Technical Development, Biogen, Research Triangle Park, North Carolina, USA.
Biotechnol Bioeng. 2021 Sep;118(9):3359-3366. doi: 10.1002/bit.27733. Epub 2021 Mar 25.
Recent interest in continuous manufacturing of biologics has driven the development and evaluation of multicolumn chromatography systems to drive down resin costs by increasing productivity and maximizing resin utilization, especially for the expensive protein A capture step. Single-pass tangential flow filtration can be used to reduce the volume of perfusion harvest, enabling a further increase in the productivity of the capture step by up to fivefold. However, there are expected to be practical limits for the productivity of the capture step, which must be determined based on the manufacturing batch size, duration, and frequency, especially as it relates to efficient utilization of the column lifetime. For short fed-batch manufacturing campaigns, intensified capture processes may result in up to 82% lower resin consumption, while avoiding the long-term storage of used resin. For perfusion processes and longer fed-batch campaigns, it may be more efficient to operate at a lower productivity that enables the column lifetime to be routinely achieved and achieves the desired resin and buffer savings without introducing unnecessary process risk or complexity. An intensified batch capture process, "super-batch," will be compared as an alternative to multicolumn chromatography processes to achieve high productivity and resin utilization with a potentially simpler process.
最近人们对生物制品连续制造的兴趣推动了多柱层析系统的开发和评估，以通过提高生产力和最大化树脂利用率来降低树脂成本，特别是对于昂贵的蛋白 A 捕获步骤。单次通过切向流过滤可用于减少灌注收获的体积，从而使捕获步骤的生产力提高多达五倍。然而，捕获步骤的生产力预计会有实际限制，必须根据制造批次大小、持续时间和频率来确定，特别是与柱寿命的有效利用有关。对于短期补料分批制造活动，强化捕获过程可能导致树脂消耗降低高达 82%，同时避免使用过的树脂的长期储存。对于灌注过程和更长的补料分批活动，以较低的生产力运行可能更有效，这可以使柱寿命常规实现，并在不引入不必要的工艺风险或复杂性的情况下实现所需的树脂和缓冲液节省。强化批处理捕获过程“超级批处理”将作为多柱层析过程的替代方案进行比较，以实现高生产力和树脂利用率，同时具有潜在更简单的工艺。
