Consumer Healthcare Products Association responded to the latest FDA’s nitrosamine guidance. Do you agree with their comments?
Page 23 – FDA recommends conclusion of NDSRI confirmatory testing of drug products and submission of required changes in drug applications by August 1, 2025. This timeline was established in 2023 and for our industry, it is unrealistic. Evolution of understanding nitrosamine formation in finished products has been slow and while progress is being made, much remains to be done. This includes standardization of assays for nitrosamine impurities, generation of additional data and possible submission of alternative acceptable limits to FDA for review and approval. Until very recently, our members have been unable to get necessary feedback from FDA on research programs and other steps towards further understanding NDSRI safety. A more realistic timeline for our industry is August 2027 to complete all necessary work for full implementation, including Enhanced Ames Tests (EATs) and generating other potential safety data, reformulation, manufacturing validation and stability testing.
Pages 11-13 – When considering acceptable intakes of nitrosamines, CHPA encourages FDA to continue to participate and consider insights from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the Health and Environmental Sciences Institute (HESI), including adopting Less-than-Lifetime (LTL) exposure limits for products with appropriate justification. We feel this is particularly appropriate for OTC medicines, many of which are used on an acute basis. It would also accord with policies currently in place elsewhere in the world. We appreciate FDA’s interactions with global regulatory authorities and ask that FDA consider approaches, such as in Europe, where a 30% threshold for reduced (e.g., skip) testing is acceptable for nitrosamines.