Monocyte Activation Testing (MAT) medical devices
Just like parenteral drugs, medical devices manufactured for human implantation must be free of pyrogens. The Monocyte Activation Test is the first assay capable of testing medical devices by direct incubation – making it the most secure pyrogen test out there.
By law medical devices manufactured for implantation into humans must be free of pyrogens. When pyrogencially contaminated, contact of implanted medical devices with human tissue or blood can result in different degrees of inflammation, sometimes leading to serious health problems.
The Monocyte Activation Test succeeds as a pyrogenicity assay for blood transfusion products and medical devices – where RPT and LAL have proven either problematic or insufficient. MAT is suited for the detection of pyrogens on the surface of medical devices as these contaminants are frequently not soluble, and thus cannot be detected by rinsing the device, though when in a patient, they may cause adverse reactions. The LAL and RPT are only suitable for testing rinsing solutions that do not reflect the entire surface contamination, causing false negative results. Only MAT is able to test the device by direct incubation with human blood cells – making it the safest pyrogen test out there for pharmaceutical products and medical devices.
EP and FDA approved.
Regulatory acceptance on Monocyte Activation Testing
The FDA issued a guideline in 2012 allowing the MAT test to be used as a replacement for the LAL for testing medical devices after product-specific validation (US FDA, 2012). Furthermore, general Chapter <151> of the United States Pharmacopeia (USP) on pyrogens allows using a validated equivalent in vitro pyrogen or bacterial endotoxin test, to replace the RPT (USP, 2017). However, ISO 10993-1: 2018's preference for an in vitro pyrogen test reinforced regulatory acceptance of MAT over animal testing when they provide equally relevant information.
The MAT was integrated in the European Pharmacopoeia’s general chapter, Monocyte Activation Test, 2.6.30, stating the MAT as a full replacement for the RPT after product-specific validation (EDQM, 2010).
The MAT has been accepted into the U.S. FDA's Medical Device Development Tools (MDDT) program and is currently under review to qualify as a stand-alone medical device release test that can replace the use of the RPT and BET/LAL when meet the requirements for biocompatibility and sterility testing.
Testing medical devices starts with interference testing, comparable to pharmaceuticals according to the European Pharmacopeia protocol. The process of interference testing involves spiking the device with a defined amount of LPS and then testing both the spiked and non-spiked devices together with an LPS standard curve. The mean recovery of the spiked endotoxin equivalent will then be determined using the LPS standard curve which must be between 50% to 200%.
Monocyte Activation Testing medical devices
Monocyte Activation Testing and material mediated pyrogenicity
To exclude the possibility that the device's material interferes with the test there are two depyrogenation methods: Dry heat treatment and Sodium Hydroxide treatment. If the pyrogenicity of an unspiked device remains after depyrogenation, it is related to material-mediated pyrogenicity. This should be confirmed by showing that the depyrogenation is capable of removing the spiked LPS on the same device.
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