Nitrosamine concerns for Rifapentine

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Update on Nitrosamine Impurity found in TB Drug Rifapentine

In quarter 2 2020, a notice was sent that a nitrosamine impurity, 1-cyclopentyl-4-nitrosopiperazine (CPNP), detected in Priftin® 150mg tablets manufactured by Sanofi. At that time, health care professionals treating patients with latent tuberculosis infections were advised not to begin new patients on Priftin® until further notice. Since then, a benefit-risk assessment was conducted and batches of Priftin® over the limit was removed.

The CPNP impurity levels range from 12 ppm to 25 ppm. These levels exceed the acceptable concentration limit of 0.11 ppm. At WHO PQT request, Sanofi has committed to test lots prior to release and to further test lots currently on the market. The interim limit of ≤20 ppm at release, and ≤ 25 ppm at the end of shelf life, is in effect until Sanofi can reduce CPNP in Priftin to within the acceptable limit of ≤ 0.11 ppm. The IMPAACT4TB Consortium has put measures in place to monitor progress closely and expects Sanofi to make every necessary effort to reduce the level of the impurity to at, or below, the acceptable concentration limit of 0.11 ppm as soon as possible.

Rifapentine API impurity ADULTS

  • All batches of rifapentine released by Sanofi and Macleods will be tested to ensure the drug product meets the CPNP temporary limit of 20 ppm  as accepted by the FDA and recognized by the WHO PQT/MED
  • Sanofi resumed production in Dec 2020 at the same time Macleods received clearance of FDC 3HP from Global Fund ERP. All of these batches will clear the CPNP limits sent with testing documentation
  • Suppliers will do additional testing for CPNP (and MNP) impurities and plan to reduce levels to 0.1ppm CPNP. This may increase the price of products.

Rifapentine API impurity Pediatric

  • March 2021 CPNP assay results for the water-dispersible rifapentine formulations show product is well below 20ppm interim limit.
  • Certificates of analyses approved levels of RPT trial dosage for children under TBTC35
  • RPT for kids expected to begin production in to replace trial FDC but GLOBAL recommendation to move forward with 150mg single dispersible. (PADO, GAP-F)