Applying Mechanistic Models in Bioprocess Development - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 137

Applying Mechanistic Models
in Bioprocess Development

Rita Lencastre Fernandes, Vijaya Krishna Bodla, Magnus Carlquist,
Anna-Lena Heins, Anna Eliasson Lantz, Gürkan Sin and Krist V. Gernaey

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 fermen-
tations are used. The data are described with the well-known model of Sonnleitner
and Käppeli (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.

Keywords Fermentation Identifiability Modeling Monte Carlo PAT
Saccharomyces cerevisiae Sensitivity Uncertainty

R. Lencastre Fernandes V. K. Bodla G. Sin K. V. Gernaey ( )

Department of Chemical and Biochemical Engineering, Technical University of Denmark,
Building 229, 2800 Lyngby, Denmark
e-mail: [e-mail]
M. Carlquist
Division of Applied Microbiology, Department of Chemistry, Lund University,
22100 Lund, Sweden
A.-L. Heins A. E. Lantz
Center for Microbial Biotechnology, Department of Systems Biology,
Technical University of Denmark, Building 223, 2800 Lyngby, Denmark

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