An optimization study of an integrated periodic counter-current chromatography (PCC) process in a monoclonal antibody (mAb) downstream process at lab scale, is presented in this paper. The optimization was based on a mechanistic model of the breakthrough curve in the protein-A capture step. Productivity and resin utilization were the objective functions, while yield during the loading of the capture column was set as a constraint. Different integration approaches were considered, and the effect of the feed concentration, yield and the protein-A resin was studied. The breakthrough curve and the length of the product recovery, which depended on the integration approach, determined the process scheduling. Several optimal Pareto solutions were obtained. At 0.5 mg mL-1 and 99% yield, a maximum productivity of 0.38 mg mL-1 min-1 with a resin utilization of 60% was obtained. On the other hand, the maximum resin utilization was 95% with a productivity of 0.10 mg mL-1 min-1. Due to the constraint of the process scheduling, a lower productivity could be achieved in the integration approaches with higher recovery time, which was more remarkable at higher concentrations. Therefore, it was shown that a holistic approach, where all the purification steps are considered in the process optimization, is needed to design a PCC in a downstream process.

中文翻译：

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整合在单克隆抗体下游工艺中的周期性逆流色谱的优化研究。

本文介绍了实验室规模的单克隆抗体（mAb）下游工艺中的集成定期逆流色谱（PCC）工艺的优化研究。优化基于蛋白质A捕获步骤中突破曲线的机械模型。生产率和树脂利用率是目标函数，而捕获塔上样时的收率则被设置为约束条件。考虑了不同的整合方法，并研究了进料浓度，收率和A蛋白树脂的影响。突破曲线和产品回收的时间长短取决于集成方法，决定了工艺调度。获得了几种最佳的帕累托解。在0.5 mg mL-1和99％的产率下，最大生产率为0。获得38 mg mL-1 min-1，树脂利用率为60％。另一方面，最大树脂利用率为95％，生产率为0.10 mg mL-1 min-1。由于工艺调度的限制，在集成方法中可以实现较低的生产率，同时具有较高的恢复时间，这在较高的浓度下更为显着。因此，表明需要一种整体方法，其中在工艺优化中考虑了所有纯化步骤，以在下游工艺中设计PCC。