Chapter 38 – Regulatory Perspectives

The efficient identification and characterization of risk for clinically serious drug-induced liver injury (DILI) associated with newly developed pharmaceuticals and biological agents are important objectives for regulatory science. In the United States, the implementation of consistent analytic and risk management approaches with a recently expanded set of regulatory tools is expected to have a positive public health benefit. Cellular and molecular mechanisms that underlie DILI must be more fully elucidated in order to develop reliable biomarkers that will accurately predict which new drugs are destined to cause clinically serious DILI, identify those patients who are at increased risk, or forecast progression from mild to serious organ injury. Both consistent monitoring practices and comprehensive clinical evaluation of patients with liver injury during clinical trials are required to estimate DILI risk in a large treatment population. Moreover, thorough analyses of idiosyncratic DILI cases in spontaneous reports and postmarketing clinical studies play a critical role in risk assessment. Finally, optimal product labeling, as well as effective risk communication and management, should reflect cumulative risk-related data and overall product-associated benefit and risk considerations.