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Model based robustness analysis of an ion-exchange chromatography step
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- Jakobsson, Niklas (author)
- Lund University,Lunds universitet,Avdelningen för kemiteknik,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Chemical Engineering,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Degerman, Marcus (author)
- Lund University,Lunds universitet,Avdelningen för kemiteknik,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Chemical Engineering,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
- Stenborg, Emelie (author)
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- (creator_code:org_t)
- Elsevier BV, 2007
- 2007
- English.
- In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1138:1-2, s. 109-119
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Process development, optimization and robustness analysis for chromatographic separation are often entirely based on experimental work and generic knowledge. This paper describes a model-based approach that can be used to am process knowledge and assist in the robustness analysis of an ion-exchange chromatography step using a model-based approach. A kinetic dispersive model, where the steric mass action model accounts for the adsorption is used to describe column performance. Model calibration is based solely on gradient elution experiments at different gradients, flow rates, pH and column loads. The position and shape of the peaks provide enough information to calibrate the model and thus single-component experiments can be avoided. The model is calibrated to the experiments and the confidence intervals for the estimated parameters are used to account for the model error throughout the analysis. The model is used to predict the result of a robustness analysis conducted as a factorial experiment and to design a robust pooling approach. The confidence intervals are used in a "worst case" approach where the parameters for the components are set at the edge of their confidence intervals to create a worst case for the removal of impurities at each point in the factorial experiment. The pooling limit was changed to ensure product quality at every point in the factorial analysis. The predicted purities and yields were compared to the experimental results to ensure that the prediction intervals cover the experimental results. (c) 2006 Elsevier B.V. All rights reserved.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Kemiteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Chemical Engineering (hsv//eng)
Keyword
- preparative chromatography
- chromatography
- ion-exchange
- simulation
- modeling
- robustness analysis
- validation
- process-scale chromatogaphy
Publication and Content Type
- art (subject category)
- ref (subject category)
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