Many of my clients contact me stating, “we wish to pursue an accelerated pathway,” or “we need to submit an application for priority status for a breakthrough product to treat an unmet need.” These words are commonly used in a single breath with confusion around the meaning of these terms. It can be overwhelming to drug developers on what requirements are involved for their appropriate development pathway. For regulators, these phrases have very specific meanings, and it’s important that sponsors understand the options available to them and when one might apply to their program.
Navigating the regulatory drug development pathway is already complex, especially for those trying to advance research for serious conditions. Speed to market, in such cases, is not only a desire of an applicant for their investigational agent, but also the goal of the Food and Drug Administration (FDA), especially for novel approaches or advancements over available therapies. The FDA has developed specific pathways to address a more rapid clinical development and review process to gain faster access of therapies for patients with serious conditions. Understanding the regulatory vocabulary is fundamental and a solid first step.
Summary of important terminology:
Serious Condition: defines a disease or condition associated with morbidity that has substantial impact on day-to-day functioning.
Unmet Need: defines a therapy where none/limited exists, or a therapy which may be potentially better than available therapy to treat a serious condition for a defined population
Available Therapy: an approved or licensed product in the U.S. for the same indication and is relevant to current standard of care.
Orphan Status: a separate designation requested by a sponsor through a formal application process to the FDA Office of Orphan Products Development (OOPD). Not all serious conditions qualify as an orphan drug. Orphan status is reserved for rare conditions that must affect less than 200,000 persons in the U.S. or meets cost recovery provisions.
Priority Review: designated (can also be requested by applicants formally) by an FDA review division at the time of the Biologic Licensing Application (BLA), New Drug Application (NDA), or efficacy supplement filing, and grants sponsors a six-month marketing application review clock; it is assigned over other applications if the product is thought to have significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition.
Accelerated Approval: provides a pathway in study designs where a clinically significant advantage is anticipated over available therapy by demonstrating a meaningful effect on a surrogate endpoint - an endpoint which is likely to predict a positive clinical benefit.
Fast Track Designation: a formal application by a sponsor to an FDA division at any time during the development process (including preclinical) to encourage early and frequent interactions. If granted, the sponsor gains access to the FDA with increased communications on their development plan. The FDA may also grant Priority Review and Accelerated Approval for treatments of serious conditions that fulfill an unmet medical need (as defined above); examples include showing superiority, a better safety profile over available therapies, or an advancement in a public health need. Fast Track Designation allow for rolling reviews, permitting sections of an NDA or BLA to be submitted for review to FDA as they are ready, rather than all at once.
Breakthrough Therapy: grants sponsors guidance and commitments at senior levels and all the potential benefits of Fast Track Designation. This must be requested by the sponsor or recommended by the FDA no later than the End of Phase 2 meeting. The program must show preliminary clinical evidence over current therapies with clinically significant endpoints (efficacy and/or safety) for serious conditions.
The FDA has published information clarifying these pathways, each having success in getting therapies to market in shorter timeframes. Specific details to each process designed to expedite the development and review of drugs is available through Guidance for Industry documents and on the FDA’s website: https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review.
By getting the right lingo down, sponsors can have meaningful discussions with the agency on their research and data in hopes of reaching patients with serious conditions in shorter timeframes.
Understanding these pathways to pursue your investigational research and the timing of when to partner with the FDA are an important part of navigating the regulatory pathway. When defining each aspect of this research, independent third-party guidance can help your team navigate the challenge of knowing which next steps to take. This support can help you plan and execute your next clinical program for serious conditions.
- Guidance for Industry, Expedited Programs for Serious Conditions – Drugs and Biologics. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologic Evaluation and Research (CBER); May 2014,
- Guidance for Industry, Fast Track Drug Development Programs-Designation, Development, and Application Review. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologic Evaluation and Research (CBER); September 1998.
- 21 CFR part 314, subpart H
- 21 CFR part 601, subpart E
- Food Drug and Cosmetic Act, Section 506(b) and 506(c)
- Prescription Drug User Fee Act of 1992
About the Author: Norma Ascroft, Pharm.D. is a Managing Expert for YourEncore’s Regulatory Center of Excellence. Norma specializes in strategic planning and execution of clinical-regulatory programs of investigational and new drug applications for life science companies, including leading cross-functional teams through FDA negotiations and interactions pre- and post-marketing.
For additional questions and to learn more about the YourEncore Regulatory Center of Excellence, contact a Managing Expert or visit our website at https://www.yourencore.com/.