The first version of the Sharing Drug Substance M7 information to HA and MAH: “How to do” document -Interpretation of the ICH M7 guideline and other relevant guidelines with regard to M7 data sharing and the associated templates were finalised in March and April 2023 and are now available on the APIC website. They can be seen as complementary and explanatory to the ICH Guideline Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuitcals to limit potential carcinogenic risk M7(R2), which is now available in revision 2.
ICH M7 guideline, which describes recommendation on how to perform assessment of mutagenic potential of impurities residing in drug substances, was first published in year 2013, and is required to be implemented since January 2016. The guideline briefly states what data regarding performed mutagenic impurities (MIs) assessment the drug substance (DS) manufacturer should include in regulatory documentation. Based on the latter, it is important for DS manufacturers to assess the mutagenic potential of impurities, and share relevant data regarding the assessment with health authorities (HAs) and marketing authorization holders (MAHs) to review and assure safety of the drug product (DP). However, it seems that different DS manufacturers have different approaches to data sharing to both HAs and MAHs. The assessment of impurities to assure safety is crucial throughout the development process and life-cycle management of a DS/ drug product (DP). The question on what data DS manufacturers should share, especially with MAH, gained additional importance with the Valsartan issue and newly published Nitrosamine guidelines, which require detailed data to be shared with MAH. Furthermore, in the EU, MAH is responsible for DS quality as per the legislation. Therefore, the Industry should discuss and define what data regarding MIs assessment should be shared with HAs and MAHs.
The responsible task force of APIC, which is a sector group of the European Chemical Industry Council (CEFIC), wants to use the “How to do” document to provide recommendations and explanations for active substance manufacturers to facilitate data exchange with regulatory authorities and marketing authorisation holders with regard to mutagenic impurities and their consideration. Here, the recommendations for new submissions and notifications of changes as well as for fermentatively and semi-synthetically produced active substances are described and considered separately.
The objective of the document is to present APIC recommendations on what data regarding MIs assessment of the DS should be shared with HAs and MAHs. The document describes the APIC M7 Taskforce current thinking on the topic and should be viewed as recommendations, unless specific regulatory requirements are cited. In addition, the “Appendix – Decision tree on Retrospective M7 Assessment (prepared in Step 1 of APIC M7 TF)” lists some possible scenarios and decision paths for the M7 assessment.