Improved Titer in Late-Stage Mammalian Cell Culture Manufacturing by Re-Cloning

Improving productivity to reduce the cost of biologics manufacturing and ensure that therapeutics can reach more patients remains a major challenge faced by the biopharmaceutical industry. Chinese hamster ovary (CHO) cell lines are commonly prepared for biomanufacturing by single cell cloning post-t...

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Published inBioengineering (Basel) Vol. 9; no. 4; p. 173
Main Authors He, Qin, Rehmann, Matthew S, Tian, Jun, Xu, Jianlin, Sabino, Luzmary, Vandermark, Erik, Basson, Ziev, Po, Iris, Bierilo, Kathleen, Tremml, Gabi, Rizzi, Giovanni, Langsdorf, Erik F, Qian, Nan-Xin, Borys, Michael C, Khetan, Anurag, Li, Zheng-Jian
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 15.04.2022
MDPI
Subjects
Bioengineering
Biological products
biologics manufacturing
Biopharmaceuticals
Bioreactors
Cell culture
cell culture platform
Cell lines
Chinese hamster ovary cells
Cloning
Dihydrofolate reductase
DNA methylation
Gene expression
Glucose
Laboratories
Manufacturing
Monoclonal antibodies
Product quality
Productivity
Proprietary
Quality management
re-cloning
titer
Transfection
United States > US
titer
cell culture platform
biologics manufacturing
re-cloning
Chinese hamster ovary cells
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Summary:Improving productivity to reduce the cost of biologics manufacturing and ensure that therapeutics can reach more patients remains a major challenge faced by the biopharmaceutical industry. Chinese hamster ovary (CHO) cell lines are commonly prepared for biomanufacturing by single cell cloning post-transfection and recovery, followed by lead clone screening, generation of a research cell bank (RCB), cell culture process development, and manufacturing of a master cell bank (MCB) to be used in early phase clinical manufacturing. In this study, it was found that an additional round of cloning and clone selection from an established monoclonal RCB or MCB (i.e., re-cloning) significantly improved titer for multiple late phase monoclonal antibody upstream processes. Quality attributes remained comparable between the processes using the parental clones and the re-clones. For two CHO cells expressing different antibodies, the re-clone performance was successfully scaled up at 500-L or at 2000-L bioreactor scales, demonstrating for the first time that the re-clone is suitable for late phase and commercial manufacturing processes for improvement of titer while maintaining comparable product quality to the early phase process.
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These authors contributed equally to this work.
Current Address: Novavax, Gaithersburg, MD 20878, USA.
Current Address: WuXi Biologics, Wuxi, 200131 China.
Current Address: Horizon Therapeutics, Rockville, MD 20850, USA.
Current Address: Helaina, New York, NY 10002, USA.
ISSN:2306-5354
2306-5354
DOI:10.3390/bioengineering9040173