Impact of media and antifoam selection on monoclonal antibody production and quality using a high throughput micro-bioreactor system

被引:26
作者
Velugula-Yellela, Sai Rashmika [1 ]
Williams, Abasha [1 ,3 ]
Trunfio, Nicholas [1 ,2 ]
Hsu, Chih-Jung [1 ]
Chavez, Brittany [1 ]
Yoon, Seongkyu [2 ]
Agarabi, Cyrus [1 ]
机构
[1] US FDA, Ctr Drug Evaluat & Res, Off Prod Qual, Off Biotechnol Prod,Div Biotechnol Review & Res 2, Silver Spring, MD 20903 USA
[2] Univ Massachusetts, Dept Chem Engn, Lowell, MA USA
[3] NIAID, VPPL, VRC, NIH, Gaithersburg, MD USA
关键词
antifoam; media scouting; micro-bioreactors; CHO cells; monoclonal antibodies; PLACKETT-BURMAN DESIGN; HAMSTER OVARY CELLS; CHO-CELLS; PROTEIN THERAPEUTICS; CULTURE; AGGREGATION;
D O I
10.1002/btpr.2575
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Monoclonal antibody production in commercial scale cell culture bioprocessing requires a thorough understanding of the engineering process and components used throughout manufacturing. It is important to identify high impact components early on during the lifecycle of a biotechnology-derived product. While cell culture media selection is of obvious importance to the health and productivity of mammalian bioreactor operations, other components such as antifoam selection can also play an important role in bioreactor cell culture. Silicone polymer-based antifoams were known to have negative impacts on cell health, production, and downstream filtration and purification operations. High throughput screening in micro-scale bioreactors provides an efficient strategy to identify initial operating parameters. Here, we utilized a micro-scale parallel bioreactor system to study an IgG1 producing CHO cell line, to screen Dynamis, ProCHO5, PowerCHO2, EX-Cell Advanced, and OptiCHO media, and 204, C, EX-Cell, SE-15, and Y-30 antifoams and their impacts on IgG1 production, cell growth, aggregation, and process control. This study found ProCHO5, EX-Cell Advanced, and PowerCHO2 media supported strong cellular growth profiles, with an IVCD of 25-35 x 10(6) cells-d/mL, while maintaining specific antibody production (Q(p)>2 pg/cell-d) for our model cell line and a monomer percentage above 94%. Antifoams C, EX-Cell, and SE-15 were capable of providing adequate control of foaming while antifoam 204 and Y-30 noticeably stunted cellular growth. This work highlights the utility of high throughput micro bioreactors and the importance of identifying both positive and negative impacts of media and antifoam selection on a model IgG1 producing CHO cell line. (c) 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 34:262-270, 2018
引用
收藏
页码:262 / 270
页数:9
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