The Monocyte Activation Test (MAT), described in EP 2.6.30, is an advanced in vitro assay for pyrogen detection. Unlike traditional rabbit pyrogen testing, MAT detects a wide range of pyrogens using human immune cells, offering higher sensitivity and improved relevance to human physiology. It also supports 3R principles (Replacement, Reduction, Refinement) by reducing animal testing, making it both a regulatory-accepted and ethical alternative.