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Monocyte Activation Test (MAT) for Pyrogen Detection


MAT Enables Animal-Free Detection of a Broad
Spectrum of Pyrogens

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In the pharmaceutical industry, pyrogen detection is mandatory to avoid the life-threatening fever reactions that can be induced by both microbial and non-microbial substances. The Monocyte Activation Test (MAT) was introduced into the European Pharmacopeia (EP) in 2010 following publications of international validations. This test was developed as an alternative to animal-based methods and was aimed at offering the opportunity to perform pyrogen testing in a human in vitro system.

Pyrogens…a hot story!

Monocyte Activation Test (MAT) in vitro test kits for pyrogen detection: a real game-changer

The first fever-causing agents, “pyrogens”, were identified in 1912 by Hort and Penfold, who designed a pyrogen test based on injection of material into rabbits. The required high number of pyrogen tests on rabbits and the variable sensitivity of that test system made the development of alternative tests highly necessary. The in vitro Monocyte Activation Test for pyrogen detection offers a valuable alternative to the rabbit test. It produces results that are both reliable and reproducible, which are essential for quality assurance.

MAT Key Benefits

  • In vivo method using human blood or monocytic cell line
    • Mimics the human innate immune response to a fever reaction caused by pyrogens
    • Promoted by regulation since introduction into EP and in FDA guidance for industry
  • Patient safety: detection of both Endotoxins and Non-Endotoxin Pyrogens (NEPs)
  • High level of reliability
    • Includes both a positive and a negative control
    • In vitro test: easy to perform
    • High level of sensitivity

Merck provides two MAT systems for the detection of a broad spectrum of Pyrogens:

PyroDetect System


Based on cryopreserved human whole blood and IL1β read-out.
PyroMAT™ System


Based on the Mono-Mac-6 cell line and IL-6 read-out.

Comparison of Pyrogen Test Methods

Test Type In vivo Ex vivo In vitro (Cryopreserved
whole blood)
In vitro (Monocytic
cell line)
Animal Consumption ++ + - -
Contaminant Detection Gram-negative (LPS) + + + +
Gram-positive (LTA) + - + +
Yeasts & Molds + - + +
Viruses +/- - + +
Pharmaceuticals + + + +
Biologicals + +/- + +
Medical devices + +/- + +
Cell therapeutics - +/- + +
Table 1: Comparison of pyrogen test methods