Using artificial neural networks to accelerate flowsheet optimization for downstream process development

被引:7
作者
Keulen, Daphne [1 ]
van der Hagen, Erik [1 ]
Geldhof, Geoffroy [2 ]
Le Bussy, Olivier [2 ]
Pabst, Martin [1 ]
Ottens, Marcel [1 ]
机构
[1] Delft Univ Technol, Dept Biotechnol, Van der Maasweg 9, NL-2629 HZ Delft, Netherlands
[2] GSK, Tech Res & Dev Microbial Drug Subst, Rixensart, Belgium
关键词
artificial neural networks; chromatography; downstream process development; flowsheet optimization; mechanistic modeling; model-based process optimization; CHROMATOGRAPHY; FRAMEWORK; QUALITY; SYSTEMS; DESIGN;
D O I
10.1002/bit.28454
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
An optimal purification process for biopharmaceutical products is important to meet strict safety regulations, and for economic benefits. To find the global optimum, it is desirable to screen the overall design space. Advanced model-based approaches enable to screen a broad range of the design-space, in contrast to traditional statistical or heuristic-based approaches. Though, chromatographic mechanistic modeling (MM), one of the advanced model-based approaches, can be speed-limiting for flowsheet optimization, which evaluates every purification possibility (e.g., type and order of purification techniques, and their operating conditions). Therefore, we propose to use artificial neural networks (ANNs) during global optimization to select the most optimal flowsheets. So, the number of flowsheets for final local optimization is reduced and consequently the overall optimization time. Employing ANNs during global optimization proved to reduce the number of flowsheets from 15 to only 3. From these three, one flowsheet was optimized locally and similar final results were found when using the global outcome of either the ANN or MM as starting condition. Moreover, the overall flowsheet optimization time was reduced by 50% when using ANNs during global optimization. This approach accelerates the early purification process design; moreover, it is generic, flexible, and regardless of sample material's type.
引用
收藏
页码:2318 / 2331
页数:14
相关论文
共 35 条
  • [1] [Anonymous], 2009, ICH HARMONISED TRIPA
  • [2] Chromatography Process Development in the Quality by Design Paradigm I: Establishing a High-Throughput Process Development Platform as a Tool for Estimating "Characterization Space" for an Ion Exchange Chromatography Step
    Bhambure, R.
    Rathore, A. S.
    [J]. BIOTECHNOLOGY PROGRESS, 2013, 29 (02) : 403 - 414
  • [3] Digital Twins in Pharmaceutical and Biopharmaceutical Manufacturing: A Literature Review
    Chen, Yingjie
    Yang, Ou
    Sampat, Chaitanya
    Bhalode, Pooja
    Ramachandran, Rohit
    Ierapetritou, Marianthi
    [J]. PROCESSES, 2020, 8 (09)
  • [4] Multiple global optima location using differential evolution, clustering, and local search
    Dominico, Gabriel
    Parpinelli, Rafael Stubs
    [J]. APPLIED SOFT COMPUTING, 2021, 108
  • [5] FDA, 2004, PAT GUID IND A FRAM
  • [6] Comparison of the kinetic models of linear chromatography
    Felinger, A
    Guiochon, G
    [J]. CHROMATOGRAPHIA, 2004, 60 (Suppl 1) : S175 - S180
  • [7] Functional nodes in dynamic neural networks for bioprocess modelling
    Fellner, M
    Delgado, A
    Becker, T
    [J]. BIOPROCESS AND BIOSYSTEMS ENGINEERING, 2003, 25 (05) : 263 - 270
  • [8] Model-based integrated optimization and evaluation of a multi-step ion exchange chromatography
    Huuk, Thiemo C.
    Hahn, Tobias
    Osberghaus, Anna
    Hubbuch, Juergen
    [J]. SEPARATION AND PURIFICATION TECHNOLOGY, 2014, 136 : 207 - 222
  • [9] Model-based optimization strategies for chromatographic processes: a review
    Kawajiri, Yoshiaki
    [J]. ADSORPTION-JOURNAL OF THE INTERNATIONAL ADSORPTION SOCIETY, 2021, 27 (01): : 1 - 26
  • [10] Recent advances to accelerate purification process development: A review with a focus on vaccines
    Keulen, Daphne
    Geldhof, Geoffroy
    Le Bussy, Olivier
    Pabst, Martin
    Ottens, Marcel
    [J]. JOURNAL OF CHROMATOGRAPHY A, 2022, 1676