Analytical tools for monitoring changes in physical and chemical properties of chromatography resin upon reuse.
Analytical tools for monitoring changes in physical and chemical properties of chromatography resin upon reuse.
复制标题
用于监测色谱树脂重复使用后物理和化学性质变化的分析工具。
DOI：
10.1002/elps.201900089
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Pathak M
中科院分区：
文献类型：
--
作者：
Pathak M
蛋白A树脂通常重复用于多个循环，以提高mAb纯化过程中的工艺经济性。由于在重复使用时存在沉积在树脂上的不需要的材料（污垢），通常观察到结合能力和产物回收率的显著降低。在本文中，我们已经使用了广泛的定性和定量分析工具（粒度分析，HPLC，荧光，SEM，MS和FTIR），比较不同的分析工具的优点和缺点，他们的能力来检测树脂的污垢，并将其与色谱循环性能。虽然每种工具都可以深入了解这种复杂的现象，但荧光是唯一可用于真实的实时监测树脂结垢的工具。可以在荧光强度和影响树脂重复使用的工艺性能属性（如产率或结合能力）之间建立相关性。该应用荧光进行真实的时间监测的演示与工艺性能属性经验相关，结果支持其作为工艺控制策略的一部分作为PAT工具使用。虽然本文的重点是蛋白A层析树脂的污垢，方法和策略是相关的其他模式的层析以及。
Protein A resins are often reused for multiple cycles to improve process economy during mAb purification. Significant reduction in binding capacity and product recovery are typically observed due to the presence of unwanted materials (foulants) deposited on the resin upon reuse. In this paper, we have used a wide spectrum of qualitative and quantitative analytical tools (particle size analysis, HPLC, fluorescence, SEM, MS, and FTIR) to compare the strengths and shortcomings of different analytical tools in terms of their capability to detect the fouling of the resin and relate it to chromatographic cycle performance. While each tool offers an insight into this complex phenomena, fluorescence is the only one that can be used for real‐time monitoring of resin fouling. A correlation could be established between fluorescence intensity and the process performance attributes (like yield or binding capacity) impacted upon resin reuse. This demonstration of the application of fluorescence for real‐time monitoring correlated empirically with process performance attributes and the results support its use as a PAT tool as part of a process control strategy. While the focus of this paper is on fouling of protein A chromatography resin, the approach and strategy are pertinent to other modes of chromatography as well.