WHO Updates on Nitrosamine Impurities

Nitrosamines in the News
1

Findings from Confirmatory Testing
To-date, confirmatory test results have revealed that certain FPPs formulated with mifepristone, moxifloxacin or ritonavir do contain nitrosamines at levels exceeding acceptable intake limits established according to the Carcinogenic Potency Categorization Approach (CPCA), adopted by regulatory agencies collaborating under the Nitrosamines International Technical Working Group (NITWG).

Interim Measures
Based on benefit-risk considerations, PQT/MED has determined that affected FPP batches may continue to be released under interim acceptable limits, since the risk to the patient associated with interruption of treatment far outweighs any potential future cancer risk associated with nitrosamines present in the products at these levels. These interim limits will remain in place while manufacturers pursue corrective actions or conduct toxicological studies (e.g., enhanced AMES assay tests or other) that may support a higher acceptable intake/limit. PQT/MED will keep monitoring this ongoing work by manufacturers.

2 Likes
2

Hi Yosukemino, Do you know which Interim acceptable limits were accepted for those products (where can I find the information ?) ? LTL approach ? Is a SAR approach can be acceptable for interim limit for these cases ?

3

Dear @PAITREAULT,

Thank you for asking me. However, I am not sure about the WHO’s approaches. Examples of interim limits are described in Appendix 1. The LTL approach appears to be viewed favorably in the document. I am not aware of any examples of the SAR approach being used to set interim limits. Read-across is used to set normal acceptable limits, not interim limits.

4

thank you very much for your feedback !

1 Like