Drugs

Follow-up Testing for Ames-Positive Drugs: Guide

FDA has posted a draft guidance entitled “Recommended Follow-Up Testing for an Ames-Positive Drug (Active Ingredient) or Metabolite To Support First-in-Human Clinical Trials With Healthy Subjects.” The document provides agency feedback on how CDER views positive findings in an in vitro bacterial reverse mutation (Ames) test of a drug (active ingredient) or its metabolites and recommendations on follow-up in vitro and in vivo mutagenicity testing of Ames-positive active ingredients to support first-in-human (FIH) clinical trials.

The agency says that typically most active ingredients found to be positive for mutagenicity (i.e., Ames-positive) are not further developed. “Due to their therapeutic mechanism of action, active ingredients used for treating oncology indications may be an exception and might be further developed for potential approval by FDA, even if they are mutagenic,” the guidance says. The document makes recommendations on follow-up testing for Ames-positive active ingredients in those rare circumstances when a sponsor decides to continue development. “These recommendations are intended to potentially address and lower certain safety concerns before proceeding with FIH trials in healthy human subjects.”

Additionally, FDA says that follow-up testing cannot completely erase the concerns raised by an Ames-positive finding, and some residual risk remains in the absence of an adequate carcinogenicity assessment. “Thus, Ames-positive active ingredients that are further developed should be those targeting serious or life-threatening diseases with unmet medical needs,” the guidance says. “Thus, a robust nonclinical program of studies that can help characterize potential risk to determine that it is sufficiently low is required before FIH trials can commence in healthy human subjects.”

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome