One of the most widely used applications of (Q)SAR is to support the assessment of pharmaceutical impurities aligned with the ICH M7 guideline1. Such assessments include the use of two complementary (Q)SAR methodologies alongside an expert review to assign the impurities to a specific class (classes 1 to 5 are outlined in the guideline). To support such implementation, Instem (through the Leadscope solution) developed bacterial mutagenicity and carcinogenicity databases, (Q)SAR models, and workflow tools2. We also developed a number of position papers, through cross-industry collaboration, to address issues related to the practical implementation of the ICH M7 guideline, including what should be addressed as part of an expert review and how to handle out-of-domain results.3,4,5,6
In 2020, a similar guideline was issued to support the assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products by the European Medicines Agency5. Although there are some differences to ICH M7, the guideline adopts similar recommendations on the use of (Q)SAR approaches.
If you would like to discuss this application of (Q)SAR methods, please get in touch via email@example.com.
- ICH, M7 (R1) Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk, 2017. https://database.ich.org/sites/default/files/M7_R1_Guideline.pdf.
- Myatt, G.J., et al., 2022. Implementation of in silico toxicology protocols within a visual and interactive hazard assessment platform. Comput. Toxicol. 21, 100201. https://doi.org/10.1016/j.comtox.2021.100201
- E. Ahlberg, et al., Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity, Regul. Toxicol. Pharmacol. 77 (2016) 1–12. https://doi.org/10.1016/j.yrtph.2016.02.003.
- Amberg, A., et al. (2018) Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: is aromatic N-oxide a structural alert for predicting DNA-reactive mutagenicity? Mutagenesis 34, 67–82. 10.1093/mutage/gey020
- Amberg, A., et al., 2016. Principles and procedures for implementation of ICH M7 recommended (Q)SAR analyses. Regul. Toxicol. Pharmacol. 77, 13–24. https://doi.org/10.1016/j.yrtph.2016.02.004
- A. Amberg, et al., Principles and procedures for handling out-of-domain and indeterminate results as part of ICH M7 recommended (Q)SAR analyses, Regul. Toxicol. Pharmacol. 102 (2019) 53–64. https://doi.org/10.1016/j.yrtph.2018.12.007.
- Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products, 2020. Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products (europa.eu)