A nitrosamine impurity, 1-methyl-4-nitrosopiperazine (MeNP), was identified in rifampicin products.
In September 2020, PQT requested all rifampicin API and medicines applicants to test MeNP impurity in a representative number of batches.
Please refer to our previous notes regarding rifampicin in:
- /prequal/news/nitrosamine-concerns-rifapentine-and-rifampicin
- /prequal/sites/default/files/document_files/FAQ_Nitrosamine_18Dec2020.pdf
The results provided for all prequalified APIs and Finished Pharmaceutical Products (FPP) show that MeNP is present at trace levels in all batches tested. MeNP levels have been shown to be below or close to 5 ppm in all API and FPP products tested. PQT/MED has assessed the related nitrosamines risk quality information for all prequalified rifampicin products (APIs and FPPs) taking into consideration toxicological and risk/benefit balance assessments.
For all prequalified APIs, interim limits for MeNP impurity have been accepted on a temporary basis. These interim limits have been defined based on process capability on a case-by-case and will be reviewed regularly. Similarly, interim limits are being assessed for the prequalified FPPs.
PQT/MED is closely working with the manufacturers to follow up on mitigation measures that should be applied in order to decrease the impurity to lifetime acceptable levels. Mitigation measures may require investigations and time until they can be verified as effective.
PQT/MED has concluded that the risk to the patient associated with interruption of treatment far outweighs any potential future cancer risk associated with MeNP impurity present in the products at this level. Therefore, the PQT/MED’s recommendation not to interrupt any rifampicin treatment remains.
PQT/MED keeps closely monitoring the responses related to rifampicin products and the ongoing work by manufacturers. A field sampling and testing study is also planned.