Accelerated Approval

Accelerated Approval is one of FDA’s four main expedited programs for drugs and biologics treating serious or life-threatening conditions, alongside Priority Review, Breakthrough Therapy designation, and Fast Track. Unlike the other three, which speed up development or FDA’s review clock while the evidence itself stays conventional, Accelerated Approval changes what evidence FDA will accept for approval in the first place: an effect on a surrogate endpoint reasonably likely to predict clinical benefit, rather than a demonstrated clinical benefit itself.

Regulatory basis

The pathway is authorized under 21 CFR Part 314 Subpart H (drugs, 21 CFR 314.500-314.560) and 21 CFR Part 601 Subpart E (biologics, 21 CFR 601.40-601.46). Under 21 CFR 314.510 and 601.41, FDA may approve a product for a serious or life-threatening illness based on adequate and well-controlled trials establishing that the product has an effect on a surrogate endpoint — or on a clinical endpoint that itself falls short of irreversible morbidity or mortality (an intermediate clinical endpoint) — that is reasonably likely to predict clinical benefit. In making that determination, FDA can weigh epidemiologic, therapeutic, pathophysiologic, or other evidence supporting the surrogate’s biological plausibility, not only direct trial data on the surrogate itself.

Eligibility criteria

• The product treats a serious or life-threatening condition.
• The product provides a meaningful therapeutic advantage over available therapy (or addresses an unmet medical need where no adequate therapy exists).
• The supporting evidence rests on an effect on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit — a lower evidentiary bar than a validated surrogate endpoint, which can support approval without any further confirmatory requirement.

The confirmatory trial requirement

Accelerated Approval is conditional, not final. The sponsor must conduct a post-approval confirmatory trial designed to verify that the predicted clinical benefit is real. Historically, sponsors could obtain accelerated approval with a confirmatory trial only committed to, not yet enrolling — a gap an HHS Office of Inspector General report (September 2022) highlighted, finding more than a third of accelerated approvals had incomplete confirmatory trials, over a third of which had already passed their planned completion date.

The Food and Drug Omnibus Reform Act of 2022 (FDORA), enacted December 29, 2022 as part of the Consolidated Appropriations Act, 2023, closed that gap. FDORA gives FDA explicit authority to require that a confirmatory trial be underway at the time of approval, or within a specified period afterward, rather than simply promised. FDA’s December 2024 and January 2025 draft guidance documents on Accelerated Approval requirements and processes further describe what ‘underway’ means in practice and how sponsors should plan confirmatory-trial timing relative to the marketing application.

Expedited withdrawal

FDORA also created specific expedited procedures FDA can use to withdraw an Accelerated Approval, including where a required confirmatory trial fails to verify the predicted clinical benefit, or where other evidence shows the product is not safe or effective under its labeled conditions of use. The expedited process still preserves core due-process steps — notice and an explanation of the proposed withdrawal, an opportunity for a meeting with the Commissioner or a designee, a written appeal, public comment, and, if requested (and not already addressed by a prior advisory committee), an advisory committee meeting — but is materially faster than the withdrawal process that applied before 2022. FDA has since used the FDORA authority to withdraw at least one accelerated approval, a notable break from the years-long withdrawal timelines that were common historically.

Two 2026 worked examples

Two approvals a day apart in August 2026 show the pathway’s range: one a conventional oncology accelerated approval on tumor-response endpoints, the other an unusual split approval on a vaccine.

Tudriqev (vusolimogene oderparepvec-wtpg) — the textbook oncology case

On August 6, 2026, FDA granted accelerated approval to Tudriqev (Replimune, Inc.), a genetically modified oncolytic viral therapy, in combination with nivolumab for adults with unresectable advanced cutaneous melanoma who experienced disease progression on a PD-1-blocking antibody-based regimen. The approval rested on objective response rate and duration of response — not survival — measured in IGNYTE (NCT03767348), an open-label, single-arm trial of 140 patients, of whom the 91 with at least one non-injected lesion formed the efficacy-evaluable population. ORR was 24.2% (15.8, 34.3) and median DOR 14.1 months (10.7, not reached). Replimune is required to conduct post-approval trial(s) to verify and describe clinical benefit, and continued approval may be contingent on that verification. The combination also held Breakthrough Therapy designation — a concrete instance of the stacking described below, since Breakthrough Therapy and Accelerated Approval are granted on separate criteria and neither implies the other.

Mflusiva (Influenza Vaccine, mRNA) — a split, partial accelerated approval

On August 5, 2026, FDA licensed Mflusiva (ModernaTX, Inc.; BLA 125869) for active immunization against influenza in persons 50 years of age and older. What makes it instructive is that only part of the indication is an accelerated approval: FDA’s approval letter states that “the indication for persons 65 years of age and older is approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and the regulations for accelerated approval, 21 CFR 601.41” — the biologics citation given above — while the 50-to-64 age band was approved on conventional terms. The surrogate endpoint for the older band was immune response, with clinical benefit defined by FDA as “demonstration of effectiveness against influenza disease in adults 65 years of age and older.” A pathway can therefore attach to a subset of an indication and leave the rest on the ordinary standard.

