Improving productivity and decreasing costs for biotherapeutic agents has been a focal driving force in the manufacturing of biologics. Advances in upstream processes have been continuously outpacing the ability for downstream operations to purify biologics, especially monoclonal antibodies. Continuous chromatography has several benefits for biologic purification including automated control, decreased labor, improved productivity, and more consistent product attributes. The goal of this study was to improve productivity and decrease costs associated with batch-mode and continuous purification processes. Productivities using cellulose nanofibers with a protein A ligand offer greater than 30-fold higher productivities than their resin-based equivalents using periodic countercurrent technology with multiple column chromatography. The smaller columns needed for convective mass transfer, faster processing times, and decreased costs allow for a more efficient mAb capture step. Additionally, high throughput purification (grams of mAbs/day) can be achieved from the scale-down model developed using periodic countercurrent technology. These advancements will help drive the evolution of downstream operations to manage the higher workloads due to increased upstream titers in a cost-effective manner.

提高生物治疗药物的生产率和降低成本一直是生物制剂制造的主要驱动力。上游工艺的进步不断超过下游纯化生物制剂（尤其是单克隆抗体）的能力。连续色谱法对于生物纯化有多种好处，包括自动化控制、减少劳动力、提高生产率和更一致的产品属性。本研究的目标是提高生产率并降低与批量模式和连续纯化过程相关的成本。使用具有蛋白 A 配体的纤维素纳米纤维的生产率比使用周期​​性逆流技术和多柱色谱的树脂基同类产品的生产率高出 30 倍以上。对流传质所需的色谱柱更小、处理时间更快并且成本更低，从而实现更高效的 mAb 捕获步骤。此外，可以通过使用周期性逆流技术开发的缩小模型来实现高通量纯化（单克隆抗体克数/天）。这些进步将有助于推动下游运营的发展，以经济高效的方式管理因上游滴度增加而产生的更高工作负载。