Nitrosamine impurities have been identified in rifapentine and rifampicin products.
WHO Prequalification Unit - Medicines Assessment Team (PQT/MED) has been in contact with Sanofi regarding the presence of 1-cyclopentyl-4-nitrosopiperazine (CPNP) in their tuberculosis treatment - Priftin (Rifapentine). PQT/MED prequalified this medicine as TB336, based on SRA approval. In this instance, prequalification was based upon the registration of this product with the USFDA. As per their notification dated 26 August 2020, USFDA will not object to the temporary distribution of rifapentine containing CPNP below 14 ppm. PQT/MED recognises the USFDA decision for this product. Sanofi is providing regular updates to PQT/MED on this matter.
Another nitrosamine impurity, 1-methyl-4-nitrosopiperazine (MeNP), has been identified in rifampicin products. PQT/MED has requested all API and medicines applicants to test the nitrosamine impurity in a representative number of batches. Once actual levels for each concerned product are available, PQT/MED will take decisions on a case-by-case basis, taking into consideration toxicological and risk/benefit balance assessments. PQT/MED recommends not to interrupt any rifampicin treatment and not to take any action until conclusions are made.
Last April PQT/MED called for review on nitrosamines for all API and medicines applications. Companies are advised to conduct risk assessments to evaluate the potential for the presence of nitrosamine impurities in a timely manner.
PQT/MED continues to assess the information on nitrosamine impurities and their associated risk.