Examination of risk evaluation and mitigation strategies and drug safety in the US.

BACKGROUND: The Food and Drug Administration Amendment Act of 2007 (FDAAA 2007) enabled the US Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) for a drug or biologic to ensure that its benefits outweigh the risks.

OBJECTIVE: This study sought to evaluate REMS approved and released by the FDA since the program inception in 2008, to assess the characteristics of REMS approved and to calculate the time lag between FDA drug application approval and REMS approval.

METHODS: Data were derived from Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Data included generic availability, application type and approval date, therapeutic class and FDA review class, orphan designation, priority review and market status.

RESULTS: The FDA approved REMS for 259 marketing applications (217 new drug applications -NDAs, 10 abbreviated NDAs, and 32 biologic license applications) in the study period. The FDA granted orphan designation to 11.4% of active ingredients with REMS and priority review to 38.4% of the NDAs with REMS. The largest number of REMS approvals was for nervous system products (31.8% of total approved REMS) and antineoplastic and immunomodulating agents (15.3%).

CONCLUSIONS: The FDA approved REMS for one in three biologics and one in thirteen chemical entities available in the market. A pharmaceutical product can be in the market for an average of 14 years before the FDA identifies and evaluates the risk problems that warrant the approval of a REMS.