Consideration of a Credibility Assessment Framework in Model‐Informed Drug Development: Potential Application to Physiologically‐Based Pharmacokinetic Modeling and Simulation

TLDR

Computational models in drug development have expanded, yet no consensus exists on how to establish credibility for regulatory decision‑making. The authors propose a risk‑informed credibility assessment framework for physiologically‑based pharmacokinetic modeling and simulation, aiming to spark discussion and promote a uniform regulatory evaluation across MIDD approaches. They apply the framework by evaluating verification and validation activities specific to PBPK models within a risk‑informed structure.

Abstract

The use of computational models in drug development has grown during the past decade. These model‐informed drug development (MIDD) approaches can inform a variety of drug development and regulatory decisions. When used for regulatory decision making, it is important to establish that the model is credible for its intended use. Currently, there is no consensus on how to establish and assess model credibility, including the selection of appropriate verification and validation activities. In this article, we apply a risk‐informed credibility assessment framework to physiologically‐based pharmacokinetic modeling and simulation and hypothesize this evidentiary framework may also be useful for evaluating other MIDD approaches. We seek to stimulate a scientific discussion around this framework as a potential starting point for uniform assessment of model credibility across MIDD. Ultimately, an overarching framework may help to standardize regulatory evaluation across therapeutic products (i.e., drugs and medical devices).