An important application of computational methods at regulatory level is the evaluation of mutagenesis and carcinogenesis in impurities of pharmaceutical products. According to the International Conference on Harmonization (ICH), and in particular to the guide “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk” (ICH-M7) the computational toxicological evaluation must be carried out using complementary methodologies that predict the result of a bacterial mutagenicity test. Specifically, a methodology must consist on “rule-based expert systems” and the second methodology must be statistical in nature (QSAR). The models obtained by these prediction methodologies must follow the general validation principles established by the Organization for Economic Cooperation and Development (OECD).

The absence of structural alerts from these two complementary methodologies is sufficient to conclude that an impurity does not implies any mutagenic concern, and therefore no additional proof is needed.

In ProtoQSAR we have experience with the application of the different required methods (rule-based expert systems and statistical (Q)SARmodels), and the computational resultsare reviewed by our expert professionals in order to support the relevance and validity of the conclusions, and to provide a justification supporting the final conclusions.