The Use of Physiologically Based Pharmacokinetic Analyses-in Biopharmaceutics Applications -Regulatory and Industry Perspectives

Abstract

The use of physiologically based pharmacokinetic (PBPK) modeling to support the drug product quality attributes, also known as physiologically based biopharmaceutics modeling (PBBM) is an evolving field and the interest in using PBBM is increasing. The US-FDA has emphasized on the use of patient centric quality standards and clinically relevant drug product specifications over the years. Establishing an in vitro in vivo link is an important step towards achieving the goal of patient centric quality standard. Such a link can aid in constructing a bioequivalence safe space and establishing clinically relevant drug product specifications. PBBM is an important tool to construct a safe space which can be used during the drug product development and lifecycle management. There are several advantages of using the PBBM approach, though there are also a few challenges, both with in vitro methods and in vivo understanding of drug absorption and disposition, that preclude using this approach and therefore further improvements are needed. In this review we have provided an overview of experience gained so far and the current perspective from regulatory and industry point of view. Collaboration between scientists from regulatory, industry and academic fields can further help to advance this field and deliver on promises that PBBM can offer towards establishing patient centric quality standards.

Keywords: PBBM; PBPK; biopharmaceutics; clinically relevant dissolution; critical bioavailability attributes; critical quality attributes.