Romero Juan J, Jenkins Eleanor W, Birtwistle Marc R, Husson Scott M
Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina, USA.
School of Mathematical and Statistical Sciences, Clemson University, Clemson, South Carolina, USA.
Biotechnol Prog. 2025 Apr 24:e70033. doi: 10.1002/btpr.70033.
Continuous manufacturing platforms and membrane chromatography are process technologies with the potential to reduce production costs and minimize process variability in monoclonal antibody production. This study presents a simulation and optimization framework to perform techno-economic analyses of these strategies. Multi-objective optimization was used to compare batch and continuous multicolumn operating modes and membrane and resin process alternatives, revealing performance differences in productivity and cost of goods attributed to variations in dynamic binding capacity, media geometry, and process residence time. From the set of optimal process configurations, we selected one membrane and one resin platform alternative yielding the highest net present values to undergo sensitivity analyses involving variations in batch cadence and product selling price. For the scenarios considered in this work, membrane continuous platforms showed benefits in the cost of goods and process mass intensity. Their shorter residence time compared to resins positions them as a viable alternative for single-use capture chromatography. Moreover, this low residence time makes membrane platforms more flexible to changes in throughput, an essential feature for integrating capture into fully continuous processes.
连续制造平台和膜色谱是具有降低单克隆抗体制造成本和最小化工艺变异性潜力的工艺技术。本研究提出了一个模拟和优化框架，以对这些策略进行技术经济分析。多目标优化用于比较分批和连续多柱操作模式以及膜和树脂工艺替代方案，揭示了由于动态结合容量、介质几何形状和工艺停留时间的变化而导致的生产率和商品成本的性能差异。从一组最优工艺配置中，我们选择了一个膜平台和一个树脂平台替代方案，它们具有最高的净现值，以进行涉及分批节奏和产品售价变化的敏感性分析。对于本工作中考虑的场景，膜连续平台在商品成本和工艺质量强度方面显示出优势。与树脂相比，它们较短的停留时间使其成为一次性捕获色谱的可行替代方案。此外，这种低停留时间使膜平台对产量变化更具灵活性，这是将捕获集成到完全连续工艺中的一个基本特征。
