Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors,Frontiers in Bioengineering and Biotechnology

当前位置： X-MOL 学术 › Front. Bioeng. Biotech. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors
Frontiers in Bioengineering and Biotechnology ( IF 5.7 ) Pub Date : 2024-03-22 , DOI: 10.3389/fbioe.2024.1352098
Xuekun Wang , Jin Xu , Qingcheng Guo , Zhenhua Li , Jiawei Cao , Rongrong Fu , Mengjiao Xu , Xiang Zhao , Fugui Wang , Xinmeng Zhang , Taimin Dong , Xu Li , Weizhu Qian , Shen Hou , Lusha Ji , Dapeng Zhang , Huaizu Guo

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%–22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

更新日期：2024-03-22

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文

全部期刊列表>>