risk assessment - fda guidelines for ndma excellent document
This is a PDF document titled "Risk Assessment - FDA Guidelines for NDMA excellent document.pdf" created in June 2025. It contains a detailed presentation from the U.S. FDA's Center for Drug Evaluation and Research about the control and risk assessment of nitrosamine impurities in human drugs. The content covers FDA guidance, root causes, analytical methods, mitigation strategies, timelines, and regulatory expectations related to nitrosamines such as NDMA in pharmaceuticals to ensure drug safety and quality. The document is technical and regulatory in nature, intended for industry stakeholders and regulators.
Questions this document answers
They pose potential carcinogenic risk, which is why they are controlled in pharmaceuticals based on ICH M7 guidance.
NMBA is a nitrosamine impurity found in some sartans. It has an acceptable intake limit of 96 ng/day and is monitored due to its mutagenic risk in pharmaceuticals.
It covers root causes, acceptable intake limits, recommendations to manufacturers, a three-step mitigation strategy, reporting changes, and timelines for implementation.
It involves assessing the potential for reactive amines and nitroso compounds in manufacturing steps, reagents, intermediates, and suppliers to identify nitrosamine risk.
FDA recommends validated orthogonal tests with specificity and sensitivity to detect nitrosamines at trace levels, including methods posted for ARBs, ranitidine, metformin, rifampin, and rifapentine.