As previously announced, the nitrosamine impurity, 1-cyclopentyl-4-nitrosopiperazine (CPNP), has been identified in rifapentine products.
Please refer to our previous notes regarding rifapentine.
- https://extranet.who.int/pqweb/news/nitrosamine-concerns-rifapentine-and-rifampicin
- https://extranet.who.int/pqweb/sites/default/files/documents/FAQ_Nitrosamine_18Dec2020.pdf
The WHO Prequalification Unit, Medicines (PQT/MED) has to-date prequalified two rifapentine-based finished pharmaceutical products: Sanofi’s Priftin (TB336) and Macleods Pharmaceutical’s (TB369).
For Priftin (TB336), which is prequalified based on USFDA approval, Sanofi has continued providing regular updates to PQT/MED. Given the critical role this medicine plays in public health, the USFDA continues to permit the temporary distribution of Priftin tablets with CPNP impurity content at or below 20 parts per million (ppm), while the manufacturer works on possible corrective measures.
In May 2022, PQT/MED prequalified the first isoniazid/rifapentine generic product (TB369 - Isoniazid/Rifapentine - 300mg/300mg - Film-coated tablet - Macleods Pharmaceuticals Ltd) with an interim release limit of NMT 20 ppm for CPNP impurity, established based on risk-benefit considerations and process capability. The interim limit will be reviewed regularly.
Similarly, WHOAPI-375 (rifapentine API from Macleods Pharmaceuticals Ltd) has been accepted with an interim release limit for CPNP based on process capability.
PQT/MED is closely working with the manufacturers on mitigation measures that should be applied in order to decrease the impurity content to lifetime acceptable levels. Such mitigation measures require investigations and time so that they can be verified as effective.
PQT/MED is closely monitoring the issue of nitrosamine impurities and the ongoing work by manufacturers and other regulators. A field sampling and testing study is also planned.
For further information please contact: Dr Matthias Stahl at stahlm@who.int