Final Guidance for Industry M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk
This guidance aims to provide a framework for the identification, categorization, qualification, and control of mutagenic impurities. While ICH Q3A Impurities in New Drug Substances (Revision 2) (Q3A) and Q3B(R2) Impurities in New Drug Products (Q3B) provide guidance for qualification and control for the majority of the impurities, the guidance acknowledges that there was limited guidance available for those impurities that are DNA reactive. The guidance is applicable to new drug substances and new drug products during their clinical development and subsequent applications for marketing. It also applies to post-approval submissions of marketed products, and to new marketing applications for products with a drug substance that is present in a previously approved product if any of the following criteria apply:
- 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.
Assessment of the mutagenic potential of impurities as described in this guidance is not intended for the following types of drug substances and drug products: Drug substances and drug products derived from the following sources are out of scope of the guidance document: biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation, herbal, and crude products of animal or plant origin.