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中国生物工程杂志

China Biotechnology
China Biotechnology  2019, Vol. 39 Issue (3): 105-110    DOI: 10.13523/j.cb.20190313
    
The Research Progress of Perfusion Mammalian Cell Culture
Shuang SU1,Yong-jie JIN2,Rui-jing HUANG2,Jian LI2,**(),Han-mei XU1,**()
1 China Pharmaceutical University, Nanjing 211100, China
2 Tasly Biomedical Co., Ltd., Shanghai 201203, China
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Abstract  

In the current environment of biopharmaceuticals, cost pressures, rapidly fluctuating market demands and growing competition among biosimilars, existing bio-manufacturing technologies are challenged, and so that biotechnology companies are increasingly driven to develop innovative solutions for highly flexible and cost-effective manufacturing. As one of the important processes in mammalian cell culture, perfusion culture has two advantages. Firstly, it can provide a stable environment favorable to cells by continuously removing by-products and adding nutrients, so that it can solve the problems of unstable protein amount or low expression level. Also, it can optimize capacity utilization and increase production efficiency by increasing volumetric productivity. This paper systematically reviewed the progress of perfusion culture for mammalian cell culture,and it provides reference for further development and application.



Key wordsPerfusion      culture      Mammalian      cells      Culture      process      Continuous      process     
Received: 03 September 2018      Published: 12 April 2019
ZTFLH:  R392  
Corresponding Authors: Jian LI,Han-mei XU     E-mail: lijian16@tasly.com;1037714870@qq.com
Cite this article:

Shuang SU,Yong-jie JIN,Rui-jing HUANG,Jian LI,Han-mei XU. The Research Progress of Perfusion Mammalian Cell Culture. China Biotechnology, 2019, 39(3): 105-110.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20190313     OR     https://manu60.magtech.com.cn/biotech/Y2019/V39/I3/105

