Fit for purpose testing and independent GMP validation of the monocyte activation test.

The present study describes the "fit for purpose" testing and the independent product-specific GMP validation of the monocyte activation test (MAT) to detect pyrogenic and pro-inflammatory contaminants, MAT Method A, Quantitative Test (European Pharmacopoeia, Ph. Eur. chapter 2.6.30, 2017). A fit for purpose study was carried out to ensure that the chosen MAT set-up (cryopreserved PBMC, IL-6 detection) can reliably discriminate between batches of product containing pyrogenic contaminants below the contaminants limit concentration, CLC, from batches containing pyrogenic contaminants above the CLC. Such testing is carried out once, before the chosen MAT set-up is used for subsequent product testing to show that the incidence of false positives (pyrogen-negative (<CLC) batches testing as pyrogen-positive (>CLC) batches) and - especially - false negatives (pyrogen-positive (>CLC) testing as pyrogen-negative (<CLC)) is low. This study also afforded the opportunity to collect an independent body of validation data for comparison with that obtained previously (Daniels et al., 2022) to evaluate the robustness of MAT Method A and its fitness to replace the rabbit pyrogen test (RPT) where this has not already happened.