Deputy Director US FDA Washington, District of Columbia, United States
Seizures occurring in toxicology studies can derail drug development. Current approaches for detection are limited to careful monitoring and use of EEG studies to understand risk. Assays that allow earlier detection could identify compounds with greater risk; these assays could also have utility at later stages in development for human risk assessment of convulsions observed in toxicology studies and in comparing relative risk to existing therapeutic options. However, there is limited experience with these approaches for regulatory decision making. Major challenges include validating predictivity which will require identification of appropriate endpoints and thresholds of concern derived from these data, standardizing methodologies, and building the database of in vitro and in vivo data to assist in establishing exposure margins. Nonetheless, the development of new approach methodologies is supported by FDA and if in vitro studies identify risky drug candidates early in drug discovery and development they should help reduce animal use.
