21 U.S.C. § 356

(a) Designation of a drug as a breakthrough therapy (1) In general 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”.) (2) Request for designation 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) ]. (3) Designation (A) In general 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. (B) Actions The actions to expedite the development and review of an application under subparagraph (A) may include, as appropriate— (i) holding meetings with the sponsor and the review team throughout the development of the drug; (ii) providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable; (iii) involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review; (iv) assigning a cross-disciplinary project lead for the Food and Drug Administration review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor; and (v) taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment. (b) Designation of drug as fast track product (1) In general 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”.) (2) Request for designation 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) ]. (3) Designation 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. (c) Accelerated approval of a drug for a serious or life-threatening disease or condition, including a fast track product (1) In general (A) Accelerated approval 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”. (B) Evidence 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. (2) Limitation (A) In general Approval of a product under this subsection may be subject to 1 or both of the following requirements: (i) That the sponsor conduct an appropriate postapproval study or studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit. (ii) That the sponsor submit copies of all promotional materials related to the product during the preapproval review period and, following approval and for such period thereafter as the Secretary determines to be appropriate, at least 30 days prior to dissemination of the materials. (B) Studies not required 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. (C) Postapproval study conditions 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. (D) Studies begun before approval 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. (3) Expedited withdrawal of approval (A) In general The Secretary may withdraw approval of a product approved under accelerated approval using expedited procedures described in subparagraph (B) if— (i) the sponsor fails to conduct any required postapproval study of the product with due diligence, including with respect to conditions specified by the Secretary under paragraph (2)(C); (ii) a study required to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit of the product fails to verify and describe such effect or benefit; (iii) other evidence demonstrates that the product is not shown to be safe or effective under the conditions of use; or (iv) the sponsor disseminates false or misleading promotional materials with respect to the product. (B) Expedited procedures described Expedited procedures described in this subparagraph shall consist of, prior to the withdrawal of accelerated approval— (i) providing the sponsor with— (I) due notice; (II) an explanation for the proposed withdrawal; (III) an opportunity for a meeting with the Commissioner or the Commissioner’s designee; and (IV) an opportunity for written appeal to— (aa) the Commissioner; or (bb) a designee of the Commissioner who has not participated in the proposed withdrawal of approval (other than a meeting pursuant to subclause (III)) and is not subordinate of an individual (other than the Commissioner) who participated in such proposed withdrawal; (ii) providing an opportunity for public comment on the proposal to withdraw approval; (iii) the publication of a summary of the public comments received, and the Secretary’s response to such comments, on the website of the Food and Drug Administration; and (iv) convening and consulting an advisory committee on issues related to the proposed withdrawal, if requested by the sponsor and if no such advisory committee has previously advised the Secretary on such issues with respect to the withdrawal of the product prior to the sponsor’s request. (d) Review of incomplete applications for approval of a fast track product (1) In general 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— (A) provides a schedule for submission of information necessary to make the application complete; and (B) pays any fee that may be required under section 379h of this title . (2) Exception 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. (e) Construction (1) Purpose 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. (2) Construction 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). (f) Awareness efforts The Secretary shall— (1) develop and disseminate to physicians, patient organizations, pharmaceutical and biotechnology companies, and other appropriate persons a description of the provisions of this section applicable to breakthrough therapies, accelerated approval, and and 1 1 So in original. fast track products; and (2) establish a program to encourage the development of surrogate and clinical endpoints, including biomarkers, and other scientific methods and tools that can assist the Secretary in determining whether the evidence submitted in an application is reasonably likely to predict clinical benefit for serious or life-threatening conditions for which significant unmet medical needs exist. (g) Regenerative advanced therapy (1) In general 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). (2) Criteria A drug is eligible for designation as a regenerative advanced therapy under this subsection if— (A) the drug is a regenerative medicine therapy (as defined in paragraph (8)); (B) the drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and (C) preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such a disease or condition. (3) Request for designation 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) ]. (4) Designation 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. (5) Actions 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). (6) Access to expedited approval pathways 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— (A) eligible for priority review, as described in the Manual of Policies and Procedures of the Food and Drug Administration and goals identified in the letters described in section 101(b) of the Prescription Drug User Fee Amendments of 2012; and (B) eligible for accelerated approval under subsection (c), as agreed upon pursuant to subsection (a)(3)(B), through, as appropriate— (i) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit; or (ii) reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites, as appropriate. (7) Postapproval requirements 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— (A) the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records; (B) the collection of larger confirmatory data sets, as agreed upon pursuant to subsection (a)(3)(B); or (C) postapproval monitoring of all patients treated with such therapy prior to approval of the therapy. (8) Definition 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. (h) Limited population pathway for antibacterial and antifungal drugs (1) In general 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— (A) the drug is intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs; (B) the standards for approval under section 355(c) and (d) of this title, or the standards for licensure under section 351 of the Public Health Service Act [ 42 U.S.C. 262 ], as applicable, are met; and (C) the Secretary receives a written request from the sponsor to approve the drug as a limited population drug pursuant to this subsection. (2) Benefit-risk consideration 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. (3) Additional requirements A drug approved under this subsection shall be subject to the following requirements, in addition to any other applicable requirements of this chapter: (A) Labeling To indicate that the safety and effectiveness of a drug approved under this subsection has been demonstrated only with respect to a limited population— (i) all labeling and advertising of an antibacterial or antifungal drug approved under this subsection shall contain the statement “Limited Population” in a prominent manner and adjacent to, and not more prominent than— (I) the proprietary name of such drug, if any; or (II) if there is no proprietary name, the established name of the drug, if any, as defined in section 353(e)(3) of this title , or, in the case of a drug that is a biological product, the proper name, as defined by regulation; and (ii) the prescribing information for the drug required by section 201.57 of title 21, Code of Federal Regulations (or any successor regulation) shall also include the following statement: “This drug is indicated for use in a limited and specific population of patients.”. (B) Promotional material 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. (4) Other programs 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.]. (5) Guidance 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. (6) Advice 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. (7) Termination of limitations 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. (8) Rules of construction 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. (9) Reporting and accountability (A) Biennial reporting 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. (B) GAO report 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.