Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review: FDA’s expedited programs explained

Four programs, three different kinds of help

Headlines often treat “fast-tracked”, “breakthrough” and “priority review” as interchangeable. They are not. Two of the programs are designations that change how FDA works with a sponsor while a drug is still being developed (Fast Track and Breakthrough Therapy). One changes how long FDA aims to take to review a finished application (Priority Review). The fourth changes what kind of evidence can support approval in the first place (Accelerated Approval).

All four are limited to drugs and biologics for serious conditions, and a single product can collect several of them over its life. A Breakthrough Therapy designation early in development, a Priority Review at submission and an Accelerated Approval at the end is a common sequence in oncology.

Fast Track: more contact, rolling submission

Fast Track is available when a drug is intended for a serious condition and could fill an unmet medical need, either because no therapy exists or because it may offer an advantage over what is available, such as better effectiveness, avoidance of serious side effects or improved diagnosis.

A sponsor can ask for it with the investigational new drug (IND) application or at any point afterwards, and FDA decides within 60 days. The practical benefits are more frequent meetings and written feedback on the development plan, and rolling review: completed sections of the NDA or BLA can be submitted for review before the whole application is finished. A Fast Track product may also qualify for Accelerated Approval and Priority Review if it meets those programs’ own criteria.

Breakthrough Therapy: early evidence of a large improvement

Breakthrough Therapy sets a higher bar. FDA needs preliminary clinical evidence that the drug may demonstrate substantial improvement over available therapy on one or more clinically significant endpoints. That can mean an effect on irreversible morbidity or mortality, on serious symptoms, or a markedly better safety profile.

Because the designation is about shaping development, FDA asks sponsors to request it no later than the end-of-phase-2 meeting and does not expect requests after the original NDA or BLA has been submitted. FDA responds within 60 days and can also suggest the designation itself. The designation brings every Fast Track feature plus intensive guidance on an efficient development program, beginning as early as Phase 1, with commitment from senior FDA managers.

Accelerated Approval: approval on a surrogate, with strings attached

Accelerated Approval lets FDA approve a drug for a serious condition based on a surrogate endpoint (a laboratory value, image or physical sign thought to predict clinical benefit, such as tumor shrinkage) or on an intermediate clinical endpoint that is reasonably likely to predict benefit. It exists because waiting for survival or other final outcomes can take years.

The trade-off is that the sponsor must run confirmatory trials. If they verify the benefit, FDA generally ends the requirement; if they do not, or show a smaller or shorter benefit than expected, FDA can withdraw the approval or change the labeled indication.

The Food and Drug Omnibus Reform Act of 2022 (FDORA) strengthened these obligations. FDA can now require confirmatory studies to be underway before approval or within a set time afterwards, can require progress reports about every 180 days, and has an expedited procedure to withdraw an approval when the sponsor does not conduct the required studies with due diligence or when they fail to verify benefit. FDA described how it intends to apply these authorities in its December 2024 draft guidance, “Expedited Program for Serious Conditions — Accelerated Approval of Drugs and Biologics”.

Priority Review: a shorter clock, the same standard

Priority Review applies to applications for drugs that would significantly improve the safety or effectiveness of the treatment, diagnosis or prevention of a serious condition. FDA lists four kinds of evidence: increased effectiveness, elimination or substantial reduction of a treatment-limiting reaction, better patient compliance expected to improve serious outcomes, and evidence of safety and effectiveness in a new subpopulation.

FDA’s goal is to act on a priority application within 6 months, compared with 10 months under standard review, and it tells the applicant within 60 days of receipt whether the designation applies. FDA is explicit that Priority Review does not alter the scientific or medical standard for approval or the quality of evidence required.

One detail explains many “why is the decision date so late?” questions: for new molecular entities and original biologics reviewed under the PDUFA program, the review goal is counted from the end of the 60-day filing period. In practice that puts a priority decision about eight months, and a standard one about twelve months, after submission.

RMAT: the regenerative-medicine counterpart

The 21st Century Cures Act added a fifth designation, Regenerative Medicine Advanced Therapy (RMAT). It covers regenerative medicine therapies, such as cell therapies, intended to treat, modify, reverse or cure a serious condition when preliminary clinical evidence indicates the potential to address an unmet medical need. RMAT carries the Fast Track and Breakthrough Therapy features, including early interaction with FDA.

Reading designation news without overreading it

• A designation is not an approval. Many designated products never reach the market.
• FDA generally does not publish product-by-product lists of Fast Track or Breakthrough designations, so most public information comes from the sponsor’s own announcement. Check the date and the exact indication named.
• A PDUFA “target action date” is a goal date, not a promise of approval. The outcome can be an approval or a complete response letter.
• Accelerated Approval indications can change later. Check the current label on Drugs@FDA rather than the original press release.

Following expedited products on PharmaRadar360

The approvals and pipeline views collect regulator records and company announcements in one place, and drug profiles connect a product’s trials, approvals and regulatory updates. Our guide to checking a drug’s approval status explains which official database to open for each regulator.