FDA Expedited Programs: Fast Track, Breakthrough, Accelerated Approval

Several FDA programs get called "fast track" in conversation. Fast Track and Breakthrough Therapy change how FDA works with you during development, Accelerated Approval changes the evidence you may use, and Priority Review changes the review clock.

Each is granted separately, and one product can hold several.

Fast Track

For a drug treating a serious condition where non-clinical or clinical data suggest it addresses an unmet medical need.

It provides more meetings and more written communication with the review division, and eligibility to submit completed portions of the application as they are ready rather than all at once, which is rolling review.

It does not lower the evidence standard and does not shorten the review clock. Its value is that problems surface in a meeting rather than in a Complete Response Letter.

Breakthrough Therapy

Also for a serious condition, but the bar is higher: preliminary clinical evidence indicating substantial improvement over available therapy on a clinically significant endpoint.

Everything Fast Track offers, plus intensive guidance on efficient development starting as early as Phase 1, and an organizational commitment involving senior FDA managers. In return, FDA is closely involved in your development plan.

Accelerated Approval

Accelerated approval lets FDA approve a drug for a serious condition on a surrogate endpoint, or on an intermediate clinical endpoint, rather than waiting for the clinical outcome itself. A surrogate endpoint is a laboratory measure or physical sign reasonably likely to predict clinical benefit.

Confirmatory trials are mandatory. Since FDORA in 2022, FDA can require that the confirmatory trial is already underway at the time of accelerated approval, sponsors report progress, and FDA has simplified authority to withdraw the approval when a confirmatory trial fails or is not completed with due diligence.

FDA could not enforce the confirmatory obligation this way before 2023.

Priority Review

Priority review sets FDA's goal at six months from the filing date instead of ten, for a drug that would be a significant improvement in safety or effectiveness.

A priority review application meets the same evidence standard on a shorter timetable.

Priority review vouchers, awarded under programs such as rare pediatric disease, are a separate mechanism: a transferable right to priority review of a future application, which can be sold.

Orphan Drug Designation, which is not an expedited program

Orphan designation is often listed alongside these and works differently. It is granted for a drug treating a rare disease or condition, defined as affecting fewer than 200,000 people in the US.

It provides development incentives rather than a faster or easier review: tax credits for qualified clinical testing, a waiver of the application user fee, and seven years of marketing exclusivity for the designated indication on approval.

The exclusivity runs independently of patents. Orphan designation does not guarantee approval.

Choosing between them

The requests are cheap relative to a development program. A typical sequence:

1. Orphan designation as early as the prevalence case supports it.
2. Fast Track with or shortly after the IND, on the serious-condition and unmet-need argument.
3. Breakthrough once you have preliminary clinical evidence, if it is strong enough to argue substantial improvement.
4. Accelerated approval discussed at end-of-Phase-2, with the confirmatory trial designed at the same time, not afterwards.
5. Priority review requested with the application.

The real decision is accelerated approval, because it commits you to a confirmatory trial you must be able to fund and enrol. The others add access and optionality.