Applications and Regulatory Acceptance of PBPK Modeling

Model informed drug development (also called biosimulation) has had a sizeable impact on drug development, both in supporting R&D decision-making and in regulatory acceptance. Physiologically based pharmacokinetics (PBPK) modeling has shifted that paradigm forward and is actively encouraged by global regulators, with specific applications and capabilities highlighted in scores of published papers, presentations and acceptances in drug labels. PBPK is a biosimulation methodology that mechanistically describes the behavior of drugs in different body tissues, with each tissue considered a physiological compartment. The concentration of the drug in each compartment is determined by combining systems data, drug data, and trial design information.

During this session, we will share the recent history of PBPK and its application for determining first-in-human dosing, optimizing clinical study design, evaluating new drug formulations, setting the dose in untested populations, predicting dosing for special populations, including different ages, ethnicities, and co-morbidities, performing virtual bioequivalence analyses, and predicting drug-drug interactions (DDIs)—in small molecules, biologics, ADCs, generics, and new modality drugs. We will identify several key case studies that validate the power of the technology. A current landscape of acceptances in 2022 will be discussed, as will a view toward the future for PBPK.