The development of an industrial-scale fed-batch fermentation simulation

Goldrick, Stephen; Ştefan, Andrei; Lovett, David; Montague, G.A.; Lennox, Barry

doi:10.1016/j.jbiotec.2014.10.029

Cited by 82 publications

(41 citation statements)

References 50 publications

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“…Batch and fed-batch-operated processes are predominantly used in the industry, although perfusion processes have been proven for certain applications to be of higher advantage, for example, when fragile and highly glycosylated products are involved [19][20][21]. In principle, the reactor content is supplemented with nutrients during fed-batch cultivations.…”

Section: Process and Control Strategiesmentioning

confidence: 99%

Model-Based Design of Process Strategies for Cell Culture Bioprocesses: State of the Art and New Perspectives

Pörtner¹

2017

New Insights Into Cell Culture Technology

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Production processes for biopharmaceuticals with mammalian cells have to provide a nearly optimal environment to promote cell growth and product formation. Design and operation of a bioreactor are complex tasks, not only with respect to reactor configuration and size but also with respect to the mode of operation. New concepts for the design and layout of process strategies are required to meet regulatory demands and to guarantee efficient, safe, and reproducible biopharmaceutical production. Key elements are critical process parameters (CPPs), which affect critical quality attributes (CQAs), quality by design (QbD), process analytical tools (PAT), and design of experiment (DoE). In this chapter, some fundamentals including process and control strategies as well as concepts for process development are discussed. Examples for novel model-based concepts for the design of experiments to identify suitable fed-batch-feeding strategies are shown.

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Section: Process and Control Strategiesmentioning

confidence: 99%

Model-Based Design of Process Strategies for Cell Culture Bioprocesses: State of the Art and New Perspectives

Pörtner¹

2017

New Insights Into Cell Culture Technology

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“…The process is a multiphase bio-process with nonlinear dynamics. This study uses the industrial-scale fed-batch fermentation simulator developed by Goldrick et al (2015). The work is an extension of the structured penicillin fermentation model developed by Paul and Thomas (1996) and describes all the component balances relating to the process variables.…”

Section: Case Study Of An Industrial Penicillin Fermentation Processmentioning

confidence: 99%

“…The evolution of centered and scaled variables used in the analysis is shown in Figures 5 and 6. Detailed operating procedure and descriptions of the reactor is available in Goldrick et al (2015).…”

Section: Case Study Of An Industrial Penicillin Fermentation Processmentioning

confidence: 99%

Batch Process Monitoring Based on Fuzzy Segmentation of Multivariate Time-Series

Tanatavikorn

Yamashita

2017

J. Chem. Eng. Japan / JCEJ

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This paper proposes a novel batch process monitoring method called adjoined time series principal component analysis (AdTsPCA). In this method, a modi ed GG clustering is used for phase identi cation and data segmentation and multiple time-ordered overlapping PCA models are constructed from the data segments. The PCA models are then used for statistical process monitoring. The key characteristic of AdTsPCA is that additional information contained in the order of PCA models allows for additional diagnosis by the comparison of known process phase and suspected abnormal situation. The proposed AdTsPCA is applied to an industrial penicillin fermentation process to illustrate the e ectiveness of the method. AdTsPCA is able to detect faults in the process and signi cantly reduces the number of false positive errors in the process monitoring.

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“…These include mechanistic techniques [4] and linear and non-linear empirical techniques. Empirical models are typically easier to develop and more accurate for large-scale systems, where there is an incomplete understanding of the fundamental dynamics of the process.…”

Section: Introductionmentioning

confidence: 99%

Multivariate batch to batch optimisation of fermentation processes incorporating validity constraints

Duran-Villalobos

Lennox

Lauri

2016

Journal of Process Control

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This paper presents an innovative optimisation technique, which utilises an adaptive Multiway Partial Least Squares (MPLS) model to track the dynamics of a batch process from one batch to the next. Utilising this model, an optimisation algorithm solves a quadratic cost function that identifies operating conditions for the subsequent batch that should increase yield. Hard constraints are shown to be required when solving the cost function to ensure that batch conditions do not vary too greatly from one batch to the next. Furthermore, validity constraints are imposed to prevent the PLS model from extrapolating significantly when determining new operating conditions. The capabilities of the proposed technique are illustrated through its application to two benchmark fermentation simulations, where its performance is shown to compare favourably with alternative batch-to-batch optimisation techniques.

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The development of an industrial-scale fed-batch fermentation simulation

Cited by 82 publications

References 50 publications

Model-Based Design of Process Strategies for Cell Culture Bioprocesses: State of the Art and New Perspectives

Model-Based Design of Process Strategies for Cell Culture Bioprocesses: State of the Art and New Perspectives

Batch Process Monitoring Based on Fuzzy Segmentation of Multivariate Time-Series

Multivariate batch to batch optimisation of fermentation processes incorporating validity constraints

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