Preparing for safety issues following drug approval: pre-approval risk management considerations.

Risk management plans and risk minimization plans as well as postapproval commitment studies are based on risks identified pre-approval that need to be further characterized or minimized in the postmarketing environment. Although the implementation of these activities are conducted in the postapproval arena, the design of the plans and studies as well as the development of effective postapproval tools and mitigation strategies should be carried out pre-approval. The pre-approval period also provides the opportunity to fully understand the treatment population that is included in the clinical trial program and to determine how the target population for the drug after approval may differ from the clinical trial patient population. When regulators or sponsors have expressed concerns about safety issues identified during clinical development, the result may be a postapproval commitment in the form of a registry or an observational safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval. Specific examples are given for risk mitigation activities that can be conducted pre-approval.