Investigations of prion and virus safety of a new liquid IVIG product
Investigations of prion and virus safety of a new liquid IVIG product
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DOI：
10.1016/j.biologicals.2008.01.004
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发表时间：
2008-07-01
期刊：
影响因子：
1.7
通讯作者：
Kempf, C.
中科院分区：
文献类型：
--
作者：
Stucki, M.;Boschetti, N.;Kempf, C.
最近开发了一种高度纯化的、液体的、用脯氨酸稳定的10%免疫球蛋白产品，称为IgPro 10。通过冷乙醇分级分离、辛酸沉淀和阴离子交换层析从人血浆中纯化IgG。生产工艺包括两个明显不同的分配步骤和病毒过滤，还评估了其对朊病毒的去除。朊病毒去除研究使用不同的加标制剂（脑匀浆、微粒体、纯化的PrPsc）和三种不同的检测方法（生物测定、蛋白质印迹、构象依赖性免疫测定）。所有研究的生产步骤均显示出显著减少了所有不同的加标制剂，导致总体减少> 10 log（10）。此外，生物化学试验证明与生物试验同样有效，可证明朊病毒清除。四个生产步骤涵盖三种不同的病毒清除机制。它们是：i）病毒灭活; ii）病毒过滤;和iii）分配。评估了这些机制的病毒减少能力。病毒验证研究表明，有包膜模型病毒的总体减少因子>18 log（10），无包膜模型病毒的总体减少因子>7 log（10）。总之，IgPro（10）生产工艺对朊病毒和各种病毒具有非常高的减少潜力，从而产生了对已知和新出现病原体安全的最新产品。(C)2008年，国际生物制品协会。由爱思唯尔有限公司出版。保留所有权利。
A highly purified, liquid, 10% immunoglobulin product stabilized with proline, referred to as IgPro10 has recently been developed. IgG was purified from human plasma by cold ethanol fractionation, octanoic acid precipitation and anion-exchange chromatography. The manufacturing process includes two distinctly different partitioning steps and virus filtration, which were also assessed for the removal of prions. Prion removal studies used different spike preparations (brain homogenate, microsomes, purified PrPsc) and three different detection methods (bioassay, Western blot, conformation-dependent immunoassay). All of the investigated production steps were shown to reduce significantly all different spike preparations, resulting in an overall reduction of > 10 log(10). Moreover, the biochemical assays proved equally effective to the bioassay for the demonstration of prion elimination.Four of the manufacturing steps cover three different mechanisms of virus clearance. These are: i) virus inactivation; ii) virus filtration; and iii) partitioning. These mechanisms were assessed for their virus reduction capacity. Virus validation studies demonstrated overall reduction factors of >18 log(10) for enveloped and >7 log(10) for non-enveloped model viruses.In conclusion, the IgPro(10) manufacturing process has a very high reduction potential for prions and for a wide variety of viruses resulting in a state-of-the-art product concerning safety towards known and emerging pathogens. (C) 2008 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.