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Optimization of the cell specific perfusion rate in high cell density perfusion process
KTH, School of Biotechnology (BIO), Industrial Biotechnology. (Animal Cell Technology)ORCID iD: 0000-0002-0841-8845
KTH, School of Biotechnology (BIO), Industrial Biotechnology. (Animal Cell Technology)
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(English)Manuscript (preprint) (Other academic)
National Category
Bioprocess Technology
Identifiers
URN: urn:nbn:se:kth:diva-207741OAI: oai:DiVA.org:kth-207741DiVA, id: diva2:1097864
Note

QC 20170523

Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-05-23Bibliographically approved
In thesis
1. High cell density perfusion process development for antibody producing Chinese Hamster Ovary cells
Open this publication in new window or tab >>High cell density perfusion process development for antibody producing Chinese Hamster Ovary cells
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Perfusion operation mode is currently under fast expansion in mammalian cell based manufacturing of biopharmaceuticals, not only for labile drug protein but also for stable proteins such as monoclonal antibodies (mAbs). Perfusion mode can advantageously offer a stable cell environment, long-term production with high productivity and consistent product quality. Intensified high cell density culture (HCDC) is certainly one of the most attractive features of a perfusion process due to the high volumetric productivity in a small footprint that it can provide. Advancements in single-use technology have alleviated the intrinsic complexity of perfusion processes while the maturing in cell retention devices has improved process robustness. The knowledge for perfusion process has been gradually built and the “continuous” concept is getting more and more acceptance in the field.

This thesis presents the development of robust perfusion process at very high cell densities in various culture systems. Four HCDC perfusion systems were developed with industrial collaborators with three different mAb producing Chinese Hamster Ovary (CHO) cell lines: 1-2) WAVE Bioreactor™ Cellbag prototype equipped with cell separation by hollow fiber filter utilizing Alternating Tangential Flow (ATF) and Tangential Flow Filtration (TFF) techniques; 3) Fiber matrix based CellTank™ prototype; 4) Glass stirred tank bioreactor equipped with ATF. In all the systems, extremely high viable cell densities above 130 million viable cells per milliliter (MVC/mL) up to 214 MVC/mL were achieved. Steady states were maintained and studied at 20-30 MVC/mL and 100-130 MVC/mL for process development. Perfusion rate selection based on cell specific perfusion rate (CSPR) was systematically investigated and exometabolome study was performed to explore the metabolic footprint of HCDC perfusion process.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. p. 79
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:14
Keywords
WAVE Bioreactor, Cellbag, ATF, TFF, hollow fiber, CSPR, CellTank, SUB, single-use-bioreactor, disposable, perfusion rate
National Category
Bioprocess Technology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-207600 (URN)978-91-7729-450-4 (ISBN)
Public defence
2017-06-14, FB54, Albanova, plan_5, Stockholm, 14:00 (English)
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Note

QC 20170523

Available from: 2017-05-23 Created: 2017-05-22 Last updated: 2017-05-29Bibliographically approved

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CiteExportLink to record
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