Safety Testing of Drug Metabolites: A Practical Approach for the Implementation of the MIST Guidance in PKDM

Abstract

The FDA Safety Testing of Drug Metabolites Guidance and the ICH Requirements for Registration of Pharmaceuticals for Human Use (ICH M3) guidance defined threshholds for metabolite exposure in humans and preclinical species, which (ICH M3) would indicate that preclinical species were exposed adequately to quantitatively significant human metabolites. Proactive, data‐driven, best practices were developed by consensus with key development partners. Nontraditional metabolism approaches such as nonradiometric high resolution‐mass spectrometry (HR‐MS) profiling of plasma metabolites across species were developed to enable timely drug development decision making.