The confirmatory obligation here is a named, scheduled postmarketing requirement rather than an open-ended promise: study mRNA-1010-P910, a pragmatic randomized study of relative vaccine effectiveness against a high-dose influenza vaccine in U.S. adults 65 years of age and older, carrying FDA-specified milestones including study initiation by August 31, 2026 and final report submission by May 31, 2030. That dated initiation milestone is the FDORA “underway, not merely promised” requirement made operational, and the approval letter states plainly that if the study fails to verify clinical benefit or is not conducted with due diligence, FDA may withdraw the approval. Two administrative consequences are worth noting: progress must be reported in 180-day reports (two per year for each open required study, under FDCA section 506B(a)(2)), and, uniquely to accelerated approval, promotional materials are subject to pre-clearance under 21 CFR 601.45.

How it differs from the other three expedited programs

Fast Track and Breakthrough Therapy designation are development-phase designations: a sponsor requests them, typically well before an application is filed, to unlock more frequent FDA interaction, rolling review, and (for Breakthrough Therapy) intensive FDA guidance on an efficient development program. Priority Review is a review-timeline classification FDA assigns to a completed marketing application, shortening its review-clock goal from 10 months to 6. Accelerated Approval is different in kind from all three: it is the one pathway that changes the evidentiary standard for approval itself, substituting a surrogate or intermediate endpoint for direct proof of clinical benefit — which is exactly why it, uniquely among the four, carries a binding post-approval confirmatory-trial obligation and a withdrawal mechanism if that obligation isn’t met. A single product can carry more than one of these four designations simultaneously; they aren’t mutually exclusive.

Why it matters for research administrators

For sponsors and CROs, an Accelerated Approval commitment is not the end of a trial’s regulatory obligations — it converts into a defined, FDA-monitored post-marketing study obligation with its own budget, timeline, and reporting requirements, and, since FDORA, its own enrollment-timing pressure. For research-administration and clinical-trials-office staff supporting an accelerated-approval program, tracking the confirmatory trial’s status against its committed timeline is now a compliance matter with real regulatory consequences, not just a scientific follow-up.

Frequently Asked Questions

What is a surrogate endpoint, and why does FDA accept it for accelerated approval?

A surrogate endpoint is a measure — such as a lab value or tumor-response measurement — that is reasonably likely to predict a real clinical benefit, even though it is not the clinical benefit itself (like survival or how a patient feels or functions). Under 21 CFR 314.510 and 601.41, FDA can accept an effect on such an endpoint as the basis for accelerated approval of a product for a serious or life-threatening condition, drawing on epidemiologic, therapeutic, and pathophysiologic evidence to judge the surrogate’s biological plausibility.

How is accelerated approval different from Priority Review, Fast Track, and Breakthrough Therapy designation?

Fast Track and Breakthrough Therapy are development-phase designations that give a sponsor more frequent FDA interaction and guidance while the evidence generated stays conventional, and Priority Review simply shortens FDA’s review-clock goal for a completed application from 10 months to 6. Accelerated Approval is different in kind: it is the one pathway that changes the evidentiary standard for approval itself, substituting an effect on a surrogate or intermediate endpoint for direct proof of clinical benefit — which is why it alone carries a binding post-approval confirmatory-trial obligation.

What happens if the required confirmatory trial fails to confirm the drug’s benefit?

FDA can withdraw the accelerated approval. The Food and Drug Omnibus Reform Act of 2022 (FDORA) created expedited withdrawal procedures FDA can use where a confirmatory trial fails to verify the predicted clinical benefit, or where other evidence shows the product isn’t safe or effective as labeled — while still preserving core due-process steps like notice, a hearing opportunity, and public comment. FDA has already used this authority to withdraw at least one accelerated approval.

Does the confirmatory trial have to already be underway before FDA grants accelerated approval?

Historically it did not — sponsors could receive accelerated approval with a confirmatory trial only committed to, not yet enrolling, which an HHS Office of Inspector General report found had left more than a third of accelerated approvals with incomplete confirmatory trials. FDORA closed that gap by giving FDA explicit authority to require the trial be underway at approval, or within a specified period afterward, rather than merely promised.

Can a product hold both Breakthrough Therapy designation and accelerated approval at the same time?

Yes. The two are granted on separate criteria and neither implies the other, but a single product can carry more than one of FDA’s four expedited-program designations simultaneously since they aren’t mutually exclusive. Tudriqev’s 2026 approval for advanced cutaneous melanoma is one example: it carried both Breakthrough Therapy designation and accelerated approval based on objective response rate and duration of response.

Can accelerated approval apply to only part of a drug’s approved indication?

Yes. Mflusiva’s 2026 licensure illustrates this: FDA approved the indication for adults 65 and older under accelerated approval, based on immune response as the surrogate endpoint, while the 50-to-64 age band within the same approval was licensed on conventional terms. A single marketing approval can therefore mix an accelerated-approval indication with a conventionally approved one.