MAT for Medical Devices
MAT is the most comprehensive assay for testing medical devices
Testing medical devices for all pyrogens is a must
Medical devices manufactured for implantation into humans must be free of pyrogens. Pyrogenic contaminants on the surface of medical devices are very often not soluble.
BET and RPT test only rinsing solutions of products
BET and RPT fail to detect non-soluble pyrogens as these assays test only the rinsing solutions of products. These don’t reflect the entire surface contamination, which causes false negative results.
MAT captures all contaminations by direct incubation
Only MAT for medical devices tests by direct incubation with human blood cells, which captures contaminants on a device’s entire surface – making it the most comprehensive pyrogen test.
How would testing your medical device using MAT work?
MAT employs peripheral blood mononuclear cells to simulate the first stages of a human’s immunological response to a medical device’s contamination of pyrogens.
(1) Direct incubation of the device
Your parenteral medical device is (where necessary, dynamically) incubated with peripheral blood mononuclear cells.
(2) Immunological activation
Left overnight, Toll-like receptors of monocytes detect any pyrogens, which will then launch the human immune system. The release of cytokines is activated.
(3) Cytokine detection
The next morning, detection and quantification of released IL-6 cytokine concentration is established by carrying out a human IL-6 ELISA.
(4) Analysis of data
The concentration of cytokines in the medical device preparation is then converted into Endotoxin Equivalent units/ml using the LPS standard curve.
Regulatory bodies on the suitability of MAT for medical devices
The European Pharmacopoeia
- Ph. Eur. 2.6.8 Pyrogens: Recommendations to use MAT (2.6.30) as a replacement to Rabbit Pyrogen Test wherever possible.
- Ph. Eur. 2.6.30 Monocyte Activation Test: “The monocyte Activation Test (MAT) is primarily intended to be used as a replacement for the Rabbit Pyrogen Test.”
- Ph. Eur. 5.1.10: “The Monocyte Activation Test (2.6.30) is a suitable method to rule out the presence of non-endotoxin pyrogens in substances or products”.
The US Food and Drug Association
- In 2009, noted that the Monocyte Activation Test (MAT) may be used for parenteral products once product-specific validation (PSV) has been carried out.
- See Dr. Norris Alderson’s response (FDA Associate Commissioner for Science)
- 2012’s Guidance for industry pyrogen and endotoxins testing allows MAT to be employed as LAL replacement for medical devices using PSV.
- See Guidance for industry pyrogen and endotoxins: Questions and answers (2012)
The International Organization for Standardization (ISO)
- ISO 10993-1:2018 explicitly expresses their preference for in-vitro rather than in-vivo models whenever they have been found to deliver information of equivalent relevance.
- Further info on ISO’s stance on pyrogen testing is detailed in ISO 10993-11:2017.