Implementation Challenges for ICH’s New M7 Guideline on Mutagenic Impurities Will Present Themselves at Both the Development and Post-Approval Levels

Among the challenges that will present themselves to pharma companies in implementing ICH’s new M7 guideline on mutagenic impurities is the use of quantitative structure-activity relationship [QSAR] predictions in assessing the risks during development and for post-marketing changes.

The expectation in the guideline is that two orthogonal QSAR systems plus the standard Ames test be applied where mutagenicity may be at issue both for products in development and those undergoing higher-risk-to-patient changes.  QSAR represents a sophisticated set of physicochemical and statistical tools that some companies may have little or no experience with and will need to bring in-house and validate.

Mutagenicity risks should be evaluated, the guideline instructs, for post-approval changes involving new synthetic routes, new product degradants, or different dosage levels.

M7 was finalized at the ICH meeting in Minneapolis, Minnesota in June, and the Step 4 guideline was released in July.  EMA formally adopted the guideline in late September.   FDA and Japan’s Ministry of Health, Labor, and Welfare (MHLW) are expected to follow suit soon.

The primary final content of ICH’s elemental impurities guideline Q3D was also reached at the June meeting.  The Step 4 version is expected to be released shortly (IPQ October 23, 2014).

[CLICK HERE for the complete story.  Featured is a review of ICH M7 and the implementation challenges by FDA Expert Working Group (EWG) member Steve Miller.  Nonsubscribers can get information on IPQ subscription/licensing and individual story purchasing by contacting Karen Bertani (]