Following new information received recently by EDQM about the presence of nitrosamine impurities in drug substances covered by certificates of suitability (CEPs), the EDQM has taken immediate actions on CEPs until appropriate corrective actions will have been implemented by the relevant company:
- due to the detection of low levels of N-nitrosodiethylamine (NDEA), suspension of the CEP R1-CEP 2010-033-Rev 01/Irbesartan and R1-CEP 2010-139-Rev 00/losartan potassium, process II, which are both held by ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.
This is part of the on-going review of the CEP applications and exchange of information with international partners for valsartan and other ARBs (Angiotensin II receptor blockers).
NDEA is classified as probable human carcinogen (substance that may cause cancer).
Nitrosamine impurities can be formed due to the synthetic process used to manufacture valsartan and other ARB medicines or they may be introduced into the active substance when recovered materials which are contaminated with these impurities are used in a manufacturing process. Holders of CEPs are therefore requested to immediately inform EDQM of any contamination found in valsartan and or other ARBs manufactured and supplied using a CEP.