Development and monitoring of an integrated bioprocess for production of a potential malaria vaccine with Pichia pastoris. (November 2015)

• Record Type: Journal Article
• Authors: Borchert, Sven-Oliver; Voss, Tobias; Schuetzmeier, Fabian; Paul, Jessica; Cornelissen, Gesine; Luttmann, Reiner
• Is Part Of: Journal of process control. Volume 35(2015:Nov.)
• Page Start: 113
• Page End: 126
• Publication Date: 2015-11
• Subjects: AMA1 apical membrane antigen 1 -- BMBF German Federal Ministry of Education and Research -- BPRC Biomedical Primate Research Center -- BWF Hamburg Ministry of Science and Research -- CCC central composite circumscribed -- CV column volume -- D1M1 fusion protein composed of AMA1 and MSP1 -- DModX distance to model -- DoE design of experiments -- EBA expanded bed adsorption -- FDA Food and Drug Administration -- FF fast flow -- FPLC fast protein liquid chromatography -- gb golden batch -- HPLC high performance liquid chromatography -- IMAC immobilized metal affinity chromatography -- ISPR in situ product removal -- MLR multiple linear regression -- MPCA multiway principle component analysis -- MSP1 merozoite surface protein 1 -- MV model validity -- MVDA multivariate data analysis -- NIPALS non-linear iterative partial least squares -- PAGE polyacrylamide gel electrophoresis -- PAT process analytical technology -- PCA principal component analysis -- PLS projection to latent structures -- PS prediction set -- Q2 goodness of prediction -- QbD quality by design -- R2 goodness of fit -- RP reproducibility -- RQ respiratory quotient -- SCADA supervisory control and data aquisition -- SD standard deviation -- SDS sodium dodecyl sulfate; Design of experiments -- Expanded bed adsorption chromatography -- Golden batch model -- Integrated bioprocess -- Multivariate data analysis -- Sequential processing; Process control -- Periodicals; Fabrication -- Contrôle -- Périodiques; Process control; Periodicals; Electronic journals; 660.281
• DOI: 10.1016/j.jprocont.2015.08.006
• Languages: English
• ISSNs: 0959-1524

Abstract

Highlights: Pichia pastoris was used for expression of a potential malaria vaccine. An integrated bioprocess with expanded bed adsorption was set up. Design of experiments was applied successfully for process optimization. A golden batch model for monitoring of the integrated process was constructed. Abstract: 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.