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Application of Global Sensitivity Analysis to Determine Goals for Design of Experiments: An Example Study on Antibody-Producing Cell Cultures

Authors

  • Cleo Kontoravdi,

    1. Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom
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  • Steven P. Asprey,

    1. Orbis Investment Advisory Ltd., Orbis House, 5 Mansfield Street W1G 9NG, United Kingdom
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  • Efstratios N. Pistikopoulos,

    1. Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom
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  • Athanasios Mantalaris

    Corresponding author
    1. Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom
    • Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom. Tel: +44 20 7594 5601. Fax: +44 20 7594 5604
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Abstract

Global sensitivity analysis (GSA) can be used to quantify the importance of model parameters and their interactions with respect to model output. In this study, the Sobol′ method for GSA is applied to a dynamic model of monoclonal antibody-producing mammalian cell cultures in order to identify the parameters that need to be accurately determined experimentally. Our results show that most parameters have low sensitivity indices and exhibit strong interactions with one another. These parameters can be set at their nominal values and unnecessary experimentation can therefore be avoided. In contrast, certain parameters are identified as sensitive, necessitating their estimation given sufficiently rich experimental data. Moreover, parameter sensitivity varies during culture time in a biologically meaningful manner. In conclusion, GSA can serve as an excellent precursor to optimal experiment design.

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