Trejo S R, Hotta J A, Lebing W, Stenland C, Storms R E, Lee D C, Li H, Petteway S, Remington K M
Pre-Clinical Research and Pathogen Safety, Bayer Healthcare, Biological Products Division, Research Triangle Park, North Carolina, USA.
Vox Sang. 2003 Apr;84(3):176-87. doi: 10.1046/j.1423-0410.2003.00279.x.
Minimizing the transmission risk of infectious diseases is of primary importance in the manufacture of products derived from human plasma. A novel chromatography-based intravenous immunoglobulin (IGIV) manufacturing process was developed and the reduction of virus and transmissible spongiform encephalopathies (TSE) during the manufacturing process was assessed. Mechanistically distinct steps that could affect virus reduction were identified, and the robustness of virus reduction over the range of process conditions was determined.
Virus and TSE reduction by processing steps were assessed using a scaled-down version of the IGIV manufacturing process.
Virus and TSE reduction at manufacturing process set points were well within safety standards. Robustness studies verified that the reproducibility of virus reduction was maintained at or beyond operating parameter extremes. Virus reduction across two combined manufacturing steps was lower than the sum of virus-reduction values across the individual steps, indicating mechanistic similarity of the two steps with respect to virus reduction. Only reduction from mechanistically distinct steps was claimed.
This comprehensive approach to pathogen safety provides the new immunoglobulin manufacturing process with a detailed, yet realistic, assessment of the risk of transmission of infectious pathogens.
在源自人血浆的产品生产过程中，将传染病传播风险降至最低至关重要。研发了一种基于色谱法的静脉注射免疫球蛋白（IGIV）生产工艺，并评估了生产过程中病毒及传染性海绵状脑病（TSE）的减少情况。确定了可能影响病毒减少的机制不同的步骤，并测定了在一系列工艺条件下病毒减少的稳健性。
使用IGIV生产工艺的缩小版本评估各加工步骤对病毒和TSE的减少情况。
生产过程设定点处的病毒和TSE减少量完全符合安全标准。稳健性研究证实，在操作参数极限或超出极限的情况下，病毒减少的可重复性得以维持。两个联合生产步骤的病毒减少量低于各单个步骤病毒减少值之和，表明这两个步骤在病毒减少方面机制相似。仅声称来自机制不同步骤的减少量。
这种针对病原体安全性的综合方法为新的免疫球蛋白生产工艺提供了对传染性病原体传播风险的详细而现实的评估。
