Regulatory Aspects in Assessment and Control of DNA Reactive (Mutagenic) Impurities in API’s and Final Products to Limit Potential Cancer Risk as Per ICH M7

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Mansi A. Chandramore
Swapnil S. Chitte
Pratibha U. Patil
Kishor S. Salunkhe
Dimple Marathe
Kiran R. Divekar
Gauri R. Borude


The ICH M7 guidelines for DNA reactive (mutagenic) impurities elaborate on the assessment and control of genetically damage-causing impurities in API and finished products. This suggested adopting the in-sillico (Q) SAR models and bacterial mutagenicity assays by industries and regulatory agencies for evaluation, as well as the acceptance of various control strategies to lower the risk of carcinogenic properties of substances. This paper discusses principles for evaluating and assessing such impurities that will support the path of regulatory submissions.

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Chandramore , M. A. ., Chitte , S. S. ., Patil, P. U. ., Salunkhe, K. S. ., Marathe, D. ., Divekar, K. R. ., & Borude, G. R. . (2023). Regulatory Aspects in Assessment and Control of DNA Reactive (Mutagenic) Impurities in API’s and Final Products to Limit Potential Cancer Risk as Per ICH M7. Journal of Coastal Life Medicine, 11(2), 187–192. Retrieved from


Borths CJ, Argentine MD, Donaubauer J, Elliott EL, Evans J, Kramer TT, Lee H, Parsons R, Roberts JC, Sluggett GW, Teasdale A. Control of mutagenic impurities: Survey of pharmaceutical company practices and a proposed framework for industry alignment. Organic Process Research & Development. 2021 Mar 3; 25(4):831-7.

Valerio Jr LG, Cross KP. Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities. Toxicology and applied pharmacology. 2012 May 1; 260(3):209-21.

Guideline ICH. Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk M7. International conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH): Geneva 2014.Establishing best practices in the application of expert review of mutagenicity under ICH M7.

Teasdale A. ICH M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. ICH Quality Guidelines: An Implementation Guide. 2017 Sep 27:667-99.

Barber C, Hanser T, Judson P, Williams R. Distinguishing between expert and statistical systems for application under ICH M7. Regulatory Toxicology and Pharmacology. 2017 Mar 1;84:124-30.

Snodin DJ. Mutagenic impurities in pharmaceuticals: A critical assessment of the cohort of concern with a focus on N-nitrosamines. Regulatory Toxicology and Pharmacology. 2023 Apr 26:105403.

Kropko ML, Jaen JC, Theiss JC, Wold S, Caprathe BW, Wise LD. Chemical purity and mutagenicity: case study of a drug in development. Mutation Research Letters. 1992 Apr 1;281(4):233-8.

Honma M. Thresholds of Toxicological Concern for Genotoxic Impurities in Pharmaceuticals. In Thresholds of genotoxic carcinogens 2016 Jan 1 (pp. 103-115). Academic press.

Liu KT, Chen CH. Determination of impurities in pharmaceuticals: why and how?. InQuality management and quality control-new trends and developments 2019 Jan 31 (pp. 1-17). London: IntechOpen.

Regulska K, Michalak M, Murias M, Stanisz B. Genotoxic impurities in pharmaceutical products–regulatory, toxicological and pharmaceutical considerations. Journal of Medical Science. 2021 Mar 30; 90(1):e502-.

Glowienke S. The new ICH M7 Guideline on the assessment and control of mutagenic impurities in pharmaceuticals–Implications on its practical use. PharmInd. 2016.

Giordani A, Kobel W, Gally HU. The overall impact of the regulatory requirements for genotoxic impurities on the drug development process. European Journal of pharmaceutical sciences. 2011 May 18; 43(1-2):1-5.

Raman NV, Prasad AV. Regulatory Expectations towards Genotoxic Impurities in Drug Substances: DMF and ASMF Perspective. Organic Process Research & Development. 2014 Jul 18; 18(7):834-5.

Jouyban A, Parsa H. Genotoxic impurities in pharmaceuticals. Toxicity and Drug Testing. 2012 Feb 10:387-417.

Nagao M, Sugimura T, Matsushima T. Environmental mutagens and carcinogens. Annual review of genetics. 1978 Dec; 12(1):117-59.