The Monocyte Activation Test (MAT), also known as the Human Cell-Based Pyrogen Test (HCPT) in ISO/TR 21582, is an in vitro assay based on the response of human cells to pyrogens that may be bacterial endotoxins or non-endotoxin pyrogens. Specifically, the test utilises
the release of cytokines from monocytes or monocytic cell lines that indicate the presence of pyrogenic contaminants.
This technique offers various advantages over the more traditional Bacterial Endotoxin Test (BET) and Rabbit Pyrogen Test (RPT). Indeed, BET is limited by the fact that it can only detect endotoxins while RPT carries several drawbacks such as poor robustness, the potential for differing immune responses between rabbits and humans, the inability to test various products including chemotherapeutics, immunosuppressive agents, and human cellular preparations. Moreover, both methods present ethical problems related to animal testing.
During the MAT, the sample is tested in appropriate dilutions, both with and without added endotoxin. The response, in terms of cytokine production, is compared to an endotoxin standard curve. Non-endotoxin pyrogens may be run in parallel, and the choice of the appropriate molecule should be based on the manufacturing process and microbiological data.
Although MAT is widely accepted in Europe for pharmaceutical products, this technique is considered by the FDA as an alternative method and its validation is therefore required.
In the medical device field, MAT is specifically discussed in ISO/TR 21582. This standard addresses the issue of material-mediated pyrogens (MMP) and defines the RPT as the only test capable of detecting such materials. Consequently, medical devices must still be tested for MMP to gain regulatory approval.
However, this topic is currently being debated, as MMPs are rarely found in medical devices, and their role and mechanism remain largely unclear.
Further insights into MMPs may be provided by the updated version of ISO 10993-1, which is currently in the drafting phase.