title: Advanced model-based control strategies for the intensification of upstream and downstream processing in mAb production.
abstract: Current industrial trends encourage the development of sustainable, environmentally friendly processes with minimal energy and material consumption. In particular, the increasing market demand in biopharmaceutical industry and the tight regulations in product quality necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity and lower production costs. This work focuses on the development of advanced control strategies for (i) a cell culture system in a bioreactor and (ii) a semicontinuous purification process. More specifically, we consider a fed-batch culture of GS-NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) for the purification process. The controllers are designed following the PAROC framework/software platform and their capabilities are assessed in silico, against the process models. It is demonstrated that the proposed controllers efficiently manage to increase the system productivity, returning strategies that can lead to continuous, stable process operation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966-988, 2017.
authors.affiliation: Dept. of Chemical Engineering, Centre for Process Systems Engineering (CPSE), Imperial College London, London, SW7 2AZ, U.K.|Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843.
authors.forename: Maria M
authors.identifier: http://orcid.org/0000-0002-8886-0624
authors.initials: MM
authors.lastname: Papathanasiou
authors.affiliation: Dept. of Chemical Engineering, Centre for Process Systems Engineering (CPSE), Imperial College London, London, SW7 2AZ, U.K.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Quiroga-Campano
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, olfgang-Pauli-Str. 10/HCI F 129, W, Zurich, CH-8093, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Steinebach
authors.affiliation: Dept. of Chemical Engineering, Centre for Process Systems Engineering (CPSE), Imperial College London, London, SW7 2AZ, U.K.
authors.forename: Montaña
authors.initials: M
authors.lastname: Elviro
authors.affiliation: Dept. of Chemical Engineering, Centre for Process Systems Engineering (CPSE), Imperial College London, London, SW7 2AZ, U.K.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Mantalaris
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843.
authors.forename: Efstratios N
authors.initials: EN
authors.lastname: Pistikopoulos
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000302:isolation & purification; D019149:Bioreactors; D018929:Cell Culture Techniques; D003198:Computer Simulation; D051379:Mice; D012984:Software; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal
keywords: advanced control; continuous biomanufacturing; monoclonal antibodies; process intensificaiton; process monitoring