Specific research priorities for FY 2025 were identified within each of the eight research areas enumerated below. The numbering of the eight research areas does not reflect any relative prioritization among the research areas.
1. 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 2025 science and research priorities specifically include:
- Evaluating practical strategies that may mitigate the potential risks of harmful impurities such as nitrosamines, and investigating the effect of these strategies on the absorption and/or the bioavailability of active pharmaceutical ingredients (APIs), including utilizing modeling and simulation approaches to assess the risk of altering the performance of a generic product in the event of a reformulation, and to explore a path 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 quantitation 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, and the influence of manufacturing processes 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
The remaining numbers 2 to 8 are as follows:
2. Enhance the Efficiency of Equivalence Approaches for Complex Active Ingredients
3. Enhance the Efficiency of BE Approaches for Complex Dosage Forms and Formulations
4. Enhance the Efficiency of BE Approaches for Complex Routes of Delivery
5. Enhance the Efficiency of Equivalence Approaches for Complex Drug-Device Combination Products
6. Improve the Efficiency of BE Approaches for Oral and Parenteral Generic Products
7. Facilitate the Utility of Model-Integrated Evidence (MIE) to Support Demonstrations of BE
8. Expand the Use of Artificial Intelligence (AI) and Machine Learning (ML) Tools
https://www.fda.gov/drugs/generic-drugs/fy-2025-gdufa-science-and-research-priorities