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.

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.