Continuous capture with affinity chromatography is one of the most important units for continuous manufacturing of monoclonal antibody (mAb). Due to the complexity of three-column periodic counter-current chromatography (3C-PCC), three approaches (experimental, model-based, and simplified approaches) were studied for process development and optimization. The effects of residence time for interconnected load (RT _C), breakthrough percentage of the first column for interconnected load (s) and feed protein concentration (c ₀) on productivity and capacity utilization were focused. The model-based approach was found superior to the experimental approach in process optimization and evaluation. Two phases of productivity were observed and the optimal RT _C for the maximum productivity was located at the boundary of the two phases. The comprehensive effects of the operating parameters (RT _C, s, and c ₀) were evaluated by the model-based approach, and the operation space was predicted. The best performance of 34.5 g/L/h productivity and 97.6% capacity utilization were attained for MabSelect SuRe LX resin under 5 g/L concentration at RT _C = 2.8 min and s = 87.5%. Moreover, a simplified approach was suggested to obtain the optimal RT _C for the maximum productivity. The results demonstrated that model-assisted tools are useful to determine the optimum conditions for 3C-PCC continuous capture with high productivity and capacity utilization.

中文翻译：

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三柱周期性逆流色谱连续捕获工艺开发与优化

亲和层析连续捕获是连续生产单克隆抗体 (mAb) 的最重要单元之一。由于三柱周期性逆流色谱 (3C-PCC) 的复杂性，研究了三种方法（实验方法、基于模型的方法和简化方法）用于工艺开发和优化。互连负载的停留时间 ( RT _C )、互连负载的第一柱穿透百分比 ( s ) 和进料蛋白质浓度 ( c _{0 ) 的影响}) 的重点是生产力和产能利用率。发现基于模型的方法在工艺优化和评估方面优于实验方法。观察到生产力的两个阶段，最大生产力的最佳RT _C位于两个阶段的边界。采用基于模型的方法评价运行参数（RT _C、s和c _{0 ）的综合影响，预测运行空间。}MabSelect SuRe LX 树脂在 5 g/L 浓度和RT _C  = 2.8 min 和s下实现了 34.5 g/L/h 生产率和 97.6% 产能利用率的最佳性能 = 87.5%。此外，提出了一种简化的方法来获得最佳的RT _C以获得最大的生产率。结果表明，模型辅助工具可用于确定具有高生产率和产能利用率的 3C-PCC 连续捕获的最佳条件。