PI-109 - IMPACT OF RISK EVALUATION AND MITIGATION STRATEGY PROGRAMS ON PRODUCT-SPECIFIC GUIDANCES FOR GENERIC DRUG DEVELOPMENT

A. Moore^1,2, K. Li³, J. Shon³, M. Kim³, S. Borges³, D. Nguyen³; ¹Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA, ²Division of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA, ³U.S. Food and Drug Administration, Silver Spring, MD, USA.

Background: The U.S. Food and Drug Administration’s approvals of certain drug products require risk evaluation and mitigation strategy (REMS) programs to ensure their benefits outweigh their risks. Product-specific guidances (PSGs) of REMS-covered reference listed drug (RLD) products generally contain a standard recommendation for generic drug applicants to incorporate all pertinent REMS elements into the protocol to ensure subject safety in pharmacokinetic (PK) bioequivalence (BE) studies. REMS may be modified post-approval; thus, there is a need to continually review approved REMS programs. This project aimed to investigate the current status of REMS recommendations in PSGs.

Methods: We compiled a list of approved REMS programs and of PSGs containing REMS recommendations for oral drug products. The data were collected from the public REMS and PSG databases and analyzed: types of risks requiring REMS, modifications to the REMS programs, PSG availability, and REMS-related and other relevant PSG recommendations.

Results: As of July 2024, there were 38 approved REMS programs for oral drug products. The most common types of risks covered by these programs were: embryo-fetal toxicity (n=14); overdose, abuse, misuse, addiction (n=6); and cardiotoxicity (n=6). Of the 73 available associated PSGs, we identified 42 PSGs with up-to-date standard REMS recommendations. The remaining 31 PSGs were identified to not align with the respective REMS programs and their modification history based on: relief of REMS requirements (5 PSGs), update of REMS program name (1 PSG), and lack of standard REMS recommendations for REMS-covered RLD products (25 PSGs). Of note, in these 25 PSGs, their additional comments conveyed specific risk-mitigating recommendations through exclusion criteria, coadministration with an antagonist, and/or monitoring parameters. Most PSGs recommended PK BE studies in healthy subjects (59 of 73 PSGs) or using the highest strength available (53 of 73 PSGs).

Conclusion: The current project demonstrated that the impact of REMS programs on PSG recommendations varied depending on the type of risk covered and intended study population. Continual review of approved REMS is needed to ensure up-to-date recommendations and alleviate requirements during the conduct of PK BE studies, thereby facilitating generic drug development and availability.