Manufacturing Process Optimization, Catalent Biologics, Madison, Wisconsin, USA.
Separation and Purification Sciences Division, 3M Company, Saint Paul, Minnesota, USA.
Biotechnol Prog. 2022 Mar;38(2):e3227. doi: 10.1002/btpr.3227. Epub 2021 Dec 8.
Recent advancements in cell culture engineering have allowed drug manufacturers to achieve higher productivity by driving higher product titers through cell line engineering and high-cell densities. However, these advancements have shifted the burden to clarification and downstream processing where the difficulties now revolve around removing higher levels of process- and product-related impurities. As a result, a lot of research efforts have turned to developing new approaches and technologies or process optimization to still deliver high quality biological products while controlling cost of goods. Here, we explored the impact of a novel single use technology employing chromatographic principle-based clarification for a process-intensified cell line technology. In this study, a 16% economic benefit ($/g) was observed using a single-use chromatographic clarification compared to traditional single-use clarification technology by improving the overall product cost through decreased operational complexity, higher loading capacity, increased product recovery, and higher impurity clearance. In the end, the described novel chromatographic approach significantly simplified and enhanced the cell culture fluid harvest unit operation by combining the reduction of insoluble and key soluble contaminants of the harvest fluid into a single stage.
近年来，细胞培养工程的进步使药物制造商能够通过细胞系工程和高细胞密度来提高产品滴度，从而实现更高的生产力。然而，这些进步将负担转移到了澄清和下游处理上，现在的困难围绕着去除更高水平的工艺相关和产品相关杂质。因此，大量的研究工作转向开发新的方法和技术或工艺优化，以在控制产品成本的同时仍能提供高质量的生物制品。在这里，我们探讨了一种新颖的一次性使用技术对工艺强化细胞系技术的基于色谱原理的澄清的影响。在这项研究中，与传统的一次性使用澄清技术相比，使用一次性使用色谱澄清可提高 16%的经济效益（$/g），这是通过降低操作复杂性、提高载量、提高产品回收率和提高杂质清除率来降低整体产品成本实现的。最后，所描述的新颖色谱方法通过将收获液中不溶性和关键可溶性污染物的减少合并到一个阶段，显著简化和增强了细胞培养液收获单元操作。
