Advanced Model-Based Control Strategies for the Intensification of Upstream and Downstream Processing in mAb Production

作者：Papathanasiou Maria M; Quiroga Campano Ana L; Steinebach Fabian; Elviro Montana; Mantalaris Athanasios; Pistikopoulos Efstratios N^*

来源：Biotechnology Progress, 2017, 33(4): 966-988.

DOI：10.1002/btpr.2483

• process intensificaiton
• continuous biomanufacturing
• advanced control
• process monitoring
• monoclonal antibodies

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.

• 出版日期2017-8