Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors
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 ty...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1352098/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xuekun Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T20:28:34Z |
| format | Article |
| id | doaj.art-f622f91f8c874caca261685bcf9c9c2e |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-24T20:28:34Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-f622f91f8c874caca261685bcf9c9c2e2024-03-22T04:47:58ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-03-011210.3389/fbioe.2024.13520981352098Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactorsXuekun Wang0Xuekun Wang1Jin Xu2Jin Xu3Jin Xu4Qingcheng Guo5Qingcheng Guo6Qingcheng Guo7Qingcheng Guo8Zhenhua Li9Zhenhua Li10Zhenhua Li11Jiawei Cao12Jiawei Cao13Jiawei Cao14Rongrong Fu15Rongrong Fu16Mengjiao Xu17Mengjiao Xu18Xiang Zhao19Xiang Zhao20Fugui Wang21Fugui Wang22Xinmeng Zhang23Taimin Dong24Xu Li25Weizhu Qian26Weizhu Qian27Weizhu Qian28Shen Hou29Shen Hou30Shen Hou31Lusha Ji32Lusha Ji33Lusha Ji34Dapeng Zhang35Dapeng Zhang36Dapeng Zhang37Huaizu Guo38Huaizu Guo39Huaizu Guo40Huaizu Guo41State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaTaizhou Mabtech Pharmaceuticals Co., Ltd., Taizhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, ChinaNMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1352098/fullinverted frustoconical shaking bioreactorstirred bioreactorantibody-based biotherapeuticscale-up productionproductivity |
| spellingShingle | 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 Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors Frontiers in Bioengineering and Biotechnology inverted frustoconical shaking bioreactor stirred bioreactor antibody-based biotherapeutic scale-up production productivity |
| title | Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors |
| title_full | Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors |
| title_fullStr | Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors |
| title_full_unstemmed | Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors |
| title_short | Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors |
| title_sort | improving product quality and productivity of an antibody based biotherapeutic using inverted frustoconical shaking bioreactors |
| topic | inverted frustoconical shaking bioreactor stirred bioreactor antibody-based biotherapeutic scale-up production productivity |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1352098/full |
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