ICH M7: From Guideline to Practical Workflow 

This blog explores how protocol-driven (Q)SAR assessments became routine in ICH M7-based impurity evaluations. 

How ICH M7 Is Applied: Practical Steps for (Q)SAR Mutagenicity Assessment 

It has been 9 years since the publication of the Principles and Procedures for implementation of ICH M7 recommended (Q)SAR analyses¹, a paper Leadscope (Instem) helped initiate and promote. This publication has played an important role in shaping how drug impurities are assessed using in silico approaches. The publication, developed through cross-industry collaboration, provided practical guidance on implementing (Q)SAR predictions, incorporating expert review, and documenting assessments in alignment with the ICH M7 guideline². 

This initial publication paved the way for another pivotal paper³, focused on supporting indeterminate or out-of-domain results, which are two challenges frequently encountered in regulatory assessments. Together, these papers laid the foundation for a standardized approach that has been widely adopted across industry and regulatory workflows. Notably, both papers are open access and have been cited extensively, including in the ICH M7 Q&A document⁴, which highlights their continued relevance and utility. 

Tools Supporting ICH M7 Class Assessments 

The impact of these publications has extended beyond written publications. The principles and workflows have been implemented in software tools⁵ that support both internal industry assessments and regulatory submissions. For example, Leadscope’s ICH M7 protocol implementation integrates multiple prediction systems (statistical QSAR models, expert alerts) and database sources into a unified, documented decision framework to derive the M7 class assignment, Figure 1⁶. This implementation streamlines the assessment process while supporting expert review with traceability.  

Figure 1: ICH M7 interactive decision scheme summarizing QSAR results and expert review framework

Documented Procedures for Other Endpoints 

Importantly, the ICH M7 protocol implementation builds on the broader framework for in silico toxicology protocols developed and published in recent years. This includes similar structured workflows for endpoints such as genetic toxicology⁷ and skin sensitization⁸, and endocrine activity⁹. Each protocol follows a consistent architecture that enables transparency, repeatability, and integration of both model outputs and expert input. 

ICH M7 continues to influence other regulatory sectors as well, with similar approaches being applied to the assessment of genotoxic or mutagenic impurities in animal health products¹⁰ , E&Ls, and pesticide residues¹¹. Additionally, the foundation laid by the original principles and procedures publications^1,3 has enabled these applications by demonstrating how protocol-driven approaches can be both scientifically rigorous and practical. The development of protocol-driven tools has played a critical role in ensuring that assessments are not only scientifically robust but also consistent, efficient, and defensible, which are important in a regulatory environment. 

Key Takeways:

• The ICH M7² guideline has driven the adoption of standardized methodologies supporting (Q)SAR assessments.
• Standardized methodologies^1,3 have been incorporated into (Q)SAR protocols to support impurity assessments (ICH M7) and additional use cases in a scientifically rigorous manner. 
• Leadscope’s ICH M7 solution adheres to the established principles and procedures outlined in ICH M7 for impurity analysis.

You can access the seminal publications and the standardized methodologies for implementing (Q)SAR assessments within ICH M7 framework here:

Principles and procedures for implementation of ICH M7 recommended (Q)SAR analyses.

Principles and procedures for handling out-of-domain and indeterminate results as part of ICH M7 recommended (Q)SAR analyses.