Expedited Programs Beyond Orphan Designation

Tina Wang • May 11, 2026

When developing a drug for a rare disease, orphan drug designation is often the first regulatory milestone on the list. But it is not the only incentive the FDA has created to help promising therapies reach patients faster. For sponsors navigating the complex landscape of drug development, understanding the full scope of FDA expedited programs is an important part of building a successful regulatory strategy.

At Only Orphans Cote, we work directly with drug sponsors to navigate FDA and EMA regulatory requirements, from data assessment through submission. Under the leadership of Dr. Timothy Cote, former Director of the FDA's Office of Orphan Product Development, our team brings firsthand regulatory experience to every client engagement. Dr. Cote personally decided on 1,400 orphan designation applications and wrote about 900 orphan designations as a consultant.

Submissions for Expedited Programs is one of the core services we offer. Beyond orphan designation, there are four FDA programs designed to accelerate drug development and approval for serious conditions with unmet medical needs. Understanding these programs, and whether your drug may qualify for one or more of them, can meaningfully shape your development timeline.

Four Expedited Drug Approval Programs

Not all drug approvals follow the FDA's standard review process. Drug therapies that address unmet medical needs, treat serious or life-threatening conditions, or show a significant advantage over current therapies may be eligible for one or more of the FDA's four expedited review programs. These programs are designed to accelerate the approval process and make therapies available to patients more quickly, provided that the benefits justify the risks. The four programs are Priority Review, Accelerated Approval, Fast Track, and Breakthrough Therapy.

1. Priority Review

Priority Review shortens the FDA's standard review timeline from 10 months to 6 months. To be eligible, a drug must treat a serious condition and provide a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of that condition compared to existing treatments.

Drug sponsors request Priority Review at the time of submitting either a New Drug Application (NDA) or a Biologics License Application (BLA). There is also a second route: Priority Review Vouchers. These vouchers are awarded to sponsors who develop treatments for neglected tropical diseases and rare pediatric diseases, can be redeemed by the sponsor or sold to another sponsor to use for the same purpose.

2. Accelerated Approval

The Accelerated Approval pathway allows the FDA to approve a drug based on a surrogate endpoint or intermediate endpoint, rather than waiting for traditional primary clinical outcomes such as overall survival or progression-free survival. Surrogate endpoints can include lab values, imaging results, physical signs, or other scientifically accepted measures, and serve as a proxy for clinical benefit. Because it often takes years for primary endpoints to mature, this pathway allows promising drugs to reach patients sooner.

To qualify, a drug must treat a serious condition, provide a meaningful advantage over available therapies, and demonstrate a surrogate endpoint reasonably likely to predict clinical benefit. Sponsors typically explore the possibility of Accelerated Approval with the FDA early in the development process, often during the design of clinical trials. As a condition of approval, sponsors are required to complete post-marketing confirmatory trials to verify the predicted clinical benefit. If post-marketing studies don't verify the efficacy of the drug, approval can be revoked at the discretion of the FDA.

3. Fast Track Designation

Fast Track designation improves the efficiency of the drug development and review process by enabling rolling review. Under a standard submission, the FDA requires all segments of an NDA or BLA to be submitted before review begins. With Fast Track, the FDA can review portions of the application as they arrive, rather than waiting for the complete package. The program also facilitates more frequent communication between the drug sponsor and FDA reviewers during development, which can help address questions earlier and reduce delays.

Eligible drugs must treat a serious condition, and nonclinical or clinical data must demonstrate the potential to address an unmet medical need. In 2022, 32% of novel new drugs approved by the FDA's Center for Drug Evaluation and Research (CDER) had received Fast Track designation.

4. Breakthrough Therapy

Breakthrough Therapy designation is typically reserved for drugs treating life-threatening or debilitating disease states where preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapies on a clinically significant endpoint. To be eligible, a drug must treat a serious condition and have substantial improvement on a clinically significant endpoint(s) over available therapies.

Breakthrough Therapy includes all of the benefits of Fast Track designation, plus organizational commitment from FDA senior managers to engage in intensive guidance throughout the clinical development process.

“You get extra love from the FDA,” as Timothy Cote puts it. Fast Track can be pursued with an open IND, making it an earlier and more accessible opportunity to engage the FDA and facilitate development. Breakthrough Therapy designation, by contrast, requires preliminary clinical evidence and a higher evidentiary bar. It is more subjective, selective and often more impactful, but also more difficult to obtain.

In practice, Fast Track is a valuable and strategic first step, while Breakthrough represents a more advanced designation with greater upside once sufficient data are available.

What Are the Benefits of Expedited Programs?

The four expedited programs share a common purpose: helping innovative drugs for serious unmet needs reach patients faster. A review published in the Journal of Personalized Medicine (Kantor and Haga, 2021) analyzed all FDA-approved new molecular entities (NMEs) between 2011 and 2017 and found that the majority of approved NMEs were associated with at least one expedited approval or FDA review pathway. Understanding both the advantages and the limitations of these programs is valuable for any sponsor building a regulatory strategy.

