21 U.S.C. § 356 — Expedited approval of drugs for serious or life-threatening diseases or conditions

(a) Designation of a drug as a breakthrough therapy. If a drug's sponsor asks, the Secretary must speed up the drug's development and review when the drug treats a serious or life-threatening disease (alone or with other drugs) and early clinical evidence suggests it might work much better than existing treatments on an important measure, such as strong effects seen early in testing. This is called a "breakthrough therapy." The sponsor can ask for this designation at the same time as, or any time after, filing to test the drug in humans. The Secretary has 60 calendar days after the request to decide if the drug qualifies. If it does, the Secretary must designate it a breakthrough therapy and take appropriate steps to speed up development and review, which can include: meeting with the sponsor and review team throughout development; giving fast, interactive advice on gathering the needed data efficiently; bringing in senior managers and experienced staff for a joint, cross-disciplinary review; assigning one FDA project lead to coordinate the review and serve as the main scientific contact for the sponsor; and designing clinical trials to be as efficient as scientifically appropriate, including by limiting how many patients get a less effective treatment. (b) Designation of drug as fast track product. At the sponsor's request, the Secretary must help develop and speed up review of a new drug if it treats a serious or life-threatening disease and shows potential to meet a medical need that isn't currently met, or if the Secretary has already designated it a "qualified infectious disease product." This is called a "fast track product." The sponsor may request this designation at the same time as, or any time after, filing to test the drug in humans. Within 60 calendar days of the request, the Secretary must decide if the drug qualifies. If so, the Secretary designates it a fast track product and takes appropriate steps to speed up development and review. (c) Accelerated approval of a drug for a serious or life-threatening disease or condition, including a fast track product. The Secretary may approve a product for a serious or life-threatening disease — including a fast track product — based on an effect on a "surrogate endpoint" (a stand-in measurement reasonably likely to predict real clinical benefit), or on a clinical measurement that comes earlier than irreversible harm or death but is reasonably likely to predict an effect on it. The Secretary must weigh how severe, rare, or common the condition is and whether alternative treatments exist. This is called "accelerated approval." Evidence that an endpoint is reasonably likely to predict clinical benefit can include epidemiological, biological, treatment-related, drug-action, or other scientific evidence, such as evidence built on biomarkers. Limitation: approval under this subsection may require one or both of: (i) that the sponsor run an appropriate postapproval study to verify and describe the predicted effect on irreversible harm, death, or other clinical benefit; and (ii) that the sponsor submit all promotional materials for the product for review — during the preapproval period, and afterward, for a period the Secretary sets, at least 30 days before using them. If the Secretary doesn't require a postapproval study, the Secretary must publish on the FDA's website the reason such a study isn't appropriate or necessary. By the date of approval, the Secretary must specify the conditions for any required postapproval study or studies, which may include enrollment targets, the study protocol, and milestones such as a target completion date. The Secretary may also require a study to be underway before approval, or within a specified time after approval. Expedited withdrawal of approval: the Secretary may withdraw accelerated approval using expedited procedures if: (i) the sponsor isn't diligently conducting a required postapproval study, including as to conditions the Secretary specified; (ii) a required study fails to verify and describe the predicted effect on irreversible harm, death, or other clinical benefit; (iii) other evidence shows the product isn't shown to be safe or effective as used; or (iv) the sponsor disseminates false or misleading promotional materials about the product. Before withdrawing, the Secretary must use expedited procedures consisting of: giving the sponsor due notice, an explanation for the proposed withdrawal, a chance to meet with the Commissioner or the Commissioner's designee, and a chance for written appeal to the Commissioner or to a designee who didn't participate in the proposed withdrawal (other than that meeting) and isn't subordinate to anyone besides the Commissioner who did participate; giving the public a chance to comment on the proposed withdrawal; publishing a summary of public comments and the Secretary's responses on the FDA's website; and, if the sponsor requests it and no advisory committee has already advised the Secretary on the issue, convening and consulting an advisory committee. (d) Review of incomplete applications for approval of a fast track product. If, after a preliminary look at clinical data the sponsor submitted, the Secretary determines a fast track product may be effective, the Secretary must evaluate for filing — and may begin reviewing parts of — an application before it's complete, but only if the applicant provides a schedule for completing it and pays any required fee under section 379h. Any FDA review-time goals tied to user fees don't apply to that application until it's complete. (e) Construction. Congress intended recent amendments to this section (from the Food and Drug Administration Safety and Innovation Act and the 21st Century Cures Act) to push the Secretary toward innovative, flexible approaches to assessing accelerated-approval products for patients with serious or life-threatening