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Advanced model‐based control strategies for the intensification of upstream and downstream processing in mAb production
Authors:Maria M. Papathanasiou  Ana L. Quiroga‐Campano  Fabian Steinebach  Montaña Elviro  Athanasios Mantalaris  Efstratios N. Pistikopoulos
Affiliation:1. Dept. of Chemical Engineering, Centre for Process Systems Engineering (CPSE), Imperial College London, London, U.K;2. Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX;3. Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland
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
Keywords:process intensificaiton  continuous biomanufacturing  advanced control  process monitoring  monoclonal antibodies
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