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Applying Mechanistic Models in Bioprocess Development

Fernandes, Rita Lencastre ; Bodla, Vijaya Krishna ; Carlquist, Magnus LU ; Heins, Anna-Lena ; Lantz, Anna Eliasson ; Sin, Guerkan and Gernaey, Krist V. (2013) In Advances in Biochemical Engineering, Biotechnology 132. p.137-166
Abstract
The available knowledge on the mechanisms of a bioprocess system is central to process analytical technology. In this respect, mechanistic modeling has gained renewed attention, since a mechanistic model can provide an excellent summary of available process knowledge. Such a model therefore incorporates process-relevant input (critical process variables)-output (product concentration and product quality attributes) relations. The model therefore has great value in planning experiments, or in determining which critical process variables need to be monitored and controlled tightly. Mechanistic models should be combined with proper model analysis tools, such as uncertainty and sensitivity analysis. When assuming distributed inputs, the... (More)
The available knowledge on the mechanisms of a bioprocess system is central to process analytical technology. In this respect, mechanistic modeling has gained renewed attention, since a mechanistic model can provide an excellent summary of available process knowledge. Such a model therefore incorporates process-relevant input (critical process variables)-output (product concentration and product quality attributes) relations. The model therefore has great value in planning experiments, or in determining which critical process variables need to be monitored and controlled tightly. Mechanistic models should be combined with proper model analysis tools, such as uncertainty and sensitivity analysis. When assuming distributed inputs, the resulting uncertainty in the model outputs can be decomposed using sensitivity analysis to determine which input parameters are responsible for the major part of the output uncertainty. Such information can be used as guidance for experimental work; i.e., only parameters with a significant influence on model outputs need to be determined experimentally. The use of mechanistic models and model analysis tools is demonstrated in this chapter. As a practical case study, experimental data from Saccharomyces cerevisiae fermentations are used. The data are described with the well-known model of Sonnleitner and Kappeli (Biotechnol Bioeng 28: 927-937, 1986) and the model is analyzed further. The methods used are generic, and can be transferred easily to other, more complex case studies as well. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Fermentation, Identifiability, Modeling, Monte Carlo, PAT, Saccharomyces, cerevisiae, Sensitivity, Uncertainty
in
Advances in Biochemical Engineering, Biotechnology
volume
132
pages
137 - 166
publisher
Springer
external identifiers
  • wos:000321113100007
  • scopus:84882996157
  • pmid:23307292
ISSN
0724-6145
DOI
10.1007/10_2012_166
language
English
LU publication?
yes
id
3372b676-ade5-4f31-a7df-5ea7210e9cb7 (old id 3987164)
date added to LUP
2016-04-01 14:35:02
date last changed
2022-01-28 01:24:50
@article{3372b676-ade5-4f31-a7df-5ea7210e9cb7,
  abstract     = {{The available knowledge on the mechanisms of a bioprocess system is central to process analytical technology. In this respect, mechanistic modeling has gained renewed attention, since a mechanistic model can provide an excellent summary of available process knowledge. Such a model therefore incorporates process-relevant input (critical process variables)-output (product concentration and product quality attributes) relations. The model therefore has great value in planning experiments, or in determining which critical process variables need to be monitored and controlled tightly. Mechanistic models should be combined with proper model analysis tools, such as uncertainty and sensitivity analysis. When assuming distributed inputs, the resulting uncertainty in the model outputs can be decomposed using sensitivity analysis to determine which input parameters are responsible for the major part of the output uncertainty. Such information can be used as guidance for experimental work; i.e., only parameters with a significant influence on model outputs need to be determined experimentally. The use of mechanistic models and model analysis tools is demonstrated in this chapter. As a practical case study, experimental data from Saccharomyces cerevisiae fermentations are used. The data are described with the well-known model of Sonnleitner and Kappeli (Biotechnol Bioeng 28: 927-937, 1986) and the model is analyzed further. The methods used are generic, and can be transferred easily to other, more complex case studies as well.}},
  author       = {{Fernandes, Rita Lencastre and Bodla, Vijaya Krishna and Carlquist, Magnus and Heins, Anna-Lena and Lantz, Anna Eliasson and Sin, Guerkan and Gernaey, Krist V.}},
  issn         = {{0724-6145}},
  keywords     = {{Fermentation; Identifiability; Modeling; Monte Carlo; PAT; Saccharomyces; cerevisiae; Sensitivity; Uncertainty}},
  language     = {{eng}},
  pages        = {{137--166}},
  publisher    = {{Springer}},
  series       = {{Advances in Biochemical Engineering, Biotechnology}},
  title        = {{Applying Mechanistic Models in Bioprocess Development}},
  url          = {{http://dx.doi.org/10.1007/10_2012_166}},
  doi          = {{10.1007/10_2012_166}},
  volume       = {{132}},
  year         = {{2013}},
}