Notice: Implementation of International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) Guidance Document: M7(R1)

January 19, 2018
Our file number: 18-100716-962

Health Canada is pleased to announce the implementation of the ICH M7(R1) guidance: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.

This guidance has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. The ICH Assembly has endorsed the final draft and recommended implementation by membership of ICH.

By way of this notice, Health Canada is informing stakeholders that, further to section 9.2 of the ICH M7(R1) guidance, for actual and potential synthetic impurities (per section 5.1 of ICH M7(R1)) and/or degradation products (per section 5.2 of ICH M7(R1)) that have been classified as a Class 1 (and for which a monograph is not described in the Addendum), Class 2, Class 3, Class 4 or Class 5 impurity (per Table 1 of section 6 of ICH M7(R1)), if any of the following sources of data are used to support the assigned classification, the documentation (as applicable to each impurity or degradation product evaluated) should be submitted with the marketing application at the time of filing:

• A copy of the literature reference(s) supporting the assigned classification,
  
• Final and complete bacterial mutagenicity assay study reports,
  
• Final and complete in silico (Q)SAR study reports. It is also recommended that the Simplified Molecular Input Line Entry System (SMILES) string for each assessed impurity, QSAR Model Reporting Format, and QSAR Prediction Reporting Format be submitted. The QSAR Model/Prediction Reporting Format (QM/PRF) was developed by the Joint Research Centre (JRC) and EU Member State authorities as a harmonised template for summarising and reporting key information on QSAR models, including the results of any validation studies as well as for providing supplementary information on applicability of the model to a given chemical.

These documents (formatted as .pdf) should be placed under the Module 4.2.3.7.6 Impurities heading using node extensions or Study Tagging Files (STFs) based on each impurity. For more information on how to provide Regulatory Activities in eCTD format refer to the Guidance Document: Preparation of Drug Regulatory Activities in the Electronic Common Technical Document Format (section 2.3.4 ‘Modules 2 to 5 Folders’ and section 3.1 ‘File Formats’).

In implementing this ICH guidance, Health Canada endorses the principles and practices described therein. This document should be read in conjunction with this accompanying notice and with the relevant sections of other applicable Health Canada guidances. This and other Guidance documents are available on the ICH Website {hyperlink}. Please note that the ICH website is only available in English. If you would like to request a copy of the French version of the document, please contact the HPFB ICH inbox.

It is recognized that the scope and subject matter of current Health Canada guidances may not be entirely consistent with those of the ICH guidances that are being introduced as part of our commitment to international harmonization and the ICH Process. In such circumstances, Health Canada adopted ICH guidances take precedence.

Health Canada is committed to eliminating such discrepancies through the implementation of a phased-in work plan that will examine the impact associated with the adoption of ICH guidances. This will result in the amendment or, depending on the extent of revisions required, withdrawal of some Health Canada guidances.

Should you have any questions or comments regarding the content of the guidance, please contact:

Health Canada - ICH Coordinator
E-mail: HPFB_ICH_DGPSA@hc-sc.gc.ca