M7 Mutagenic Impurities
M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk
The ICH M7 Guideline was finalized in 2014 offering guidance on analysis of Structure Activity Relationships (SAR) for genotoxicity. Furthermore, it is intended to resolve questions such as whether impurities with similar alerts that potentially have similar mechanism of action should not be combined in calculating a Threshold of Toxicological Concern (TTC) and whether the TTC may differ based on differences in the approved duration of use.
To complement this ICH M7 Guideline an Addendum was finalized in 2017 to summarize known mutagenic impurities commonly found or used in drug synthesis. The intent of this Addendum is to provide useful information regarding the acceptable limits of known mutagenic impurities/carcinogenic and supporting monographs
Maintenance Process
A maintenance process has been done to incorporate acceptable limits (Acceptable Intakes (AIs) or Permitted Daily Exposures (PDEs)) for new DNA reactive (mutagenic) impurities and revising acceptable limits for impurities already listed in the Addendum as new data becomes available. Data and/or proposals pertaining to the revision of the ICH M7(R1) Guideline with supporting information can be submitted directly to the ICH Secretariat from either an ICH Member or Observer or other interested ICH stakeholders.
Date of Step 4: 1 June 2017
Status: Step 5
Guidelines (Click the links below for complete guidelines)
Endorsed Documents (Click the links below for complete guidelines)
WG Presentations / Trainings (Click the links below for complete guidelines)
M7(R2) Maintenance EWG/IWG Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk
The M7(R2) Maintenance EWG/IWG is currently undertaking a maintenance of the M7(R1) Guideline to incorporate acceptable limits (Acceptable Intakes (AIs) or Permitted Daily Exposures (PDEs)) for new DNA reactive (mutagenic) impurities and revising acceptable limits for impurities already listed in the Addendum as new data becomes available, which will result in the future ICH M7(R2) version.
In November 2018, the Assembly endorsed the new area of work of the M7(R2) Maintenance EWG/IWG as outlined in the revised Concept Paper which was approved by the ICH Management Committee. As a result, Q&As will be developed to clarify and address Quality and Safety issues and concerns that have been identified from experience through implementation of M7 since its publication in 2014.
Date of Step 2b: 6 October 2021
Status: Step 3
Guideline (Click the links below for complete guidelines)
Endorsed Documents (Click the links below for complete guidelines)
Q&As
The M7(R2) Maintenance EWG/IWG is developing Q&As to clarify and address Quality and Safety issues and concerns that have been identified from experience through implementation of M7 since its publication in 2014.
Date of Step 2b: 29 June 2020
Status: Step 3
WG Presentation/Trainings (Click the links below for complete guidelines)
*These Guidelines Belongs to ICH website.
