Application of the Monocyte Activation Test for Medical Device Pyrogen Testing

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, 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. To review MAT and discuss ongoing challenges to its widespread implementation for medical device testing, NICEATM and the PETA Science Consortium International e.V. co-organized a September 2018 workshop. A workshop report has been published in ALTEX (Brown et al. 2021).

Workshop participants explored how the FDA Medical Device Development Tools Program could be used to qualify MAT as a standalone pyrogen test for specific medical device contexts of use. Attendees discussed practical aspects of pyrogen testing and the evidence needed to support qualification of MAT as a replacement for animal-based pyrogen tests. There was general agreement that 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 material-mediated pyrogens. This testing would determine whether the assay can be used for both biocompatibility and sterility or if other information on material-mediated pyrogens would be needed to address biocompatibility. Participants also discussed information gaps on material-mediated pyrogens, potential test controls, and other challenges and opportunities for implementing the use of MAT as a comprehensive pyrogen test.