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Model based robustness analysis of an ion-exchange chromatography step

Jakobsson, Niklas LU ; Degerman, Marcus LU ; Stenborg, Emelie and Nilsson, Bernt LU (2007) In Journal of Chromatography A 1138(1-2). p.109-119
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
preparative chromatography, chromatography, ion-exchange, simulation, modeling, robustness analysis, validation, process-scale chromatogaphy
in
Journal of Chromatography A
volume
1138
issue
1-2
pages
109 - 119
publisher
Elsevier
external identifiers
  • wos:000243492800014
  • scopus:33845430022
ISSN
0021-9673
DOI
10.1016/j.chroma.2006.10.057
language
English
LU publication?
yes
id
d5e2f89a-a91d-4ba7-8941-a651e497b6e9 (old id 677334)
date added to LUP
2007-12-13 10:11:48
date last changed
2017-09-17 07:08:50
@article{d5e2f89a-a91d-4ba7-8941-a651e497b6e9,
  abstract     = {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.},
  author       = {Jakobsson, Niklas and Degerman, Marcus and Stenborg, Emelie and Nilsson, Bernt},
  issn         = {0021-9673},
  keyword      = {preparative chromatography,chromatography,ion-exchange,simulation,modeling,robustness analysis,validation,process-scale chromatogaphy},
  language     = {eng},
  number       = {1-2},
  pages        = {109--119},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography A},
  title        = {Model based robustness analysis of an ion-exchange chromatography step},
  url          = {http://dx.doi.org/10.1016/j.chroma.2006.10.057},
  volume       = {1138},
  year         = {2007},
}