Following the Committee for Human Medicinal Products (CHMP) Opinion on the presence of N-nitrosamines in sartans, the European Medicines Agency (EMA) has released a Q&A guidance document to aid manufacturers in implementing the CHMP Opinion.
The guidance relates to five sartan medicines with a tetrazole ring (candesartan, irbesartan, losartan, olmesartan and valsartan) which have the potential to form harmful N-nitrosamines. Whilst appropriate control strategies and risk minimisation measures are already a requirement for manufacturers, several new and revised conditions have been introduced with the new guidance:
- The marketing authorisation holder (MAH) must ensure a review of manufacturing processes of active substance for the potential of N-nitrosamine formations. This risk must be minimised as much as possible in line with the latest recommendations adopted by the CHMP
- Application of the aforementioned principles of risk minimisation of nitrosamine impurities in active substances must also be separately applied to the finished product
- A new condition which specifies limits of 96ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/day for N-nitrosodiethylamine (NDEA) in the finished product. This limit (which should be included in the finished product specification) should be calculated by dividing the respective limit (ng) by the maximum daily dose (mg).
The document concludes with a Q&A for manufacturers to aid them with the practical implementation of these revised conditions.
The full document can be found here.