Risk management of drug products and the U.S. Food and Drug Administration: evolution and context.

This paper summarizes the background and origins of pharmaceutical risk management and minimization principles and approaches as reflected in FDA statute, policy, and practice. It describes the history of early "risk management" programs, such as the patient package inserts (PPIs) introduced for oral contraceptives in 1976 and medication guides developed for products with safety concerns over the past decade. Exemplary products and programs that include restricted distribution systems such as the early clozapine "blood for drug" program are discussed. The principles and tools described in the US Food and Drug Administration (FDA) risk management guidances of 2005 are likely to be relied upon as the REMS (Risk Evaluation and Mitigation Strategies) mandated by the FDA Amendments Act (FDAAA) of 2007 are implemented.