Physiologically based pharmacokinetic modeling in regulatory decision‐making at the European Medicines Agency

TLDR

Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, enabling mechanistic simulation of a compound’s pharmacokinetics across diverse populations and scenarios. This study aims to review the use and impact of PBPK modeling in regulatory procedures submitted to the EMA before 2015. The authors examined selected EMA submissions and subsequent public documents to assess how PBPK modeling was referenced and reflected in regulatory assessments. The analysis shows that PBPK modeling is underrepresented in regulatory documents, yet its use has increased over time and, in several cases, influenced decision‑making or labeling recommendations, underscoring the need for EMA guidance in this area.

Abstract

Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision-making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.