REGULATORY GUIDELINES ON THE REPORTING OF PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING ANALYSIS

According to Food and Drug Administration (FDA), physiologically based pharmacokinetic (PBPK) model predictions can be used throughout a drug's life cycle, to support decisions on whether, when, and how to conduct certain clinical pharmacology studies and to support dosing recommendations in product labeling. The European Medicines Agency (EMA) guideline “Guideline on the reporting of physiologically based pharmacokinetic (PBPK) modeling and simulation” came into effect on 1 July 2019. The guidelines called for PBPK platform qualification for an intended use with well-characterized in vivo data as well as an evaluation of the predictive performance of the specific drug model. For model development, EMA requires a quantitative mass-balance diagram while FDA does not. Several features of the risk-informed evidentiary framework are similar to that proposed by the EMA guidelines for PBPK reporting. PBPK model verification for locally acting products is challenged by the difficulty to measure active site drug concentrations for comparison with model predicted exposure.