In November 2020, the CHMP adopted an Opinion concluding that the outcome of the Article 31 referral on angiotensin-II-receptor antagonists (sartans) containing a tetrazole group (EMEA/H/A-31/1471) should be aligned with the outcome of the Article 5(3) assessment on nitrosamines (EMEA/H/A-5(3)/1490).
The main change concerns the limits for N-nitrosamines, which previously applied to the active ingredients and will now apply instead to the finished products.
OUR CAPABILITIES
Thanks to the long-standing experience in nitrosamines analyses, Mérieux NutriSciences’ Pharmaceutical and R&D Divisions have developed and validated suitable high sensitive LC-MS/MS methods for NDEA and NDMA determination in sartans-based drug products with LoQ lower than 5ppb, suitable for waiving / skip tests according to EMA Guideline. In order to quickly respond to our customers, a dedicated line for sartans-based drug products was implemented to offer on-demand rush services and ensuring deadline compliance.
THE NEW DEADLINES
30 June 2021
Limits for N-nitrosodimethylamine (NDMA) (96 ng/day) and N nitrosodiethylamine (NDEA) (26.5 ng/day) should be implemented for finished products.
26 September 2022
The MAH must ensure that the manufacturing processes of finished products is reviewed for the potential risk of formation of N-nitrosamines and changed if necessary to minimise nitrosamine contamination as much as possible.
Please refer to the Questions & Answers on implementation document for complete information.