Sequential/parallel production of potential Malaria vaccines--A direct way from single batch to quasi-continuous integrated production.
An intensification of pharmaceutical protein production processes can be achieved by the integration of unit operations and application of recurring sequences of all biochemical process steps. Within optimization procedures each individual step as well as the overall process has to be in the focus of scientific interest. This paper includes a description of the development of a fully automated production plant, starting with a two step upstream followed by a four step downstream line, including cell clarification, broth cleaning with microfiltration, product concentration with ultrafiltration and purification with column chromatography. Recursive production strategies are developed where a cell breeding, the protein production and the whole downstream is operated in series but also in parallel, each main operation shifted by one day. The quality and reproducibility of the recursive protein expression is monitored on-line by Golden Batch and this is controlled by Model Predictive Multivariate Control (MPMC). As a demonstration process the production of potential Malaria vaccines with Pichia pastoris is under investigation.
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany. Electronic address: reiner.luttmann@haw-hamburg.de.
Reiner
R
Luttmann
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Sven-Oliver
SO
Borchert
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Christian
C
Mueller
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Kai
K
Loegering
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Florian
F
Aupert
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Stephan
S
Weyand
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Christian
C
Kober
Biomedical Primate Research Center, Rijswijk, The Netherlands.
Bart
B
Faber
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Gesine
G
Cornelissen
D019149:Bioreactors; D017780:Malaria Vaccines / Q000096:biosynthesis*; D008962:Models, Theoretical; D010843:Pichia / Q000378:metabolism*; D015203:Reproducibility of Results
D017780:Malaria Vaccines
Golden Batch monitoring; Model predictive multivariate control; Pichia pastoris; Potential Malaria vaccines; Quasi-continuous integrated production; Recursive sequential/parallel processing