Nitrosamines remain a Science priority for the FDA. Specific research priorities for FY 2026 were identified within each of the eight research areas enumerated below. The numbering of the eight research areas does not indicate any relative prioritization among them.
Develop Methods for Generics to Address Impurities such as Nitrosamines:
This research area focuses on understanding how ingredients in drug products may either contribute to or mitigate the formation of potentially harmful impurities such as nitrosamine adducts (e.g., nitrosamine drug substance-related impurities (NDSRIs)), evaluating the risk of human exposure to these impurities, and developing methods for abbreviated new drug application (ANDA) applicants to efficiently address the potential risks. FY 2026 science and research priorities specifically include:
- Exploring approaches, including modeling and simulation, for the efficient and economically feasible reformulation of biopharmaceutics classification system (BCS) Class IV drugs to reduce nitrosamine impurities.
- Developing analytical methods and approaches using orthogonal methods for the identification and quantification of nitrosamines and precursors in ingredients, including considerations for the distribution of nitrosamines and their corresponding precursors in an ingredient or drug product.
- Understanding the mechanisms of nitrosamine formation in APIs and drug products, such as the reactivity of different functional groups in APIs (e.g., tertiary amines beyond secondary amines), the role of impurities in excipients, or other factors that may help to predict the formation of nitrosamines and the risks of their formation under relevant conditions for pharmaceuticals.
- Developing acceptable intake limits for impurities such as nitrosamines, including NDSRIs, using risk assessment paradigms that consider mutagenicity evaluations (in vitro or in vivo), metabolism, in silico evaluations (such as quantitative structure activity relationship modeling), and carcinogenic potency assessments.