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Journal of Process Control
Vol. 35, 2015, Pages: 113–126

Development and monitoring of an integrated bioprocess for production of a potential malaria vaccine with Pichia pastoris

Sven-Oliver Borchert, Tobias Voss, Fabian Schuetzmeier, Jessica Paul, Gesine Cornelissen, Reiner Luttmann

Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.


An engineered variant of the yeast Pichia pastoris was used to produce the potential malaria vaccine D1M1. This paper describes the implementation of an expanded bed adsorption chromatography step into a sequential cultivation process of the yeast in order to link protein expression, cell release, and product capture of the secreted protein in a fully automated plant. The process is operated with a semi-continuous strategy for an integrated production. Process improvements have been achieved using design of experiments. Resulting purities of product achieved up to 87% with recoveries of 51% in a single downstream operation. Furthermore, a multivariate analysis of historical batch data was used to develop a golden batch model for process monitoring.

Keywords: Design of experiments; Expanded bed adsorption chromatography; Golden batch model; Integrated bioprocess; Multivariate data analysis; Sequential processing.

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