A workshop on September 18-19 at NIH explored challenges to acceptance of a human cell-based assay for pyrogen testing of medical devices. The workshop was organized by NICEATM and the PETA International Science Consortium.
Pyrogens are substances that can produce fever when present as contaminants in a drug or medical device. Most pyrogens are biological substances derived from bacteria, fungi, and viruses; material-mediated pyrogens (MMPs), while less common, may also be present. Drugs for injection and medical device products for implantation or other systemic exposure should meet pyrogen limit specifications before they are marketed. Animal-based pyrogen tests are often conducted to investigate the presence of pyrogens. Non-animal monocyte activation tests (MAT) are widely available but infrequently used for pyrogen testing.
At the September workshop, regulators, test developers, medical device manufacturers, and other experts explored how the U.S. Food and Drug Administration Medical Device Development Tools Program could be used to qualify the use of MAT as a standalone pyrogen test for specific medical device contexts-of-use. There was general agreement that the MAT could be qualified as acceptable for batch-release testing for microbial-based pyrogens. However, additional studies were recommended to demonstrate its ability to detect known MMPs. This testing would determine whether the assay can be used for both biocompatibility and sterility or if other information on MMPs would be needed to address biocompatibility.
More information about NICEATM and ICCVAM evaluation of pyrogen test methods is available at https://ntp.niehs.nih.gov/go/iccvam-pyrogen. An agenda, presentations, and other materials from the meeting are available at https://www.piscltd.org.uk/medical-device-pyrogen/.