The Benefits

The most direct benefit is speed. Across the 250 NMEs approved between 2011 and 2017, Priority Review was the most commonly used program (applied to 133 drugs), while Accelerated Approval was the least common (applied to 32). The study found that expedited pathways were associated with faster times to approval, particularly in oncology, where companies frequently combined more than one expedited strategy.

Expedited programs also tend to attract more innovative therapies. More than one-third of all NMEs approved during the study period were first-in-class agents. The average number of expedited development programs per first-in-class drug reached 2.23, compared to 1.61 across all NMEs, suggesting that the most novel therapies benefit disproportionately from these mechanisms. The proportion of Breakthrough Therapy designation among first-in-class drugs was also higher than the overall rate.

Beyond speed, some programs offer structural development advantages. Breakthrough Therapy designation allows submission based on earlier phase trial data. Fast Track and Breakthrough Therapy both enable rolling review, reducing the bottleneck of a complete submission requirement. Accelerated Approval allows drugs to reach patients before primary endpoints have fully matured. And Priority Review compresses the FDA's review clock from 10 months to 6 months.

Conclusion

The FDA's four expedited programs, Priority Review, Accelerated Approval, Fast Track, and Breakthrough Therapy, exist alongside orphan drug designation as powerful tools to help qualifying drugs move through development and review more efficiently. For sponsors working on treatments for rare and serious conditions, understanding how these programs work and whether a drug may qualify is a critical part of regulatory planning.

At Only Orphans Cote, Submissions for Expedited Programs for rare disease drugs is one of our core regulatory services. With Dr. Timothy Cote at the helm, backed by decades of firsthand FDA experience and a record of supporting over 600 clients, our team is positioned to assess your drug's eligibility and guide your application with clarity, speed, and confidence.

Ready to explore whether your drug may qualify for an expedited program? Contact us today.

FAQs

What is the difference between orphan drug designation and the four expedited programs?

Orphan drug designation applies to drugs treating conditions that affect fewer than 200,000 people in the United States, and provides benefits including a partial tax credit for clinical trial expenditures, waived user fees, and seven years of marketing exclusivity. The four expedited programs (Priority Review, Accelerated Approval, Fast Track, and Breakthrough Therapy) are focused on accelerating the development and review process for drugs treating serious conditions with unmet medical needs. A drug can qualify for orphan designation and one or more expedited programs at the same time.

Can a drug qualify for more than one expedited program?

Yes. Drugs can qualify for more than one expedited program simultaneously. The analysis of 2011 to 2017 NME approvals found that the average number of expedited development and review programs per approved drug was 1.61 overall, rising to 2.23 for first-in-class drugs.

When should a sponsor request expedited designation?

The timing depends on the program. Fast Track and Breakthrough Therapy designations are typically requested during drug development, before the NDA or BLA is submitted. Breakthrough Therapy must be requested no later than the end of Phase II clinical trial meetings with the FDA. Priority Review is requested at the time of NDA or BLA submission. Accelerated Approval is typically explored early in the development process, often during the design of clinical trials.

What is a surrogate endpoint for Accelerated Approval purposes?

A surrogate endpoint is a measure used in clinical trials that is reasonably likely to predict a drug's clinical benefit, even though it does not directly measure patient outcomes like survival. Examples include lab values, imaging results, physical signs, and other scientifically accepted measures. Using a surrogate endpoint allows approval to proceed before full primary outcome data have matured.

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Accelerate Your Orphan Drug Strategy

Only Orphans Cote helps sponsors secure orphan drug designation faster. Contact us today to schedule a consultation with Dr. Tim Cote and our team.

Orphan Drug Designation by the European Medicines Agency (EMA ODD)

By Tina Wang • May 22, 2026

Learn how to obtain EMA orphan drug designation, how it differs from FDA ODD, and how Only Orphans Cote helps biotechs win EU rare disease approvals.

A Win for Rare Pediatric Disease Drug Innovation: The RPDD & PRV Program Is Reauthorized Through 2029, and OOC Is Ready

