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Continuous Manufacturing of Recombinant Therapeutic Proteins: Upstream and Downstream Technologies

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New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 165))

Abstract

Continuous biomanufacturing of recombinant therapeutic proteins offers several potential advantages over conventional batch processing, including reduced cost of goods, more flexible and responsive manufacturing facilities, and improved and consistent product quality. Although continuous approaches to various upstream and downstream unit operations have been considered and studied for decades, in recent years interest and application have accelerated. Researchers have achieved increasingly higher levels of process intensification, and have also begun to integrate different continuous unit operations into larger, holistically continuous processes. This review first discusses approaches for continuous cell culture, with a focus on perfusion-enabling cell separation technologies including gravitational, centrifugal, and acoustic settling, as well as filtration-based techniques. We follow with a review of various continuous downstream unit operations, covering categories such as clarification, chromatography, formulation, and viral inactivation and filtration. The review ends by summarizing case studies of integrated and continuous processing as reported in the literature.

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  1. Bioprocess Development, Sanofi, Framingham, MA, 01701, USA

    Rohan Patil & Jason Walther

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  1. Rohan Patil
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Correspondence to Jason Walther .

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  1. Sutro Biopharma Inc., San Francisco, CA, USA

    Bob Kiss

  2. Lonza, Basel, Switzerland

    Uwe Gottschalk

  3. Solothurn Manufacturing Facility, Biogen International GmbH, Luterbach, Switzerland

    Michael Pohlscheidt

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Patil, R., Walther, J. (2017). Continuous Manufacturing of Recombinant Therapeutic Proteins: Upstream and Downstream Technologies. In: Kiss, B., Gottschalk, U., Pohlscheidt, M. (eds) New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins. Advances in Biochemical Engineering/Biotechnology, vol 165. Springer, Cham. https://doi.org/10.1007/10_2016_58

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