Drug Metabolite Safety Testing Guidance

FDA has published a guidance, Safety Testing of Drug Metabolites, with recommendations to industry on when and how to identify and characterize drug metabolites whose nonclinical toxicity needs to be evaluated. The document applies to small molecule nonbiologic drug products and does not apply to some cancer therapies.

FDA says that drug metabolites may need to be determined in nonclinical studies when they are disproportionate drug metabolites or metabolites identified only in humans or present at higher plasma concentrations in humans than in any of the animal species used during standard nonclinical toxicology testing.

The guidance supersedes an 11/2016 guidance. It was revised to align with an International Council for Harmonization guidance.

The contents include Introduction, Background, General Concepts in Metabolite Safety Testing, Recommended Studies for Assessing the Safety of Metabolites, Glossary, and two Appendices.