Role of Physiologically Based Pharmacokinetic Modeling and Simulation in Enabling Model-Informed Development of Drugs and Biotherapeutics.

Abstract

Model-informed drug development (MIDD) strategies and associated quantitative approaches have enhanced the design, development, and benefit-risk assessment of therapeutics. With advances in our understanding of disease biology and pathophysiology, the complexities of mechanisms of action of emerging therapeutics are steadily on the rise. Taken together with the growing diversity of therapeutic modalities ranging from traditional small molecules to complex genetically engineered cell therapies, clinical use of contemporary therapies demands commitment to integrative “systems” approaches that iteratively exploit the totality of drug-, disease-, and population-level knowledge to guide objective decisions. The inclusion of MIDD-related performance goals in the Prescription Drug Use Fee Act VI is a strong testament to the interest and commitment around the use of novel methodologies to facilitate the conduct of efficient clinical trials. The need for a holistic approach to advance the vision of MIDD and the impact of MIDD-based approaches on dose optimization, informing clinical trial design and providing supportive evidence of efficacy, has also been discussed. 1,2