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USFDA Guidance: ICH M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities

Earlier today (25 June, 2023) the United States Food & Drug Administration's Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research released final guidance on "M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk".


A mutagenic impurity is defined as an impurity that has been demonstrated to be mutagenic in an appropriate mutagenicity test model (e.g., bacterial mutagenicity assay).

The guidance emphasizes the need to consider both safety as well as quality risk management in establishing levels of mutagenic impurities that are expected not to pose a significant carcinogenic threat.


The guidance outlines recommendations for the assessment and control of mutagenic impurities that reside or are reasonably expected to reside within the final drug substance or product depending on human usage conditions.


The purpose of this guidance is to provide guidance for the development of new drug substances and new drug products in the clinical stage and in the application for marketing.


Additionally, it applies to products with a drug substance that is present in a previously approved product, and to new marketing applications for products with a drug substance that is present in a previously approved product, provided that:

  • Changes to the drug substance synthesis result in new impurities or increased acceptance criteria for existing impurities

  • Changes in the formulation, composition, or manufacturing process result in new degradation products or increased acceptance criteria for existing degradation products

  • Changes in indication or dosing regimen are made, which significantly affect the acceptable cancer risk level

Click this LINK to know more about this guidance and click this LINK to know the Questions and Answers related to this guidance. Check out the supplemental updated M7(R2) Addendum related to this guidance by clicking this LINK.

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