连续流层析在单抗亲和层析中的应用

The Application of Continuous Purification in Monoclonal Antibody Affinity Chromatography

亲和层析作为单克隆抗体分离纯化的关键步骤,其工艺设计对生产效率和成本具有重要影响。对比批次层析和连续流层析两种工艺模式,以期提高亲和层析填料的使用效率,降低生产成本。采用GE公司KTA PCC设备,对比考察两款亲和层析介质在批次层析及连续流层析两种生产模式下产品的关键质量属性,如聚合物、降解物、电荷异构体、工艺杂质残留等,以及关键工艺属性,如回收率、生产效率、填料量等。连续流层析工艺稳定,纯化回收率与批次层析接近。此外,尽管多根层析柱串联上样,洗脱中间体产品关键质量属性无明显差异,但生产效率明显提高,填料用量显著减少。与批次层析工艺相比,连续流层析可显著减少亲和填料的用量,减少缓冲液的消耗,显著提高生产效率,降低生产成本。

Affinity chromatography is a critical step in the purification process of monoclonal antibodies,and its process design has an important impact on production efficiency and cost. In order to increase the utilization efficiency of the affinity chromatography resins and reduce the production cost,we compared batch process mode with continuous purification mode. We compared the critical quality attributes of products,such as polymers,degradation products,charge variants and process impurities,as well as key mass attributes such as recovery,production efficiency and resin usage of the two purification mode using GE KTA PCC and two affinity chromatography resins. The continuous chromatography process was stable,and the purification recovery was close to the batch mode.In addition,although multiple chromatographic columns were loaded in series,there was no significant difference in the critical quality attributes of the elution intermediates for each run. However,the production efficiency was significantly improved and the usage of the chromatography resin was significantly reduced. Compared with the batch purification process,continuous purification can significantly reduce the usage of the chromatography resin,reduce buffer consumption,significantly increase production efficiency,and reduce production cost.