Medicines and Healthcare Regulatory Agency - National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, UK.
Medicines and Healthcare Regulatory Agency - National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, UK.
Vaccine. 2019 Jun 27;37(29):3761-3769. doi: 10.1016/j.vaccine.2018.05.073. Epub 2018 Dec 10.
The aim of this collaborative study was to evaluate the robustness of the monocyte activation test (MAT) for quantifying the pyrogenic content in the outer membrane vesicle (OMV)-containing vaccine Bexsero: the first meningococcal B vaccine to be licenced. We analysed datasets from 9 laboratories covering 15 test systems for 3 batches of Bexsero with higher, equivalent and lower activity relative to a reference lot in the MAT. Activity was measured in terms of relative pyrogen units (RPU) based on European Pharmacopoeia (Ph. Eur.) MAT Chapter 2.6.30 Method C: Reference Lot Comparison Test. We report that all 15 test systems were consistent in that they showed sample A to be the most active in the MAT; that 13 of 15 test systems had an accuracy of more than 80% and an overall geometric mean RPU of 1.03 with lower and upper 95% confidence limits of 0.97 and 1.09 respectively for a sample with an expected value of 1.00 RPU. We also report larger variability in the results for test systems involving cells from individual blood donations for sample A suggesting that there could be donor to donor differences in sensitivity to the vaccine constituents responsible for the higher activity of this batch. Overall, the consistency and accuracy of the MAT was remarkable given the range of test systems used by participants, all of which are permitted by the Ph. Eur. General MAT Chapter. This is important given the limitations of the rabbit pyrogen test for the control of pyrogenicity in general and particularly with products with intrinsic pyrogenicity such as Bexsero.
这项合作研究的目的是评估单核细胞激活测试（MAT）在定量含外膜囊泡（OMV）疫苗 Bexsero 中发热原含量的稳健性：这是第一个获得许可的脑膜炎 B 疫苗。我们分析了来自 9 个实验室的数据，涵盖了用于 3 批 Bexsero 的 15 个测试系统，这些批次相对于 MAT 中的参考批次具有更高、等效和更低的活性。活性是根据欧洲药典（Ph. Eur.）MAT 第 2.6.30 章 C 节：参考批次比较测试，以相对发热单位（RPU）来衡量。我们报告称，所有 15 个测试系统都一致地表明样品 A 在 MAT 中最活跃；15 个测试系统中有 13 个的准确性超过 80%，总体几何平均 RPU 为 1.03，置信区间下限和上限分别为 0.97 和 1.09，对于预期 RPU 值为 1.00 的样品。我们还报告了涉及单个血液供体样本 A 的测试系统结果的更大变异性，这表明在对导致该批次活性更高的疫苗成分敏感方面，供体之间可能存在差异。总体而言，考虑到参与者使用的测试系统范围广泛，MAT 的一致性和准确性非常显著，所有这些系统都符合 Ph. Eur. 一般 MAT 章节的规定。鉴于兔热原试验在一般情况下控制发热原性的局限性，特别是对于具有内在发热原性的产品（如 Bexsero），这一点非常重要。