By Tina Wang • March 27, 2026

February 3, 2026 was a significant day for the rare pediatric disease community. The Consolidated Appropriations Act of 2026 was signed into law, reauthorizing the Rare Pediatric Disease Designation Priority Review Voucher (RPDD PRV) program through September 30, 2029. After a year of anxiety over the sunset, sponsors who have been building rare pediatric disease programs can once again treat PRV eligibility as a reliable planning assumption rather than an expiring hope. The window is now open, with a clear timeline, and the opportunity is significant. At Only Orphans Cote (OOC), our CEO, Dr. Timothy Cote, was one of the legislators involved in the creation of the RPDD PRV program. Here is what the reauthorization means, why it matters, and how OOC can help you act on it. What Are RPDD and PRV? Rare Pediatric Disease Designation (RPDD) is granted by the U.S. FDA to drugs intended to treat or prevent serious or life-threatening diseases that primarily affect children and affect fewer than 200,000 patients in the United States. If a drug with RPDD is ultimately approved, the sponsor may receive a Priority Review Voucher (PRV), a transferable certificate that entitles the holder to request priority FDA review for any future drug application. Importantly, the voucher can be sold to any other sponsor. This creates a secondary market where rare disease biotechs monetize their regulatory achievement, and large pharma companies purchase time-to-market advantages for their most lucrative pipelines. In practical terms, a PRV compresses the FDA review timeline from roughly ten months to about six months. That four-month acceleration is enormously valuable for large pharmaceutical companies racing to bring high-value drugs to market, which is why PRVs consistently trade in the $75 million to $150 million range, making them one of the most valuable non-dilutive assets in drug development. A Program With Deep Roots, and OOC's Fingerprints on It The PRV concept was first proposed in a landmark 2006 Health Affairs paper by Ridley, Grabowski, and Moe . Congress acted on it the following year, establishing the tropical disease PRV program in 2007 under the FDA Amendments Act (FDAAA) to incentivize treatments for neglected tropical diseases. The success of that model led policymakers to extend the mechanism to rare pediatric diseases through the FDA Safety and Innovation Act (FDASIA) of 2012, creating the RPDD PRV program we know today. The program has been reauthorized before, in 2016 and again in 2020, each time for four additional years. The 2026 reauthorization follows that same pattern, extending it to September 30, 2029. What makes OOC's perspective on this program genuinely singular is that our CEO, Dr. Timothy Cote, was one of the legislators involved in the creation of the RPDD PRV program. Dr. Cote is the former Director of the FDA Office of Orphan Products Development (OOPD), and is the only former Director of FDA/OOPD currently working as a regulatory consultant focused on orphan drug development. The Numbers Speak for Themselves The RPDD PRV program has been running for over a decade. The evidence of its impact is clear. According to an analysis from the National Organization for Rare Disorders (NORD), updated in November 2025: 63 RPDD Priority Review Vouchers have been awarded since the program's inception. 47 distinct rare pediatric diseases are represented among those approvals. 43 of those 47 diseases had no FDA-approved treatment before the PRV-earning drug was approved. That last figure is the most powerful: the program has delivered first-ever treatments to 43 rare pediatric disease communities that previously had none. This is the PRV program working exactly as intended, using commercial incentives to drive innovation where the market alone would not. How the PRV Market Actually Works The ability to sell a Priority Review Voucher creates a powerful economic engine for small and mid-sized rare pediatric biotechs. Developing therapies for rare pediatric diseases often involves small patient populations and limited commercial markets, making it extremely difficult for early-stage companies to recover development costs through product revenue alone. The PRV program addresses this by creating a secondary market for regulatory incentives. When a rare pediatric drug receives FDA approval and qualifies for a PRV, the sponsor can sell that voucher to another pharmaceutical company seeking to accelerate review of a future drug application. In practice: Vouchers have historically sold for between approximately $50 million and $350 million. Recent transactions have clustered in the $75 million to $150 million range. For the rare disease biotech, this is immediate, non-dilutive capital to reinvest in pipeline development. For the large pharma buyer, a PRV means a potential four-month head start to market on a high-value drug. For blockbuster drugs expected to generate billions in annual revenue, launching even a few months earlier can yield enormous financial returns and competitive advantages, including beating rivals to market. This creates a mutually beneficial ecosystem that has become a significant and mature financial driver across the rare disease drug development landscape. What the Consolidated Appropriations Act of 2026 Actually Does The Consolidated Appropriations Act of 2026 , signed into law on February 3, 2026, delivers an important change for the rare disease community: RPDD PRV Program Reauthorized Through September 30, 2029 The Act extends the program's sunset date, restoring certainty for any sponsor that had been building a rare pediatric disease pipeline with PRV eligibility in mind. FDA may award PRVs for qualifying drug approvals through September 30, 2029. The reauthorization also clarifies that there is no separate deadline by which a drug must receive its RPDD designation prior to the sunset date, an important technical point for sponsors whose designation timelines may span multiple years. How OOC Helps You Navigate the RPDD PRV Lifecycle Only Orphans Cote LLC is a consultancy dedicated to orphan drug development, led by Dr. Timothy Cote , one of the legislators involved in the creation of the RPDD PRV program, bringing direct policy and regulatory experience to sponsors pursuing rare disease incentives. Our work provides sponsors with the direct policy and regulatory experience needed to successfully pursue RPDD and PRV eligibility, from initial assessment through approval. We work with emerging biotechs and established pharmaceutical companies. Whether you are pursuing RPDD for the first time or repairing a previously unsuccessful submission, OOC brings unmatched regulatory and policy expertise rooted in helping shape the program itself. Let's Talk The reauthorization of the RPDD PRV program is a moment to act, not wait. While the Priority Review Voucher itself is awarded upon market approval, obtaining RPDD as early as possible is strategically crucial. The designation signals PRV potential, which can significantly strengthen fundraising and partnering discussions.The time to build your RPDD PRV strategy is now, not at approval. Dr. Cote's direct experience as one of the legislators involved in the creation of the RPDD PRV program, combined with his background as former Director of FDA/OOPD, gives OOC a depth of knowledge in this space that is available to sponsors through our team. To learn more, visit Only Orphans Cote or reach out directly to our team .