Cited by 362Fluid Dynamics and MixingMicrobial Metabolic Engineering and BioproductionViral Infectious Diseases and Gene Expression in Insects

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Optimization and scale up of industrial fermentation processes

Schmidt, F. R.·2005·Applied Microbiology and Biotechnology

DOI 10.1007/s00253-005-0003-0

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Abstract

To increase product yields and to ensure consistent product quality, key issues of industrial fermentations, process optimization and scale up are aimed at maintaining optimum and homogenous reaction conditions minimizing microbial stress exposure and enhancing metabolic accuracy. For each individual product, process and facility, suitable strategies have to be elaborated by a comprehensive and detailed process characterization, identification of the most relevant process parameters influencing product yield and quality and their establishment as scale-up parameters to be kept constant as far as possible. Physical variables, which can only be restrictedly kept constant as single parameters, may be combined with other pertinent parameters to appropriate mathematical groups or dimensionless terms. Process characterization is preferably based on real-time or near real-time data collected by in situ and on-line measurements and may be facilitated by supportive approaches and tools like neural network based chemometric data analysis and modelling, clarification of the mixing and stream conditions through computational fluid dynamics and scale-down simulations. However, as fermentation facilities usually are not strictly designed according to scale-up criteria and the process conditions in the culture vessels thus may differ significantly and since any strategy and model can only insufficiently consider and reflect the highly complex interdependence and mutual interaction of fermentation parameters, successful scale up in most cases is not the result of a conclusive and straight-lined experimental strategy, but rather will be the outcome of a separate process development and optimization on each scale. This article gives an overview on the problems typically coming along with fermentation process optimization and scale up, and presents currently applied scale-up strategies while considering future technologies, with emphasis on Escherichia coli as one of the most commonly fermented organisms.

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Authors: Schmidt, F. R.
Affiliations: Sanofi (Germany) (DE)
Corresponding author: Schmidt, F. R.
Venue: Applied Microbiology and Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2005-07-07
Volume: 68
Issue: 4
Pages: 425-435
ISSN: 0175-7598 (ISSN-L)
1432-0614
DOI: 10.1007/s00253-005-0003-0
OpenAlex: W2024244058
Cited by: 362
References: 100
Citations by year: 2026: 23 · 2025: 37 · 2024: 29 · 2023: 25 · 2022: 20 · 2021: 18 · 2020: 24 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 19 · 2015: 12 · 2014: 12 · 2013: 12 · 2012: 17
FWCI: 0.67
Type: journal article
Language: en
Update notices: erratum (2005-10-01)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Applied Microbiology and Biotechnology (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Fluid Dynamics and Mixing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords: industrial fermentation, process optimization, scale-up, process characterization, microbial stress, product yield, product quality, in situ monitoring, online measurement, chemometrics, artificial neural networks, computational fluid dynamics, Escherichia coli, dimensionless parameters
MeSH terms: Computer Simulation, Facility Design and Construction, Fermentation, Industrial Microbiology, Cell Culture Techniques, Bioreactors

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Optimization and scale up of industrial fermentation processes

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