Validation of the monocyte activation test with three therapeutic monoclonal antibodies

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Ruth Daniels
Wim Van der Elst
Nele Dieltjens
Tinne Appels
Chi K. So
Thomas Nys
Liesbeth Voeten
Philip Breugelmans
Marijke W. A. Molenaar-de Backer
Eelo Gitz
Stephen Poole
Mehul Patel

Abstract

Pharmaceutical products intended for parenteral use must be free from pyrogenic (fever-inducing) contamination. Pyrogens comprise endotoxins from Gram-negative bacteria and non-endotoxin pyrogens from Gram-positive bacteria, viruses, and fungi. The longstanding compendial test for pyrogens is the rabbit pyrogen test, but in 2010 the monocyte activation test (MAT) for pyrogenic and pro-inflammatory contaminants was introduced into the European Pharmacopoeia (Ph. Eur.) as a non-animal replacement for the rabbit pyrogen test. The present study describes the first product-specific Good Manufacturing Practice validation of Ph. Eur. MAT, Quantitative Test, Method A for the testing of three therapeutic monoclonal antibodies. The study used the MAT version with cryo-preserved peripheral blood mononuclear cells and interleukin-6 as the readout. Much of the data presented here for one of the antibodies was included in a successful product license application to the European Medicines Agency.

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How to Cite
Daniels, R., Van der Elst, W., Dieltjens, N., Appels, T., So, C. K., Nys, T., Voeten, L., Breugelmans, P., Molenaar-de Backer, M. W. A., Gitz, E., Poole, S. and Patel, M. (2022) “Validation of the monocyte activation test with three therapeutic monoclonal antibodies”, ALTEX - Alternatives to animal experimentation, 39(4), pp. 621–635. doi: 10.14573/altex.2111301.
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