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

被引:34
作者
Papathanasiou, Maria M. [1 ,2 ]
Quiroga-Campano, Ana L. [1 ]
Steinebach, Fabian [3 ]
Elviro, Montana [1 ]
Mantalaris, Athanasios [1 ]
Pistikopoulos, Efstratios N. [2 ,4 ]
机构
[1] Imperial Coll London, Ctr Proc Syst Engn, Dept Chem Engn, London SW7 2AZ, England
[2] Texas A&M Univ, Artie McFerrin Dept Chem Engn, College Stn, TX 77843 USA
[3] ETH, Inst Chem & Bioengn, Olfgang Pauli Str 10 HCI F 129, CH-8093 Zurich, Switzerland
[4] Univ Salamanca, Sch Chem Sci, Dept Chem Engn, Plaza Caidos 1-5, E-37008 Salamanca, Spain
关键词
process intensificaiton; continuous biomanufacturing; advanced control; process monitoring; monoclonal antibodies; RECOMBINANT PROTEIN-PRODUCTION; GRADIENT PURIFICATION MCSGP; MONOCLONAL-ANTIBODIES; PREDICTIVE CONTROL; MAMMALIAN-CELLS; PROCESS SYSTEMS; BATCH CULTURE; LOOP CONTROL; METABOLISM; OPTIMIZATION;
D O I
10.1002/btpr.2483
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. (C) 2017 American Institute of Chemical Engineers
引用
收藏
页码:966 / 988
页数:23
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