet the criteria for such designation, the Secretary shall include with the determination a written description of the rationale for such determination.
The sponsor of a regenerative advanced therapy shall be eligible for the actions to expedite development and review of such therapy under subsection (a)(3)(B), including early interactions to discuss any potential surrogate or intermediate endpoint to be used to support the accelerated approval of an application for the product under subsection (c).
An 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-
The 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-
For purposes of this section, the term "regenerative medicine therapy" includes cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under section 361 of the Public Health Service Act [42 U.S.C. 264] and part 1271 of title 21, Code of Federal Regulations.
The 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-
The Secretary's determination of safety and effectiveness of an antibacterial or antifungal drug shall reflect the benefit-risk profile of such drug in the intended limited population, taking into account the severity, rarity, or prevalence of the infection the drug is intended to treat and the availability or lack of alternative treatment in such limited population. Such drug may be approved under this subsection notwithstanding a lack of evidence to fully establish a favorable benefit-risk profile in a population that is broader than the intended limited population.
A drug approved under this subsection shall be subject to the following requirements, in addition to any other applicable requirements of this chapter:
To indicate that the safety and effectiveness of a drug approved under this subsection has been demonstrated only with respect to a limited population-
The sponsor of an antibacterial or antifungal drug subject to this subsection shall submit to the Secretary copies of all promotional materials related to such drug at least 30 calendar days prior to dissemination of the materials.
A sponsor of a drug that seeks approval of a drug under this subsection may also seek designation or approval, as applicable, of such drug under other applicable sections or subsections of this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.].
Not later than 18 months after December 13, 2016, the Secretary shall issue draft guidance describing criteria, processes, and other general considerations for demonstrating the safety and effectiveness of limited population antibacterial and antifungal drugs. The Secretary shall publish final guidance within 18 months of the close of the public comment period on such draft guidance. The Secretary may approve antibacterial and antifungal drugs under this subsection prior to issuing guidance under this paragraph.
The Secretary shall provide prompt advice to the sponsor of a drug for which the sponsor seeks approval under this subsection to enable the sponsor to plan a development program to obtain the necessary data for such approval, and to conduct any additional studies that would be required to gain approval of such drug for use in a broader population.
If, after approval of a drug under this subsection, the Secretary approves a broader indication for such drug under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)], the Secretary may remove any postmarketing conditions, including requirements with respect to labeling and review of promotional materials under paragraph (3), applicable to the approval of the drug under this subsection.
Nothing in this subsection shall be construed to 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], including the standards of evidence and applicable conditions for approval under such chapter or Act, the standards of approval of a drug under such chapter or Act, or to alter the authority of the Secretary to monitor drugs pursuant to such chapter or Act.
The Secretary shall report to Congress not less often than once every 2 years on the number of requests for approval, and the number of approvals, of an antibacterial or antifungal drug under this subsection.
Not later than December 2021, the Comptroller General of the United States 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 on the coordination of activities required under section 319E of the Public Health Service Act [42 U.S.C. 247d-5] . Such report shall include a review of such activities, and the extent to which the use of the pathway established under this subsection has streamlined premarket approval for antibacterial or antifungal drugs for limited populations, if such pathway has functioned as intended, if such pathway has helped provide for safe and effective treatment for patients, if such premarket approval would be appropriate for other categories of drugs, and if the authorities under this subsection have affected antibacterial or antifungal resistance.
1So in original.
21 U.S.C. § 356
EDITORIAL NOTES
REFERENCES IN TEXTThe Food and Drug Administration Safety and Innovation Act, referred to in subsec. (e)(1), is Pub. 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 Pub. L. 114-255. For the amendments made to this section by the Act, see 2016 Amendment notes below.Section 101(b) of the Prescription Drug User Fee Amendments of 2012, referred to in subsec. (g)(6)(A), is section 101(b) of Pub. 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 PROVISIONSA prior section 356, act June 25, 1938, ch. 675, §506, as added Dec. 22, 1941, ch. 613, §3, 55 Stat. 851; amended Pub. L. 102-300, §6(b)(2), June 16, 1992, 106 Stat. 240; Pub. L. 103-80, §3(o), Aug. 13, 1993, 107 Stat. 777, related to certification of drugs containing insulin, prior to repeal by Pub. L. 105-115, title I, §125(a)(1), Nov. 21, 1997, 111 Stat. 2325.
AMENDMENTS2022-Subsec. (c)(2). Pub. L. 117-328, §3210(a)(1)(A), (B), (D), designated existing provisions as subpar. (A), inserted heading, 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). Pub. L. 117-328, §3210(a)(1)(C), substituted "an appropriate postapproval study or studies" for "appropriate postapproval studies". Subsec. (c)(3). Pub. L. 117-328, §3210(a)(2)(B), (C), (F), designated existing provisions as subpar. (A), inserted heading, redesignated former subpars. (A) to (D) as cls. (i) to (iv), respectively, of subpar. (A) and realigned margins, and added subpar. (B). Pub. 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). Pub. 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). Pub. L. 117-328, §3210(a)(2)(E), inserted "shown to be" after "product is not". 2016-Subsec. (e). Pub. L. 114-255, §3033(a)(1), transferred subsec. (e) to appear before subsec. (f).Subsec. (e)(1). Pub. L. 114-255, §3033(c), inserted "and the 21st Century Cures Act" after "Food and Drug Administration Safety and Innovation Act". Subsec. (g). Pub. L. 114-255, §3033(a)(2), added subsec. (g).Subsec. (h). Pub. L. 114-255, §3042, added subsec. (h).2012- Pub. L. 112-144, §901(b), 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). Pub. L. 112-144, §902(a)(3), added subsec. (a). Former subsec. (a) redesignated (b).Subsec. (a)(1). Pub. L. 112-144, §803, amended subsec. (a)(1), as amended by Pub. L. 112-144, §901(b), 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. (b) to (d). Pub. L. 112-144, §902(a)(1), redesignated subsecs. (a) to (c) as (b) to (d), respectively. Former subsec. (d) relating to awareness efforts redesignated (f). Subsec. (f). Pub. 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 Pub. L. 114-255, §3033(a)(1), which transferred subsec. (e) to appear before subsec. (f) "relating to awareness efforts".Subsec. (f)(1). Pub. 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 DATESection effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Pub. L. 105-115 set out as an Effective Date of 1997 Amendment note under section 321 of this title.
CONSTRUCTION OF 2022 AMENDMENT Pub. 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 356b 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 Pub. L. 114-255, div. A, title III, §3033(b), 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." Pub. L. 114-255, div. A, title III, §30433043,, 130 Stat. 1114, provided that: "Nothing in this subtitle [subtitle E (§§3041-3044) of title III of div. A of Pub. 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 Pub. 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 Pub. L. 114-255, div. A, title III, §30353035,, 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. "(b) 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 Pub. L. 112-144, title IX, §901(a), July 9, 2012, 126 Stat. 1082, as amended by Pub. L. 114-255, div. A, title III, §3101(b)(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 Pub. 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 (b), for drugs designated for a rare disease or condition under section 526 of such Act (21 U.S.C. 360bb) 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 (b)."(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 (b) 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 (b)." Pub. L. 112-144, title IX, §902(b), 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." Pub. L. 105-115, title I, §112(b), 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."