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Antibodies 2017, 6(4), 21; https://doi.org/10.3390/antib6040021

Integration of Aqueous Two-Phase Extraction as Cell Harvest and Capture Operation in the Manufacturing Process of Monoclonal Antibodies

1
Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, 38678 Clausthal-Zellerfeld, Germany
2
Boehringer Ingelheim Pharma GmbH & Co. KG, Bioprocess + Pharma. Dev. Biologicals, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany
*
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 17 November 2017 / Accepted: 20 November 2017 / Published: 1 December 2017
(This article belongs to the Special Issue Monoclonal Antibodies)
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Abstract

Substantial improvements have been made to cell culturing processes (e.g., higher product titer) in recent years by raising cell densities and optimizing cultivation time. However, this has been accompanied by an increase in product-related impurities and therefore greater challenges in subsequent clarification and capture operations. Considering the paradigm shift towards the design of continuously operating dedicated plants at smaller scales—with or without disposable technology—for treating smaller patient populations due to new indications or personalized medicine approaches, the rising need for new, innovative strategies for both clarification and capture technology becomes evident. Aqueous two-phase extraction (ATPE) is now considered to be a feasible unit operation, e.g., for the capture of monoclonal antibodies or recombinant proteins. However, most of the published work so far investigates the applicability of ATPE in antibody-manufacturing processes at the lab-scale and for the most part, only during the capture step. This work shows the integration of ATPE as a combined harvest and capture step into a downstream process. Additionally, a model is applied that allows early prediction of settler dimensions with high prediction accuracy. Finally, a reliable process development concept, which guides through the necessary steps, starting from the definition of the separation task to the final stages of integration and scale-up, is presented. View Full-Text
Keywords: interfacial partitioning; cell harvest; capture; aqueous two-phase extraction; horizontal settler; static mixer; process integration; continuous phase separation interfacial partitioning; cell harvest; capture; aqueous two-phase extraction; horizontal settler; static mixer; process integration; continuous phase separation
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Schmidt, A.; Richter, M.; Rudolph, F.; Strube, J. Integration of Aqueous Two-Phase Extraction as Cell Harvest and Capture Operation in the Manufacturing Process of Monoclonal Antibodies. Antibodies 2017, 6, 21.

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