Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision‐making—A workshop summary

In industry, the application of PBPK occurs throughout drug development in a continuous learn and confirm cycle, including assessing risk during the discovery phase, characterizing the drug’s clinical pharmacology properties, and addressing labeling requirements in late phases. 2 Data from PBPK modeling can be included as part of a regulatory submission for certain areas of application, as illustrated by a PBPK model that helped characterize the drug interaction potential of abemaciclib and informed the label. FDA’S PROPOSED FRAMEWORK FOR CREDIBILITY ASSESSMENT Colleen Kuemmel (FDA) highlighted the agency’s white paper titled “Consideration of a Credibility Assessment Framework in Model-Informed Drug Development: Potential Application to Physiologically Based Pharmacokinetic Modeling and Simulation,” 5 which describes the application of an evidentiary framework to assess PBPK model credibility, that could standardize terminology and may offer a uniform approach to model evaluation. Of note, it requires a team of experts to apply the framework and assess the adequacy of the model The question-and-answer panel discussion was moderated by Ping Zhao (Bill & Melinda Gates Foundation), who engaged with Colleen Kuemmel and panelists Susan Cole (UK Medicines and Healthcare products Regulatory Agency), Tina Morrison (FDA), Million Tegenge (FDA), Yuching Yang (FDA), and Liang Zhao (FDA) to gain insight into the applicability of the framework during drug development and regulatory review. By examining the structural model, the spike vanished if concentrations in the PBPK model were sampled from a peripheral venous sampling site rather than an arterial site. [...]a sampling location discrepancy between the model and observed samples appeared to account for the difference between the observed and predicted data.