The European Medicines Agency (EMA) has taken a significant step towards ensuring the safety of medications by updating its recommendations for testing N-nitrosamines, a class of chemicals linked to an increased cancer risk.
N-nitrosamines can form unintentionally during the manufacturing process of some medicines. While their presence is generally very low, even small amounts can be harmful. The updated guidance focuses on improving the detection of these impurities, particularly N-nitrosamine drug substance related impurities (NDSRIs), a recently identified class with a more complex structure.
Why the Change?
The standard Ames test, a common method used to assess a compound’s ability to cause mutations (mutagenicity), has limitations. Studies have shown it may not be sensitive enough to detect certain N-nitrosamines, especially NDSRIs.
Enhanced Ames Test (EAT) for More Reliable Detection
The EMA’s update outlines a more robust testing approach – the Enhanced Ames Test (EAT). Here’s a breakdown of the key changes:
- Specific Bacterial Strains: The EAT employs five specific strains of bacteria, offering a broader detection net compared to the standard test.
- Pre-incubation Method: This method allows for better interaction between the test compound and the bacteria, potentially improving N-nitrosamine detection.
- S9 Fraction: This liver enzyme mixture mimics how the body metabolizes drugs. The EAT requires testing with and without S9 from both rats and hamsters, providing a more comprehensive picture of potential mutagenic effects.
- Fine-tuned Controls: The update emphasizes the use of appropriate negative and positive controls, including specific N-nitrosamines known to be mutagenic, as well as an NDSRI, for a more accurate assessment.
Ongoing Improvements
The EMA acknowledges that N-nitrosamine testing is an evolving field. They emphasize that the EAT recommendations are subject to further refinement as research progresses. The update also provides a checklist for researchers to ensure proper application of the EAT.
Importance of the Update
This update demonstrates the EMA’s ongoing commitment to patient safety. By implementing stricter testing procedures for N-nitrosamine impurities, the agency aims to minimize the risk of exposure to these potentially harmful compounds in medications.
What This Means for Consumers
Consumers can be assured that the EMA is taking proactive steps to ensure the safety of medicines available in the European Union. The updated N-nitrosamine testing recommendations represent a significant improvement in identifying these impurities, further contributing to the safety and quality of medications.
Posted March 2024.
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