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 acti-vation 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.