期刊
VACCINE
卷 37, 期 43, 页码 6380-6389出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2019.09.013
关键词
Scale-down model; FMD vaccine; Cell culture; CFD simulation; QbD
资金
- National Natural Science Foundation of China [31570034]
- National First-class Discipline Program of Light Industry Technology and Engineering [LITE2018-24]
- Opening Project of the Key Laboratory of Industrial Biotechnology, Ministry of Education [KLIB-KF201802]
- Collaborative Innovation Center of Jiangsu Modern Industrial Fermentation
- 111 Project [111-2-06]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Achievements Transformation Project of Gansu Province [17ZD4CA010]
- Research Innovation Program for College Graduates of Jiangsu Province [KYLX16_0807]
The anticipated increasing demand for inactivated foot-and-mouth (FMD) disease vaccine calls for its larger production capacity, while development of a large-scale process typically requires high running cost and has very limited experimental throughput at manufacturing scale. Thus, an economic scale-down model of representing a large-scale process becomes necessary and essential. In this study, we used a systematic approach to establish a scale-down model representing a 4000-L culture process for FMD vaccine production by suspension BHK-21 cells. In detail, we firstly compared hydrodynamic properties of three bioreactors (14-L, 800-L and 4000-L) under three different conditions (equivalent mixing time, equivalent shear stress and equivalent volumetric power). We figured out equivalent volumetric power (P/V) potentially as an appropriate scale-down strategy, since it resulted in comparable calculated hydrodynamic parameters among three bioreactors. Next, we used computational fluid dynamics (CFD) simulation to provide more details about hydrodynamic environments inside the bioreactors, which supports the reliability of this scale-down strategy. Finally, we compared cell growth, metabolites, vaccine productivity and product quality attributes during FMD vaccine production by BHK-21 cells and observed very close performances among three bioreactors, which once again demonstrates the robustness of this scale-down model. This scale-down strategy can be applied to study variations and critical quality attributes (CQAs) in the resultant production process based on quality by design (QbD) principles, aiming at further more efficient optimization of vaccine production. (C) 2019 Elsevier Ltd. All rights reserved.
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