News on Nitrosamine Impurities

Risk evaluation needed for all APIs until 26.03.2020!

Have you finalized your risk assessment for all your APIs and sent to the Authorities in time? Do you know what's coming next and where to find the relevant information? 

If you have a risk identified and sent the corresponding information to the Authorities, you will now move to step 2 (testing phase) and have to report that either no nitrosamines are present or that you have detected nitrosamines. This step 2 defines further activities, such as review of your manufacturing process, adaption of specifications, methods, batch data etc and finally submission of the corresponding variations. Activities on step 3 should be completed by September 2022.


In Valsartan a potential carcinogenic contaminant was found in 2018: N-Nitrosodimethylamine (NDMA) and later also N-nitrosodiethylamine (NDEA). This was due to a change of synthesis at the API-manufacturing site of Zhejiang Huahai Pharmaceutical Co. in 2012. NDMA: may arise in an acid-catalyzed reaction of dimethylamine with nitrite salts. The consequences were recalls of various products (since 04.07.2018). Additional potentially genotoxic impurities were found in Sartans. 

As there is a potential risk of contamination of drug products other than those containing sartans, a risk evaluation was requested for all other products (i.e. Non-sartan APIs). Therefore EMA advised companies on steps to take to avoid nitrosamines in human medicines in Sept. 2019, proposing the step-wise approach. This started with risk evaluation for all APIs (step 1 to be completed by 26.03.2020), leading to confirmatory testing (step 2) up to submission of variations (step3).

You can find more information about nitrosamine impurities and the risk assessment here:

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