ICH Mutagenic Impurities Drug Guidance

FDA has released an International Council for Harmonization-developed guidance entitled “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.” The document is intended to provide a “practical framework” for identifying, categorizing, qualifying and controlling mutagenic impurities to limit potential carcinogenic risk. It “emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk,” according to the agency. Additionally, it outlines recommendations for assessing and controlling mutagenic impurities that reside or are reasonably expected to reside in the final drug substance or product.

FDA says the guidance also complements ICH “Q3A Impurities in New Drug Substances,” “Q3B(R2) Impurities in New Drug Products,” and “M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorizations for Pharmaceuticals.”

Additionally, the associated guidance documents were released:

• “M7(R2) Addendum: Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes”
• “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and Answers”