by Isabel Pascual

The European regulators (European Medicines regulatory network) has released recommendations on impurities in medicines, as a result of the case of Nitrosamine impurities found during 2018 in Sartan Medicines in Europe. 

Remember that during 2018 there was a massive recall of various products (valsartan, candesartan, irbesartan, losartan and olmesartan), and a subsequent banning of usage of specific APIs from certain manufacturers.   The case triggered the immediate revision of the monographs for these molecules, including new limits for impurities. The recommendations of the lessons learnt exercise will complement the outcome of an already initiated procedure (Art 5(3)) which will provide the key scientific opinion on the presence of nitrosamine impurities in human medicines containing chemically synthesized active substances

The full exercise focused on Nitrosamines in Sartans, but the authorities and regulations have extended the learnings and scientific opinion, creating guidances on the aim to help reduce the risk of impurities being present in other medicines and procedures to ensure better and faster management of cases of unexpected impurities in the future.  As a result of this initiative, in September 2019, EMA launched an additional procedure to provide guidance to companies that make and market medicines in the EU.

Now these guidance has been issued as a set of recommendations which focus on the clarification of roles & responsibilities of the different players of the supply chain of pharmaceutical products -- manufacturers, importers and distributors.  It also points out to guidance changes on reporting, communication and cooperation on the subject of impurities within the framework of GMPs. 

The European Commission has proposed also the revision of the general monograph for substances for pharmaceutical usage, to include clear requirements for manufacturers to address the risk of contamination of substances -- initially, by Nitrosamines impurities, but is expected that also for others.  The proposal has been published for public inquiry, prior to become legally binding. 


You can find all the information at the EDQM webpage and the HMA page.