This guidance provides recommendations to industry on when and how to identify and characterize drug metabolites whose nonclinical toxicity needs to be evaluated. The safety of drug metabolites may need to be determined in nonclinical studies because these metabolites are either identified only in humans or are present at disproportionately higher levels in humans than in any of the animal species used during standard nonclinical toxicology testing.

This guidance applies to small molecule nonbiologic drug products. This guidance does not apply to some cancer therapies where a risk-benefit assessment is considered.

This guidance supersedes the guidance of the same name published in February 2008. The guidance has been revised to be in alignment with the ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.

Posted on the FDA website on 22 November 2016