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Model-integrated process development demonstrated on the optimization of a robotic cation exchange step

Osberghaus, Anna; Drechsel, Katharina; Hansen, Sigrid; Hepbildikler, Stefan; Nath, Susanne; Haindl, Markus; Lieres, Eric von; Hubbuch, Jürgen

Abstract:
The search for a favorable and robust operating point of a separation process represents a complex multi-factor optimization problem. This problem is typically tackled by design of experiments (DoE) in the factor space and empiric response surface modeling (RSM); however, separation optimizations based on mechanistic modeling are on the rise. In this paper, a DoE–RSM-approach and a mechanistic modeling approach are compared with respect to their performance and predictive power by means of a case study – the optimization of a multicomponent separation of proteins in an ion exchange chromatography step with a nonlinear gradient (ribonuclease A, cytochrome c and lysozyme on SP Sepharose FF). The results revealed that at least for complex problems with low robustness, the performance of the DoE-approach is significantly inferior to the performance of the mechanistic model. While some influential factors of the system could be detected with the DoE–RSM-approach, predictions concerning the peak resolutions were mostly inaccurate and the optimization failed. The predictions of the mechanistic model for separa ... mehr


Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Jahr 2012
Sprache Englisch
Identifikator DOI: 10.1016/j.ces.2012.04.004
ISSN: 0009-2509
KITopen ID: 1000046693
Erschienen in Chemical Engineering Science
Band 76
Seiten 129-139
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