[1]   Gaughan C L . The present state of the art in expression, production and characterization of monoclonal antibodies. Molecular Diversity, 2016,20(1):255-270.
doi: 10.1007/s11030-015-9625-z pmid: 26299798
[2]   Sommeregger W, Mayrhofer P, Steinfellner W , et al. Proteomic differences in recombinant CHO cells producing two similar antibody fragments. Biotechnology & Bioengineering, 2016,113(9):1902-1912.
doi: 10.1002/bit.25957 pmid: 26913574
[3]   Karst D J, Scibona E, Serra E , et al. Modulation and modeling of monoclonal antibody N-linked glycosylation in mammalian cell perfusion reactors. Biotechnology & Bioengineering, 2017,114(9):1978-1990.
doi: 10.1002/bit.26315 pmid: 28409838
[4]   Karst D J, Steinebach F, Morbidelli M . Continuous integrated manufacturing of therapeutic proteins. Current Opinion in Biotechnology, 2017,53:76-84.
doi: 10.1016/j.copbio.2017.12.015
[5]   Kleinebudde P, Khinast J, Rantanen J . Regulatory and quality considerations for continuous manufacturing//Continuous manufacturing of pharmaceuticals. Hoboken: John Wiley & Sons, Ltd, 2017: 107-125.
[6]   Tapia F, Vázquez-Ramírez D, Genzel Y , et al. Bioreactors for high cell density and continuous multi-stage cultivations: Options for process intensification in cell culture-based viral vaccine production. Applied Microbiology & Biotechnology, 2016,100(5):2121-2132.
[7]   Ahn W S, Jeon J J, Jeong Y R , et al. Effect of culture temperature on erythropoietin production and glycosylation in a perfusion culture of recombinant CHO cells. Biotechnology & Bioengineering, 2010,101(6):1234-1244.
doi: 10.1002/bit.22006 pmid: 18980186
[8]   Pollock J, Ho S V, Farid S S . Fed-batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty. Biotechnology & Bioengineering, 2013,110(1):206-219.
doi: 10.1002/bit.24608 pmid: 22806692
[9]   肖成祖, 陈昭烈, 黄子才 , 等. 动物细胞微载体灌流培养技术的研究和应用. 医学研究杂志, 2000,29(11):16-17.
[9]   Xiao C Z, Chen Z L, Huang Z C , et al. Research and application of animal cell microcarrier perfusion culture technology. Journal of Medical Research, 2000,29(11):16-17.
[10]   米力, 李玲, 冯强 , 等. 连续灌流培养杂交瘤细胞生产单克隆抗体. 生物工程学报, 2002,18(3):360-364.
doi: 10.3321/j.issn:1000-3061.2002.03.023
[10]   Mi L, Li L, Feng Q , et al. Production of monoclonal antibodies by continuous perfusion culture of hybridoma cells. Chinese Journal of Biotechnology, 2002,18(3):360-364.
doi: 10.3321/j.issn:1000-3061.2002.03.023
[11]   米力, 陈志南 . 动物细胞大规模培养生产蛋白的工艺选择. 中国生物工程杂志, 2003,23(7):1-6.
[11]   Mi L, Chen Z N . Process selection for large-scale culture of animal cells to produce protein. China Biotechnology, 2003,23(7):1-6.
[12]   赵子淇, 褚淑贞, 吴洁 . 基于DCF模型的创新药品估值研究——以普佑克为例. 现代商贸工业, 2018(13):71-72.
doi: 10.19311/j.cnki.1672-3198.2018.13.030
[12]   Zhao Z Q, Zhu S Z, Wu J . Research on the evaluation of innovative drugs based on DCF model——Taking puyouke as an example. Modern Business Trade Industry, 2018,13:71-72.
doi: 10.19311/j.cnki.1672-3198.2018.13.030
[13]   Warikoo V, Godawat R, Brower K , et al. Integrated continuous production of recombinant therapeutic proteins. Biotechnology & Bioengineering, 2012,109(12):3018-3029.
doi: 10.1002/bit.24584 pmid: 22729761
[14]   李尤, 周航, 李锦才 , 等. 哺乳动物细胞灌流培养技术的开发与应用. 中国医药生物技术, 2015,10(3):267-270.
[14]   Li Y, Zhou H, Li J C , et al. Development and application of mammalian cell perfusion culture technology. Chinese Medicinal Biotechnology, 2015,10(3):267-270.
[15]   Zhang Y, Stobbe P, Silvander C O , et al. Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor. Journal of Biotechnology, 2015,213:28-41.
doi: 10.1016/j.jbiotec.2015.07.006 pmid: 26211737
[16]   Bosco B, Paillet C, Amadeo I , et al. Alternating flow filtration as an alternative to internal spin filter based perfusion process: Impact on productivity and product quality. Biotechnology Progress, 2017,33(4):1010-1014.
doi: 10.1002/btpr.2487 pmid: 28445603
[17]   Clincke M, Mölleryd C, Zhang Y , et al. Study of a recombinant CHO cell line producing a monoclonal antibody by ATF or TFF external filter perfusion in a WAVE Bioreactor TM . Bmc Proceedings, 2011,5(S8):105-107.
doi: 10.1186/1753-6561-5-S8-P105 pmid: 22373105
