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Perfusion Control for High Cell Density Cultivation and Viral Vaccine Production

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Animal Cell Biotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2095))

Abstract

The global demand for complex biopharmaceuticals like recombinant proteins, vaccines, or viral vectors is steadily rising. To further improve process productivity and to reduce production costs, process intensification can contribute significantly. The design and optimization of perfusion processes toward very high cell densities require careful selection of strategies for optimal perfusion rate control. In this chapter, various options are discussed to guarantee high cell-specific virus yields and to achieve virus concentrations up to 1010 virions/mL. This includes reactor volume exchange regimes and perfusion rate control based on process variables such as cell concentration and metabolite or by-product concentration. Strategies to achieve high cell densities by perfusion rate control and their experimental implementation are described in detail for pseudo-perfusion or small-scale perfusion bioreactor systems. Suspension cell lines such as MDCK, BHK-21, EB66®, and AGE1.CR.pIX® are used to exemplify production of influenza, yellow fever, Zika, and modified vaccinia Ankara virus.

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Acknowledgments

We would like to thank our former colleague Daniel V. Ramirez for experimental data on the lactate-based perfusion rate control and for the provision of the ATF bioreactor illustration. Furthermore, we would like to express our gratitude to our collaboration partners for the allowance to work with the cell lines (ProBioGen AG, AGE1.CRpIX; Valneva, EB66®; IDT, BHK-21; East China University of Science and Technology, MDCK). Additionally, we thank Hamilton Bonaduz AG for providing the analog output box and Eppendorf for the implementation to the DasGip control system. Our gratitude also goes to Sartorius AG for providing the BioPAT Trace system.

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Author notes

  1. Alexander Nikolay and Thomas Bissinger contributed equally to this work.

Authors and Affiliations

  1. Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

    Alexander Nikolay, Thomas Bissinger, Gwendal Gränicher, Yvonne Genzel & Udo Reichl

  2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China

    Yixiao Wu

  3. Bioprocess Engineering, Otto von Guericke University Magdeburg, Magdeburg, Germany

    Udo Reichl

Authors
  1. Alexander Nikolay
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  2. Thomas Bissinger
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  3. Gwendal Gränicher
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  4. Yixiao Wu
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  5. Yvonne Genzel
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  6. Udo Reichl
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Corresponding author

Correspondence to Alexander Nikolay .

Editor information

Editors and Affiliations

  1. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology (TUHH), Hamburg, Germany

    Ralf Pörtner

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Nikolay, A., Bissinger, T., Gränicher, G., Wu, Y., Genzel, Y., Reichl, U. (2020). Perfusion Control for High Cell Density Cultivation and Viral Vaccine Production. In: Pörtner, R. (eds) Animal Cell Biotechnology. Methods in Molecular Biology, vol 2095. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0191-4_9

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  • DOI: https://doi.org/10.1007/978-1-0716-0191-4_9

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0190-7

  • Online ISBN: 978-1-0716-0191-4

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