For sponsors developing innovative drugs and biological products, understanding the regulatory programs available to expedite development and approval is important.
The United States Food and Drug Administration (FDA) has four programs that are designed to expedite development and review of new drugs to address unmet medical needs in the treatment of serious or life-threatening conditions: fast track designation, breakthrough therapy designation (breakthrough designation), priority review, and accelerated approval.
Both fast track and breakthrough designation are designed to speed up drug development. Priority review shortens FDA review time of a New Drug Application (NDA) or a Biologics License Application (BLA). Accelerated approval is an abbreviated approval pathway. The programs have different qualifying criteria and administrative processes and, for qualifying products, may be used in conjunction with each other to minimize the time and expense of bringing a drug or biological product to market.
Fast track designation
Fast track designation is intended to facilitate the development and expedite the review of drugs that treat serious conditions and fill unmet medical needs. Designation may be granted on the basis of preclinical data.
A sponsor of a drug that receives fast track designation will typically have more frequent interactions with FDA during drug development. In addition, products that have been designated as fast track can obtain rolling review, which means that a drug company can submit
completed sections of its NDA or BLA for review by FDA, rather than waiting until every section of the application is completed before the entire application can be submitted and reviewed.
Similar to fast track designation, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. However, unlike fast track designation which may be granted on the basis of preclinical data, the criteria for breakthrough designation require preliminary clinical evidence that demonstrates that the drug may achieve a substantial improvement on at least one clinically significant endpoint over available therapy.
A breakthrough designation conveys all benefits of the fast track program. In addition, such a designation conveys more intensive FDA guidance on an efficient drug development program, including an organizational commitment involving senior FDA managers (an “all hands on deck” approach).
Drugs that have received breakthrough designation have seen their stock increase, sometimes substantially. See, e.g., C. Werble,Breakthrough Math: Alexion Gains $400 Million on Asfotase Breakthrough Designation, Pharma & MedTech Business Intelligence (29 May 2013). Presumably, such a designation signals to investors that the product may be approved after a shorter and less expensive drug development period.
As part of its commitments in the most recent reauthorization of the Prescription Drug User Fee Act (PDUFA V), FDA has established a review model, which it calls “the Program.” The Program applies to all new molecular entity NDAs and original BLAs, including applications that are resubmitted following a Refuse-to-File action, received from 1 October 2012 through 30 September 2017. For applications filed by FDA under the Program, the PDUFA review clock will begin at the conclusion of the 60 calendar day filing review period that begins on the date of FDA receipt of the original submission.
Priority review shortens FDA review time from 10 months to six months. This review designation is determined at the time of a BLA, NDA, or efficacy supplement submission. Any drug, including those that have received a fast track designation, breakthrough therapy designation, or those being evaluated for accelerated approval, can be granted priority review, if the relevant criteria are met.
For many drugs and biologics that treat serious and life-threatening diseases, showing actual improvement for patients, such as increased longevity or reduced morbidity, can take a prolonged period of time. Consequently, FDA promulgated the accelerated approval regulation, which allows earlier approval of drugs and biologics based on a surrogate clinical endpoint. For example, tumor progression and time to tumor shrinkage may be used as surrogate endpoints for oncology drugs in certain situations.
Using surrogate endpoints instead of clinical outcome data can significantly reduce the time required to receive marketing approval for a compound.
In addition, accelerated approval shortens the actual research time prior to approval. For example, instead of two adequate and well-controlled studies, a sponsor who is granted accelerated approval might only have to conduct one of these studies prior to FDA approval.
It is important to note that accelerated approval can be granted with restrictions, such as:
- being limited to prescription by specially trained physicians only, if necessary for safe use of the drug; or
- with distribution being made conditional on performance of specified medical procedures.
In addition, per FDA draft guidance recommendations, products approved under the accelerated approval pathway on the basis of a specific surrogate or clinical endpoint should state so in the product’s labeling. The labeling should also state that continued approval may be contingent upon verification or demonstration of clinical benefit in a post-marketing study. Such caveats in labeling statements could make practitioners and consumers wary of using accelerated approval products because such statements could be misinterpreted to mean that the products have not met the statutory requirements of safety and efficacy required of all FDA-approved drugs.
Together, these four expedited programs under U.S. law offer sponsors a variety of regulatory tools to help facilitate and expedite regulatory approvals and access for patients to innovative therapies.