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 endotoxin from Gram-negative bacteria and non-endotoxin pyrogens (NEP) from Gram-positive bacteria, viruses and fungi. The longstanding compendial test for pyrogens is the rabbit pyrogen test (RPT) 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 RPT. The present study describes the first product-specific GMP validation of Ph. Eur. MAT, Quantitative test, Method A, for the testing of three therapeutic monoclonal antibodies (mAbs). The MAT uses cryo-preserved PBMC with interleukin-6 (IL-6) as the readout. Much of the data presented here for one of the antibodies was included in a successful product licence application to the EMA.

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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. doi: 10.14573/altex.2111301.
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