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 (Version 1 March 2023)


Impurities, originating from chemical synthesis and/or degradation, reside in all drug substances. In order to assure safety of the drug substance, levels of impurities in drug substances need to be qualified and controlled. Furthermore, some impurities have the potential to be DNA-reactive and therefore cause mutations with carcinogenic risk to the patients; these impurities are referred to as (potentially) mutagenic impurities. Based on the latter, it is important for drug substance (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). The assessment of impurities to assure safety is crucial throughout the development process and life-cycle management of a DS/ DP. 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 DS manufacturer should include in regulatory documentation. However, it seems that different DS manufacturers have different approaches to data sharing to both HAs and MAHs. 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 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.


Your can download APIC´s M7 How to do document here.