Frontiers in Bioengineering and Biotechnology (Mar 2024)

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

  • Xuekun Wang,
  • Xuekun Wang,
  • Jin Xu,
  • Jin Xu,
  • Jin Xu,
  • Qingcheng Guo,
  • Qingcheng Guo,
  • Qingcheng Guo,
  • Qingcheng Guo,
  • Zhenhua Li,
  • Zhenhua Li,
  • Zhenhua Li,
  • Jiawei Cao,
  • Jiawei Cao,
  • Jiawei Cao,
  • Rongrong Fu,
  • Rongrong Fu,
  • Mengjiao Xu,
  • Mengjiao Xu,
  • Xiang Zhao,
  • Xiang Zhao,
  • Fugui Wang,
  • Fugui Wang,
  • Xinmeng Zhang,
  • Taimin Dong,
  • Xu Li,
  • Weizhu Qian,
  • Weizhu Qian,
  • Weizhu Qian,
  • Shen Hou,
  • Shen Hou,
  • Shen Hou,
  • Lusha Ji,
  • Lusha Ji,
  • Lusha Ji,
  • Dapeng Zhang,
  • Dapeng Zhang,
  • Dapeng Zhang,
  • Huaizu Guo,
  • Huaizu Guo,
  • Huaizu Guo,
  • Huaizu Guo

DOI
https://doi.org/10.3389/fbioe.2024.1352098
Journal volume & issue
Vol. 12

Abstract

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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.

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