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Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors

Authors :
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
Source :
Frontiers in Bioengineering and Biotechnology, Vol 12 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

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.

Details

Language :
English
ISSN :
22964185
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Bioengineering and Biotechnology
Publication Type :
Academic Journal
Accession number :
edsdoj.f622f91f8c874caca261685bcf9c9c2e
Document Type :
article
Full Text :
https://doi.org/10.3389/fbioe.2024.1352098