Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part VII)
- 22 ноября 2018
- active substance, API, cancer, candesartan, carcinogen, CEP, drug product, EDQM, EMA, FDA, GC-MS/MS, GMP, human, hypertension, impurity, inspection, intermediate, irbesartan, losartan, MAH, manufacturer, manufacturing, manufacturing site, marketing authorisation holders, medicinal product, medicines, method, Mylan Laboratories Limited, N-nitrosodiethylamine, N-nitrosodimethylamine, NDEA, NDMA, nitrosamine, non-compliance, olmesartan, recall, review, sartans, specific ring structure, statement, suspension, test, tetrazole, valsartan, Zhejiang Huahai Pharmaceuticals,
Authorities in the EU are taking action after an impurity, N-nitrosodiethylamine (NDEA), was found in some batches of valsartan made by Mylan Laboratories Limited in Hyderabad, India.
EDQM has now suspended the manufacturer’s CEP (a certificate of compliance with European standards for quality testing), effectively prohibiting the use of its valsartan in EU medicines.
In addition, national authorities in the EU have started recalling affected batches of medicines containing Mylan’s valsartan and are conducting further tests to determine the extent of the contamination.
Following new information recently received by EDQM about the detection of low levels of N-nitrosodiethylamine (NDEA) in Valsartan manufactured by Mylan Laboratories Ltd, the EDQM has immediately suspended, as already mentioned above, the certificate of suitability (CEP)
– R1-CEP 2009-396-Rev 03/Valsartan
held by this company (to check the current status of CEP, please click here), until appropriate corrective actions are taken.
This is part of the on-going review of the manufacturing information submitted in all CEP applications for valsartan and other structurally related active substances.
It is important to note that Zhejiang Huahai Pharmaceutical – the first Chinese company with suspended CEP for valsartan (July 2018) – also manufactures intermediates for valsartan which are supplied to other manufacturers. As a result of the GMP non-compliance, Zhejiang Huahai intermediates can no longer be used for the manufacture of valsartan, and as a consequence 4 (four) CEPs for valsartan have been revised by the EDQM in order to remove reference to this manufacturing site.
FDA is posting a gas chromatography-tandem mass spectrometry GC-MS/MS method utilizing liquid injection for detecting the presence of impurities N - Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in valsartan drug products.
FDA has also posted questions and answers to assist health care professionals and patients.
We have already informed on our website about the ongoing review of valsartan and other ‘sartan’ medicines due to the detection of impurity N-nitrosodimethylamine (NDMA) as well as suspensions of CEPs by EDQM in Part I, Part II, Part III, Part IV, Part V and Part VI entries.
Sources: EMA, EDQM, FDA