Europe – Update on the review of CEP applications for sartans

Following new information received recently 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 are implemented by the relevant companies:

  • due to the detection of low levels of N-nitrosodiisopropylamine (NDIPA), suspension of the CEP R0-CEP 2011-231-Rev 00/Valsartan held by Signa de C.V.
  • due to the detection of low levels of N-nitrosodiethylamine (NDEA), suspension of the CEP R1-CEP 2011-174-Rev 00/Valsartan, Process II held by Aurobindo Pharma Limited.

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).

NDIPA and NDEA are classified as probable human carcinogens (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.