Saturday, 18 February 2023 17:50

Monocyte Activation Test: Revision of the European Pharmacopoeia Featured

The European Directorate for the Quality of Medicines (EDQM) has published 59 amended texts in the European Pharmacopoeia (Ph. Eur.) concerning the rabbit pyrogenicity test for public consultation. The goal is to replace the rabbit test with an in vitro alternative.

The monocyte activation test (MAT) uses an innate human immune response to so-called pyrogens, bacterial substances such as cell wall fragments, yeast, fungal or viral particles. As foreign bodies, they trigger a defensive reaction in the body, which is associated with a fever response.

Instead of the rabbit, which had not always reliably indicated the fever reaction in all cases, the MAT or another test should now be used instead. In MAT, white blood cells (monocytes/macrophages) secrete so-called proinflammatory cytokines such as interleukin 1ß (IL-1ß) in response to pyrogens, it is most suitable as a detection. An antibody is subsequently bound to the IL-1ß, which can be visualized by means of a color reaction. The pyrogenic contamination can now be determined.(1)

The test detects a more comprehensive pyrogen spectrum like the rabbit test and a much broader one than the Limulus amoebocyte lysate (LAL) test, with which only lipopolysaccharides of Gram-negative bacteria (endotoxins) can be detected to a limited extent. This test utilizes a proenzyme from amebocytes (2) of blood from the horseshoe crab (Limulus polyphemus).

The texts amended in the European Pharmacopoeia cover a wide range of topics, including vaccines for human use, blood products, antibiotics, radiopharmaceuticals as well as containers. The full replacement of the rabbit test is expected to take place within the next three years.

Stakeholders are being asked to comment on this by March 31, 2023.

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