Assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products - Scientific guideline

The purpose of this guideline is to provide a practical framework that is applicable to the identification, categorisation, qualification, and control of these mutagenic impurities, to limit potential carcinogenic risk associated with the exposure to potentially mutagenic impurities. This guideline is intended to complement VICH GL10 and VICH GL11. This guideline considers both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that remain or are reasonably expected to remain in the final drug substance or VMP.

Keywords: Impurity, mutagenic, carcinogenic, DNA - reactive

Current effective version

Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products

AdoptedLegal effective date: 01/07/2020Reference Number: EMA/CVMP/SWP/377245/2016Summary:

The synthesis of drug substances involves the use of reactive chemicals, reagents, solvents, catalysts, and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities reside in all drug substances and associated veterinary medicinal products (VMPs). While VICH GL10: Impurities in New Veterinary Drug Substances (Ref. 1) and VICH GL11 (Ref. 2): Impurities in New Veterinary Medicinal Products provide guidance for qualification and control for the majority of the impurities, limited guidance is provided for those impurities that are DNA reactive. The purpose of this guideline is to provide a practical framework that is applicable to the identification, categorisation, qualification, and control of these mutagenic impurities, to limit potential carcinogenic risk associated with the exposure to potentially mutagenic impurities. This guideline is intended to complement VICH GL10 and VICH GL11.

Document history

Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products

AdoptedLegal effective date: 01/07/2020Reference Number: EMA/CVMP/SWP/377245/2016Summary:

The synthesis of drug substances involves the use of reactive chemicals, reagents, solvents, catalysts, and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities reside in all drug substances and associated veterinary medicinal products (VMPs). While VICH GL10: Impurities in New Veterinary Drug Substances (Ref. 1) and VICH GL11 (Ref. 2): Impurities in New Veterinary Medicinal Products provide guidance for qualification and control for the majority of the impurities, limited guidance is provided for those impurities that are DNA reactive. The purpose of this guideline is to provide a practical framework that is applicable to the identification, categorisation, qualification, and control of these mutagenic impurities, to limit potential carcinogenic risk associated with the exposure to potentially mutagenic impurities. This guideline is intended to complement VICH GL10 and VICH GL11.

Overview of comments received on guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products (EMA/CVMP/SWP/377245/2016)

Reference Number: EMA/CVMP/SWP/610519/2017

Draft guideline on assessment and control of DNA reactive, mutagenic impurities in veterinary medicines

Consultation dates: 24/02/2017 to 31/08/2017Draft: consultation closedReference Number: EMA/CVMP/SWP/377245/2016Summary:

This guideline focuses on deoxyribonucleic acid (DNA) reactive substances that can potentially cause DNA damage when present at low levels leading to mutations and therefore, potentially causing cancer. Its purpose is to provide a practical framework for identifying, categorising, qualifying and controlling these mutagenic impurities to limit any potential carcinogenic risk. It considers both safety and quality risk management measures to establish levels of impurities with a negligible carcinogenic risk.

Concept paper for a guideline on limits for genotoxic impurities

Consultation dates: 18/01/2013 to 30/04/2013Draft: consultation closedReference Number: EMA/CVMP/SWP/398880/2012Summary:

In the absence of guidance on limits for genotoxic impurities in veterinary medicinal products, the Committee for Medicinal Products for Veterinary Use (CVMP) recommends the development of a guideline to describe a practical approach on how to deal with genotoxic impurities, taking account of both target animals and consumer safety.