Optimization of the Process of Chinese Hamster Ovary (CHO) Cell Fed-Batch Culture to Stabilize Monoclonal Antibody Production and Overall Quality: Effect of pH Control Strategies

Author:

Liang Kexue1,Luo Hongzhen12ORCID,Li Qi1

Affiliation:

1. Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China

2. School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China

Abstract

Monoclonal antibodies (mAbs) used in biomedical research and therapeutic applications are primarily produced by Chinese hamster ovary (CHO) cells via fed-batch culture. The growing need for elevated quantities of biologics mandates the continual optimization of the mAb production process. The development of an effective process control method is indispensable for the production of specified mAbs by CHO cells. In this study, the effects of the pH control strategy on CHO cell fed-batch culture to produce an antibody (EA5) were first investigated in a 3 L bioreactor. The results indicate that controlling the culture pH at 7.2 during the fed-batch stage could produce a higher EA5 titer of 6.1 g/L with a lower Man5 ratio of 2.2% by day 14. Based on this, an optimized CHO cell fed-batch culture was conducted in a 15 L bioreactor to verify its effectiveness and stability. In this case, on day 14, an EA5 titer of 6.5 g/L was achieved with productivity of 0.46 g/L/day, which was 1.07-fold higher compared to that of the culture in the 3 L bioreactor. Furthermore, regarding the product quality, a monomer abundance of 96.0%, a main peak of 55.0%, and a Man5 proportion of 2.4% were maintained in the 15 L bioreactor. In addition, different cell clarification processes were evaluated using the CHO cell culture broth from the 3 L and 15 L bioreactors to further improve productivity and economic performance. Overall, this study provides some directions for process intensification and improving the quality of mAbs produced by CHO cells in the biopharmaceutical industry.

Publisher

MDPI AG

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