French.pdf

Sartan-containing medicinal products are used to treat serious conditions like hypertension and heart or kidney diseases. However, they were found to be contaminated with N-nitrosamines, specifically NDMA and NDEA, which are potent mutagenic carcinogens. The contamination is thought to have occurred during the manufacturing process.

The European Medicines Agency assessed the risk of cancer associated with NDMA and NDEA exposure and estimated a theoretical excess cancer risk of 1:3390 (0.029%) based on animal studies. This risk is considered very low compared to the lifetime cancer risk in the European population of approximately 50%.

Measures have been taken to mitigate the risk, including recalls of affected batches, obligatory risk assessments for manufacturing processes, and modification of manufacturing processes to minimize contamination. A limit of 0.03 ppm for NDMA and NDEA in sartan APIs has been set, which will be enforceable after a 2-year transitional period.

In the meantime, interim limits have been set based on daily intakes according to ICH M7(R1) using toxicology data, which vary between different sartans. If NDMA and NDEA are detected in parallel in an API batch, the batch should be rejected. The principles used in this procedure should be applied by analogy to other nitrosamines, and any identification of other nitrosamines should be reported to competent authorities along with a toxicology assessment and corrective action plan.