Identifying the Risk of Formation of Nitrosamines and Other Potentially Mutagenic Impurities during API Manufacture Using <i>In Silico</i> Risk Assessment

Synthetic routes to drug products typically introduce several potentially mutagenic impurities (PMIs) which require controlling a safe level in the final substance, generally directed by control options within ICH M7 guideline. These are most commonly introduced due their specific synthetic utility; however, formation of PMI can also occur indirectly from combination otherwise nonmutagenic sources, as was case for NDMA valsartan. Identifying these risks currently relies on manually assessing route, process requiring extensive knowledge and liable oversight. Herein we report development functionality an silico risk assessment tool facilitate identification stages PMIs industrial and/or regulatory users.