Dear Medical Device Manufacturers:
The U.S. Food and Drug Administration (FDA), through the Center for Devices and Radiological Health (CDRH), is issuing this letter to provide manufacturers of CDRH-led combination products with information related to potential nitrosamine impurities. This letter describes manufacturer responsibilities and highlights resources that may assist in identifying and managing potential nitrosamine impurities in these products.
Background
Nitrosamine exposure above acceptable levels over long periods of time may increase the risk of cancer. CDRH has been investigating the potential presence of nitrosamine impurities in CDRH-led combination products. As part of this ongoing work, CDRH has become aware that 1-methyl-4-nitrosopiperazine (MNP), a nitrosamine drug substance–related impurity (NDSRI), has been detected in certain CDRH-led combination products containing the drug rifampin. At this time, CDRH is not aware of adverse events associated with nitrosamine exposure from CDRH-led combination products.
Potential sources of nitrosamines in CDRH-led combination products may include the drug product itself or the manufacturing process for the finished combination product. Manufacturers are responsible for understanding the risks of any impurities, including nitrosamines, that may be present in their final products as part of their overall biocompatibility/risk assessment.