Countercurrent staged diafiltration for formulation of high value proteins
Countercurrent staged diafiltration for formulation of high value proteins
复制标题
用于配制高价值蛋白质的逆流分级渗滤
DOI：
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发表时间：
2018
影响因子：
3.8
通讯作者：
A. Zydney
中科院分区：
文献类型：
--
作者：
Anirudh M. K. Nambiar;Y. Li;A. Zydney
许多小组已经研究了连续生物反应器和连续色谱系统的应用，作为开发集成的连续生物制造过程的努力的一部分。本研究的目的是检查使用逆流分级渗滤工艺进行连续蛋白质配制的可行性，同时降低缓冲液要求。使用多克隆免疫球蛋白（IgG）和Cadence™内联浓缩器进行实验。模型方程开发的产品产率，杂质去除，和缓冲液的要求，作为一个功能的阶段的数量和阶段转换（渗透液进料流量比）。来自逆流两阶段系统的数据与模型计算非常一致，证明了使用逆流分级渗滤进行蛋白质配制的潜力。模型模拟证明了逆流分级对缓冲液交换程度和每kg配制产品所需缓冲液量的重要性。分级渗滤工艺不仅提供连续的缓冲液交换，还可以显著减少泵通过次数，同时提供降低缓冲液需求的机会。
A number of groups have studied the application of continuous bioreactors and continuous chromatographic systems as part of efforts to develop an integrated continuous biomanufacturing process. The objective of this study was to examine the feasibility of using a countercurrent staged diafiltration process for continuous protein formulation with reduced buffer requirements. Experiments were performed using a polyclonal immunoglobulin (IgG) with Cadence™ Inline Concentrators. Model equations were developed for the product yield, impurity removal, and buffer requirements as a function of the number of stages and the stage conversion (ratio of permeate to feed flow rate). Data from a countercurrent two‐stage system were in excellent agreement with model calculations, demonstrating the potential of using countercurrent staged diafiltration for protein formulation. Model simulations demonstrated the importance of the countercurrent staging on both the extent of buffer exchange and the amount of buffer required per kg of formulated product. The staged diafiltration process not only provides for continuous buffer exchange, it could also provide significant reductions in the number of pump passes while providing opportunities for reduced buffer requirements.