Design and optimization of Single Pass Tangential Flow Filtration for inline concentration of monoclonal antibodies
Design and optimization of Single Pass Tangential Flow Filtration for inline concentration of monoclonal antibodies
复制标题
用于在线浓缩单克隆抗体的单通道切向流过滤的设计和优化
DOI：
10.1016/j.memsci.2021.120047
复制
发表时间：
2022
影响因子：
9.5
通讯作者：
Zydney, Andrew L.
中科院分区：
文献类型：
--
作者：
Jabra, Mario G.;Zydney, Andrew L.
许多单通道切向流过滤（SPTFF）系统最近已经商业化，用于单克隆抗体和其他生物治疗药物的在线浓缩，既可以解决现有工艺中的瓶颈，也可以作为集成连续下游工艺发展的一部分。本研究的目的是利用先前开发的滤液通量和压降数学模型来检验SPTFF模块的设计和优化，该模型特别考虑了抗体粘度和渗透压的浓度依赖性，以及流速和抗体浓度随长路径SPTFF装置位置的变化。进行模型模拟以检查通道宽度、长度和卡带分级（每个分级中并行卡带的数量）对SPTFF性能的影响。狭长的通道配置的浓度因子（转化率）最大，但这也会导致非常大的进料侧压降。使用叶栅结构，在进料口附近有更多的平行通道，显著降低了压降，但相应的增加了总膜面积。控制SPTFF性能的一个关键因素是高转化率时抗体溶液粘度的增加。这些结果为单克隆抗体处理SPTFF系统的设计和优化提供了重要的见解。
A number of Single Pass Tangential Flow Filtration (SPTFF) systems have recently been commercialized for inline concentration of monoclonal antibodies and other biotherapeutics, both to resolve bottlenecks in existing processes and as part of the development of integrated continuous downstream processes. The objective of this study was to examine the design and optimization of SPTFF modules using a previously developed mathematical model for the filtrate flux and pressure drop that specifically accounts for the concentration dependence of the antibody viscosity and osmotic pressure as well as the variation of the flow rate and antibody concentration with the position in the long pathlength SPTFF device. Model simulations were performed to examine the effects of channel width, length, and cassette staging (number of parallel cassettes in each stage) on SPTFF performance. The concentration factor (conversion) was greatest for a long thin channel configuration, but this also caused very large feed-side pressure drops. The use of cascade configurations, with a greater number of parallel channels near the feed inlet, significantly reduced the pressure drop but with a corresponding increase in total membrane area. A key factor governing the SPTFF performance was the increase in viscosity of the antibody solution at high conversion. These results provide important insights into the design and optimization of SPTFF systems for monoclonal antibody processing.
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