Daniels Ruth, Van der Elst Wim, K So Chi, Voeten Liesbeth, Breugelmans Philip, Molenaar-de Backer Marijke W A, Poole Stephen, Patel Mehul
Analytical Development Microbiology CoE, Janssen Pharmaceutica NV (a Johnson and Johnson Company), Turnhoutseweg 30, 2340 Beerse, Belgium.
Statistics and Decision Sciences, Janssen Pharmaceutica NV (a Johnson and Johnson Company), Turnhoutseweg 30, 2340 Beerse, Belgium.
Curr Res Toxicol. 2024 Dec 12;8:100206. doi: 10.1016/j.crtox.2024.100206. eCollection 2025.
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.
本研究描述了用于检测热原性和促炎污染物的单核细胞活化试验（MAT）的“适用性”测试以及针对该产品的独立GMP验证，即MAT方法A，定量试验（欧洲药典，Ph. Eur. 第2.6.30章，2017年）。开展了一项适用性研究，以确保所选的MAT设置（冷冻保存的外周血单核细胞，IL-6检测）能够可靠地区分含有低于污染物限度浓度（CLC）的热原性污染物的产品批次与含有高于CLC的热原性污染物的产品批次。在将所选的MAT设置用于后续产品检测之前，进行一次这样的测试，以表明假阳性（热原阴性（<CLC）批次检测为热原阳性（>CLC）批次）尤其是假阴性（热原阳性（>CLC）检测为热原阴性（<CLC））的发生率较低。本研究还提供了一个机会，收集一组独立的验证数据，以便与之前获得的数据（Daniels等人，2022年）进行比较，以评估MAT方法A的稳健性及其在尚未取代兔热原试验（RPT）的情况下取代该试验的适用性。
