title: Optimization of biopharmaceutical downstream processes supported by mechanistic models and artificial neural networks.
abstract: Downstream process development is a major area of importance within the field of bioengineering. During the design of such a downstream process, important decisions have to be made regarding the type of unit operations as well as their sequence and their operating conditions. Current computational approaches addressing these issues either show a high level of simplification or struggle with computational speed. Therefore, this article presents a new approach that combines detailed mechanistic models and speed-enhancing artificial neural networks. This approach was able to simultaneously optimize a process with three different chromatographic columns toward yield with a minimum purity of 99.9%. The addition of artificial neural networks greatly accelerated this optimization. Due to high computational speed, the approach is easily extendable to include more unit operations. Therefore, it can be of great help in the acceleration of downstream process development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:696-707, 2017.
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Pirrung
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.
authors.forename: Luuk A M
authors.initials: LAM
authors.lastname: van der Wielen
authors.affiliation: DSM Biotechnology Center, Alexander Fleminglaan 1, 2613 AX Delft, The Netherlands.
authors.forename: Ruud F W C
authors.initials: RFWC
authors.lastname: van Beckhoven
authors.affiliation: DSM Biotechnology Center, Alexander Fleminglaan 1, 2613 AX Delft, The Netherlands.
authors.forename: Emile J A X
authors.initials: EJAX
authors.lastname: van de Sandt
authors.affiliation: Synthon Biopharmaceuticals B.V, Microweg 22, 6503 GN Nijmegen, The Netherlands.
authors.forename: Michel H M
authors.initials: MHM
authors.lastname: Eppink
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ottens
mesh_terms: D002845:Chromatography; D016571:Neural Networks, Computer
keywords: chromatography; downstream processing; model-based process development approach; purification process synthesis