conditions and unmet medical needs. Nothing in this section changes the legal standards of evidence for approval under section 355(c) or (d) — including the substantial evidence standard — or for licensure under the Public Health Service Act; those standards still govern review and approval, including whether a product is safe and effective. Nothing here stops the Secretary from relying on evidence that isn't from adequate, well-controlled studies solely to decide whether an endpoint is reasonably likely to predict clinical benefit. (f) Awareness efforts. The Secretary must: develop and share with physicians, patient organizations, drug and biotech companies, and other appropriate people a description of this section's provisions on breakthrough therapies, accelerated approval, and fast track products; and set up a program to encourage development of surrogate and clinical endpoints, biomarkers, and other scientific tools that help the Secretary judge whether submitted evidence is reasonably likely to predict clinical benefit for serious or life-threatening conditions with significant unmet medical needs. (g) Regenerative advanced therapy. At a sponsor's request, the Secretary must facilitate an efficient development program for, and expedite review of, a drug that qualifies as a "regenerative advanced therapy." To qualify, the drug must: (A) be a regenerative medicine therapy as defined in paragraph (8); (B) be intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and (C) have preliminary clinical evidence indicating it could address an unmet medical need for that condition. The sponsor may request this designation at the same time as, or any time after, filing to test the drug in humans. Within 60 calendar days, the Secretary must decide if the drug meets the criteria; if it does, the Secretary designates it and takes appropriate speed-up actions, including early interactions on any surrogate or intermediate endpoint that might support accelerated approval under subsection (c). If the drug doesn't qualify, the Secretary must include a written explanation of that determination. These sponsors are eligible for the same expedited actions as breakthrough therapies under subsection (a)(3)(B). Applications for regenerative advanced therapies may be eligible for priority review, and for accelerated approval under subsection (c), as agreed under subsection (a)(3)(B), using surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit, or data from a meaningful number of sites (including added sites). Sponsors of a regenerative advanced therapy granted accelerated approval may, as the Secretary allows, satisfy postapproval requirements under subsection (c) through: clinical evidence, clinical studies, patient registries, or other real-world evidence like electronic health records; larger confirmatory data sets agreed under subsection (a)(3)(B); or postapproval monitoring of all patients treated with the therapy before its approval. Definition: "regenerative medicine therapy" includes cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any of these — except products regulated solely under section 361 of the Public Health Service Act and 21 C.F.R. part 1271. (h) Limited population pathway for antibacterial and antifungal drugs. The Secretary may approve an antibacterial or antifungal drug as a "limited population drug" only if: (A) it's intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs; (B) the normal approval standards under section 355(c) and (d), or licensure standards under the Public Health Service Act, are met; and (C) the Secretary gets a written request from the sponsor to approve it this way. The Secretary's safety-and-effectiveness determination must reflect the drug's benefit-risk profile in that intended limited population specifically — considering how severe, rare, or common the infection is and whether alternative treatments exist in that population — and the drug can be approved even without full evidence of a favorable benefit-risk profile in a broader population. Drugs approved this way face extra requirements: labeling must show "Limited Population" prominently next to (and no more prominent than) the drug's proprietary name, or if none, its established or proper name, and the prescribing information must state the drug is "indicated for use in a limited and specific population of patients"; and the sponsor must submit all promotional materials to the Secretary at least 30 calendar days before using them. A sponsor may also seek designation or approval of the same drug under other applicable sections of this chapter or the Public Health Service Act. Not later than 18 months after December 13, 2016, the Secretary had to issue draft guidance on demonstrating safety and effectiveness for these drugs, and final guidance within 18 months after the comment period on that draft closed; the Secretary may approve drugs under this pathway before that guidance issues. The Secretary must give sponsors prompt advice for planning a development program, including any additional studies needed for approval in a broader population. If the drug later gets approved for a broader indication, the Secretary may remove the postmarketing conditions (like labeling and promotional-material review) tied to the limited approval. Nothing in this subsection changes the Secretary's authority to approve drugs, the standards of evidence for approval, or the authority to monitor drugs under this chapter or the Public Health Service Act. Reporting and accountability: the Secretary must report to Congress at least every two years on the number of requests and approvals under this pathway; and by December 2021, the Comptroller General had to report to the House Energy and Commerce Committee and Senate HELP Committee on the coordination of related activities, reviewing whether the pathway has streamlined approval, worked as intended, helped patients, should extend to other drug categories, and affected antibacterial or antifungal resistance.