Increasing Parvovirus Filter Throughput of Monoclonal Antibodies Using Ion Exchange Membrane Adsorptive Pre-filtration
Increasing Parvovirus Filter Throughput of Monoclonal Antibodies Using Ion Exchange Membrane Adsorptive Pre-filtration
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DOI：
10.1002/bit.22729
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发表时间：
2010-07-01
影响因子：
3.8
通讯作者：
Dowd, Chris
中科院分区：
文献类型：
--
作者：
Brown, Arick;Bechtel, Charity;Dowd, Chris
使用离子交换膜吸附器的预过滤可以提高单克隆抗体（mAb）的细小病毒膜通量。膜通过结合痕量污染物而起作用，并且尽管一些抗体产物也结合，但是通过兽医加载容易实现产率>= 99%。结果表明，污垢吸附取决于pH和电导率，但与规模和吸附剂品牌无关。使用离子交换膜作为预过滤器的能力是重要的，因为它提供了一种清洁的、明确定义的、化学稳定的选择，以提高通量。离子交换膜有助于细小病毒过滤器污垢的表征使用沉降速度分析和SEC-MALS/QELS显示存在流体动力学半径范围为8 - 13 nm的高分子量物质，其大小与细小病毒相似，因此预计会堵塞细小病毒过滤器的孔。两个相同的膜串联的研究支持这一假设，即污物是可溶的，痕量水平的聚集体在饲料中。这项研究的意义在于膜色谱法的一个以前未发现的应用，导致一个更具成本效益和鲁棒性的方法来细小病毒过滤生产单克隆抗体。生物技术与生物工程2010，106. 627-637. (C)2010 Wiley Periodicals，Inc.
Pre-filtration using ion exchange membrane adsorbers can improve parvovirus film throughput of monoclonal antibodies (mAbs) The membranes work by binding trace foulants, and although some antibody product also binds, yields >= 99% ale easily achieved by vet loading. Results show that foulant adsorption is dependent on pH and conductivity, but independent of scale and adsorber brand The ability to use ion exchange membranes as pre-filters is significant because It provides a clean, well defined, chemically stable option for enhancing throughput Additionally, ion exchange membranes facilitate characterization of parvovirus filter foulants Examination of adsorber elution samples using sedimentation velocity analysis and SEC-MALS/QELS revealed the presence of high molecular weight species ranging from 8 to 13 nm in hydrodynamic radius, which are similar in size to parvoviruses and thus would be expected to plug the pores of a parvovirus filter. A study of two identical membranes in-series supports the hypothesis that the foulants are soluble, trace level aggregates in the feed This study's significance lies in a previously undiscovered application of membrane chromatography, leading to a more cost effective and robust approach to parvovirus filtration for the production of monoclonal antibodies. Biotechnol Bioeng 2010,106. 627-637. (C) 2010 Wiley Periodicals, Inc.