[18]   Kwon T, Prentice H, Oliveira J D , et al. Microfluidic cell retention device for perfusion of mammalian suspension culture. Scientific Reports, 2017,7(1):6703-6713.
doi: 10.1038/s41598-017-06949-8 pmid: 5532224
[19]   Karst D J, Serra E, Villiger T K , et al. Characterization and comparison of ATF and TFF in stirred bioreactors for continuous mammalian cell culture processes. Biochemical Engineering Journal, 2016,110:17-26.
doi: 10.1016/j.bej.2016.02.003
[20]   Steinebach F, Angarita M, Karst D J , et al. Model based adaptive control of a continuous capture process for monoclonal antibodies production. Journal of Chromatography A, 2016,1444:50-56.
doi: 10.1016/j.chroma.2016.03.014 pmid: 27046002
[21]   Angelo J, Pagano J, Müller-Späth T , et al. Scale-up of twin-column periodic counter-current chromatography for MAb purification. Bioprocess International, 2018,16(4):1-6.
[22]   Steinebach F, Ulmer N, Wolf M , et al. Design and operation of a continuous integrated monoclonal antibody production process. Biotechnology Progress, 2017,33(5):1303-1313.
doi: 10.1002/btpr.2522 pmid: 28691347
[23]   Tao Y, Shih J, Sinacore M , et al. Development and implementation of a perfusion-based high cell density cell banking process. Biotechnology Progress, 2011,27(3):824-829.
doi: 10.1002/btpr.v27.3
[24]   Wright B, Bruninghaus M, Vrabel M , et al. A novel seed-train process: Using high-density cell banking, a disposable bioreactor, and perfusion technologies. Bioprocess International, 2015,13(3):16-25.
[25]   Yang W C, Minkler D F, Kshirsagar R , et al. Concentrated fed-batch cell culture increases manufacturing capacity without additional volumetric capacity. Journal of Biotechnology, 2016,217:1-11.
doi: 10.1016/j.jbiotec.2015.10.009
[26]   Hiller G W, Ovalle A M, Gagnon M P , et al. Cell-controlled hybrid perfusion fed-batch CHO cell process provides significant productivity improvement over conventional fed-batch cultures. Biotechnology & Bioengineering, 2017,114(7):1438-1447.
[27]   Yang W C, Jiuyi L, Chris K , et al. Perfusion seed cultures improve biopharmaceutical fed-batch production capacity and product quality. Biotechnology Progress, 2014,30(3):616-625.
doi: 10.1002/btpr.1884
[28]   Rodriguez J, Spearman M, Tharmalingam T , et al. High productivity of human recombinant beta-interferon from a low-temperature perfusion culture. Journal of Biotechnology, 2010,150(4):509-518.
doi: 10.1016/j.jbiotec.2010.09.959 pmid: 20933553
[29]   Yao T, Asayama Y . Animal-cell culture media: History, characteristics, and current issues. Reproductive Medicine & Biology, 2017,16(2):99-117.
doi: 10.1002/rmb2.12024
[30]   Lin H, Leighty R W, Godfrey S , et al. Principles and approach to developing mammalian cell culture media for high cell density perfusion process leveraging established fed-batch media. Biotechnol Progress, 2017,33(4):891-902.
doi: 10.1002/btpr.2472 pmid: 28371394
[31]   Bareither R, Bargh N, Oakeshott R , et al. Automated disposable small scale reactor for high throughput bioprocess development: A proof of concept study. Biotechnology & Bioengineering, 2013,110(12):3126-3138.
doi: 10.1002/bit.24978 pmid: 23775295
[32]   Gomez N, Ambhaikar M, Zhang L , et al. Analysis of tubespins as a suitable scale-down model of bioreactors for high cell density CHO cell culture. Biotechnology Progress, 2016,33(2):490-523.
doi: 10.1002/btpr.2418 pmid: 27977914
[33]   Bielser J M, Wolf M, Souquet J , et al. Perfusion mammalian cell culture for recombinant protein manufacturing-A critical review. Biotechnology Advances, 2018,36(4):1328-1340.
doi: 10.1016/j.biotechadv.2018.04.011 pmid: 29738813
[34]   Allison G, Cain Y T, Cooney C L , et al. Regulatory and quality considerations for continuous manufacturing. Journal of Pharmaceutical Sciences, 2015,104(3):803-812.
doi: 10.1002/jps.24324 pmid: 25830179
[35]   Xu S, Jiang R, Chen Y , et al. Impact of Pluronic ® F68 on hollow fiber filter-based perfusion culture performance . Bioprocess & Biosystems Engineering, 2017,40(9):1-10.
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