CMDh raising risk awareness on Nitrosamines Impurities

Taking into account their knowledge of the manufacturing processes and the potential sources of nitrosamine impurities, the manufacturers of API and finished products should cooperate with MAHs to prevent nitrosamine formation and contamination of human medicinal products.

• Step 1 risk evaluation: MAHs should perform risk evaluation of their medicinal products containing chemically synthesised API using quality risk management principles, as per ICH Q9 guideline and principles described in ICH M7 guideline related to toxicology assessment and control strategy. Prioritization of products is prescribed and risk evaluation of high risk / high priority products should be done immediately (e.g. higher daily exposure and chronic use). Risk evaluation documents should be made available upon request.
• Step 2 confirmatory testing: if a risk of presence of nitrosamines is identified, then confirmatory testing are required by the use validated and sensitive methods. MAHs should inform the competent authorities immediately if tests confirm the presence of an nitrosamine impurity irrespective of the amount detected.
• Step 3 changes to the marketing authorisation: MAHs should apply for a variation in a timely manner to introduce any required changes, such as amendment of the manufacturing process or changes to product specifications.

Confirmatory testing and submission of Variations to the Marketing Authorization should be concluded at the latest within 3 years of the publication of the CMDh notification, i.e. by September 2022.