Biotechnology and Bioprocess Engineering 2021; 26(6): 993-1001  
Commercial-scale Economic Comparison of Different Batch Modes for Upstream and Downstream Processing of Monoclonal Antibody
Hyun-Myoung Cha, Jeong-Min Hwang, Jung-Heum Yeon, Jin-Hyuk Lim, Hye-Jin Han, and Dong-Il Kim
Hyun-Myoung Cha, Jeong-Min Hwang, Jung-Heum Yeon, Jin-Hyuk Lim, Hye-Jin Han, Dong-Il Kim*
Department of Biological Engineering, Inha University, Incheon 22212, Korea
Tel: +82-32-860-7515; Fax: +82-32-872-4046
These authors contributed equally to this article.
Received: December 17, 2020; Revised: February 18, 2021; Accepted: March 14, 2021; Published online: December 31, 2021.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chinese hamster ovary (CHO) cell cultures are widely used due to their high productivity, industrial track record, safety record, and correct post-translational modifications. Fed-batch and perfusion modes have been mostly adopted as traditional commercial manufacturing process using CHO cells for the production of biopharmaceuticals. Thus, we compared fed-batch and perfusion culture processes for the commercial-scale production of monoclonal antibody. Main production process was performed after confirming the comparable culture performance in seed train of different operation modes, and then perfusion cultures showed 1.6-fold higher peak viable cell density (VCD) with a longer culture duration than that of fed-batch cultures. Also, as the result of main batches, total product amount increased over 450% in perfusion cultures. Importantly, perfusion process allowed to improve the higher purification yield while maintaining acceptable product quality, because the level of process impurity could be reduced by using retention device. When economic comparison of fed-batch versus perfusion processes was carried out under the equal scale of upstream and downstream, perfusion mode was more a cost-effective bioprocess that could reduce the cost of goods. In conclusion, although comparison data of triplicate commercial batches are of course specific case for a given antibody production, this study verified the possibility of using perfusion mode as an efficient system for commercial producing the desired antibody and is a meaningful report in the biopharmaceutical industry.
Keywords: ATF system, Chinese hamster ovary cell, fed-batch culture, monoclonal antibody, perfusion culture

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