Author/Editor		Amberg, Alexander; Beilke, Lisa; Bercu, Joel; Plaper, Andreja
Title		Principles and procedures for implementation of ICH M7 recommended (Q)SAR analyses
Type		članek
Vol. and No.		, št. Vol. 677
Publication year		2016
Volume		str. 13-24
ISSN		0273-2300 - Regulatory toxicology and pharmacology : RTP
Language		eng
Abstract		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.
Keywords		impurities ICH M7 mutagenic impurities Ames test toxicity databases expert review