Role of Physiologically Based Modeling and Simulations in Clinical Pharmacokinetic Study Waivers for Orally Administered Drug Products

The pharmaceutical industry's drug development process, from discovery to post-marketing surveillance, has evolved significantly with the advent of Model-Informed Drug Development.These models, which simulate drug behavior in the body using physiological parameters, are crucial for predicting drug interactions, optimizing dosing, and assessing various factors impacting drug exposure.Physiologically based pharmacokinetic models streamline drug development by reducing the need for extensive clinical trials, thus accelerating the approval process.In the generic drug sector, these models are instrumental in achieving bioequivalence and expediting market access.By offering a predictive framework, physiologically based pharmacokinetic modeling ensures that generic drugs meet regulatory standards efficiently, ultimately enhancing the affordability and accessibility of essential medicines.These models support biowaiver justification, scale-up and post-approval changes, and evaluation of critical bioavailability attributes.This review summarizes physiologically based pharmacokinetic models applications in obtaining clinical pharmacokinetic study waivers, emphasizing dissolution data incorporation and detailing a workflow for model development, validation, and application.Additionally, it highlights literature reports and case studies where physiologically based pharmacokinetic models and physiologically based biopharmaceutics models were used for biowaivers, dissolution mismatch, formulation impact, and safety evaluations, showcasing their broad utility in drug development.