• M7 Mutagenic impurities

    Code Document Title Previously coded
    • Description :

      The ICH M7 Guideline was finalised 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 finalised in 2017 to summarise 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.

      The M7(R2) EWG is currently undertaking a maintenance of the Guideline, which will result in the future ICH M7(R2) version.

      Implementation :

      Step 5


      EC, EuropeTo be notified

      FDA, United States Published in the Federal Register 1 March 2018, Vol. 83, No. 50, p. 11210 - 12

      Health Canada, Canada Implemented 15 January 2016, File #: 15-114011-514

      MHLW/PMDA, Japan Adopted 27 June 2018, PSEHB/PELD 0627-1

      Swissmedic, Switzerland To be notified