Metabolite bioanalysis has been the subject of discussion in many conferences over the past couple of decades. These discussions initially led to the FDA guidelines for Metabolites In Safety Testing (MIST) in 2008, followed by the ICH M3 (R2) in 2009. Recently, the FDA updated its MIST guidance to align with ICH M3 (R2). The MIST guidance provides the agency’s expectations with respect to metabolite characterization and exposure assessment. However, it does not provide guidance on the level of rigor needed for the quality of the assays used for metabolite bioanalysis and lacks guidance on which stage of drug development metabolite bioanalysis is needed or which studies are in scope. The FDA guidance on bioanalytical method validation allows a fit-for-purpose approach for metabolite bioanalysis for ex-vivo samples providing flexibility in using a tiered approach in metabolite bioanalysis. However, the industry still struggles with the level of qualification/validation that is needed at different stages of drug development. Recently, the FDA guidance on ‘In Vitro Drug Interaction Studies-Cytochrome P450 Enzyme and Transporter Mediated Drug Interactions’, added to this lack of clarity by calling for “validated” methods for in vitro assays. Many have asked for further clarity on the use of “validated” methods. In this session we hope to provide substrate for a robust discussion on when metabolite bioanalysis is needed, the level of assay qualification required differentiating between ex-vivo and in vitro samples, the studies that are in scope.
This presentation will help set the stage for the hot topic discussion on metabolite bioanalysis and the decision on which metabolites need to be characterized from a PK perspective and whether their analysis is needed in every clinical study.
The presentation will discuss the regulatory guidelines related to metabolite bioanalysis (directly or indirectly) and the rigor of method qualification/validation required.
It will discuss the difference between metabolite bioanalysis and metabolite identification and in vitro metabolite characterization.
Further, it will, we expect, provide substrate for a robust discussion on when the methods for metabolite bioanalysis and in vitro studies need to be validated and the rigor of the validation.
Provides a case study to showcase when metabolite bioanalysis is needed during the course of drug development.