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

作者：Alexander Amberg, Lisa D. Beilke, Joel P. Bercu, Dave Bower, Alessandro Brigo, Kevin P. Cross, Laura L. Custer, Krista L. Dobo, E.J. Dowdy, Kevin A. Ford, Susanne Glowienke, Jacky Van Gompel, James Stephen Harvey, Catrin Hasselgren, Masamitsu Honma, Robert A. Jolly, Raymond A. Kemper, Michelle O. Kenyon, Naomi L. Kruhlak, Penny Sue Leavitt, Scott A. Miller, Wolfgang Muster, John J. Nicolette, Andreja Plaper, Mark W. Powley, Donald P. Quigley, M. Vijayaraj Reddy, Hans-Peter Spirkl, Lidiya Stavitskaya, Andrew J. Teasdale, Sandy K. Weiner, Dennie S. Welch, Angela T. White, Joerg Wichard, Glenn J. Myatt · 发表于：Regulatory Toxicology and Pharmacology · 年份：2016 · DOI：10.1016/j.yrtph.2016.02.004 · 被引用次数：113 · 研究领域：Carcinogens and Genotoxicity Assessment、Pesticide Exposure and Toxicity、Radiation Effects and Dosimetry

The ICH M7 guideline describes a consistent approach to identify, categorize, and control DNA reactive, mutagenic, impurities in pharmaceutical products to limit the potential carcinogenic risk related to such impurities. This paper outlines a series of principles and procedures to consider when generating (Q)SAR assessments aligned with the ICH M7 guideline to be included in a regulatory submission. In the absence of adequate experimental data, the results from two complementary (Q)SAR methodologies may be combined to support an initial hazard classification. This may be followed by an assessment of additional information that serves as the basis for an expert review to support or refute the predictions. This paper elucidates scenarios where additional expert knowledge may be beneficial, what such an expert review may contain, and how the results and accompanying considerations may be documented. Furthermore, the use of these principles and procedures to yield a consistent and robust (Q)SAR-based argument to support impurity qualification for regulatory purposes is described in this manuscript.