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Model-Based Process Challenge of an Industrial Ion-Exchange Chromatography Step

Westerberg, Karin LU ; Broberg Hansen, Ernst; Degerman, Marcus LU ; Budde Hansen, Thomas and Nilsson, Bernt LU (2012) In Chemical Engineering & Technology 35(1). p.183-190
Abstract
The separation of one weakly and one strongly binding impurity from a therapeutic protein by ion-exchange chromatography was studied with a mechanistic model. The effect of disturbances in eight potentially critical process parameters on two critical quality attributes was evaluated. It was found that the outgoing concentration of the weakly binding impurity was only affected by the ingoing concentration of this impurity, while the target product purity was affected by the amounts of buffer and acid used to prepare the elution buffers and the protein concentration and purity of the feed. Full factor analysis of these parameters showed that there were interaction effects between the parameters due to the pH dependence of the chromatographic... (More)
The separation of one weakly and one strongly binding impurity from a therapeutic protein by ion-exchange chromatography was studied with a mechanistic model. The effect of disturbances in eight potentially critical process parameters on two critical quality attributes was evaluated. It was found that the outgoing concentration of the weakly binding impurity was only affected by the ingoing concentration of this impurity, while the target product purity was affected by the amounts of buffer and acid used to prepare the elution buffers and the protein concentration and purity of the feed. Full factor analysis of these parameters showed that there were interaction effects between the parameters due to the pH dependence of the chromatographic separation. Sampling-based robustness analysis estimated the probability of batch failure to be above 1?%. The model improved the analysis as it was possible to study the effects of more process parameters and their interactions than would have been possible in an experimental study. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chromatography, Process modeling, Quality by design, Robustness, Sensitivity analysis
in
Chemical Engineering & Technology
volume
35
issue
1
pages
183 - 190
publisher
John Wiley & Sons
external identifiers
  • wos:000298540200018
  • scopus:84855180189
ISSN
1521-4125
DOI
10.1002/ceat.201000560
language
English
LU publication?
yes
id
37225650-13f6-477b-ae3b-e692f13145d9 (old id 2333859)
date added to LUP
2012-01-30 15:54:41
date last changed
2017-10-01 03:03:11
@article{37225650-13f6-477b-ae3b-e692f13145d9,
  abstract     = {The separation of one weakly and one strongly binding impurity from a therapeutic protein by ion-exchange chromatography was studied with a mechanistic model. The effect of disturbances in eight potentially critical process parameters on two critical quality attributes was evaluated. It was found that the outgoing concentration of the weakly binding impurity was only affected by the ingoing concentration of this impurity, while the target product purity was affected by the amounts of buffer and acid used to prepare the elution buffers and the protein concentration and purity of the feed. Full factor analysis of these parameters showed that there were interaction effects between the parameters due to the pH dependence of the chromatographic separation. Sampling-based robustness analysis estimated the probability of batch failure to be above 1?%. The model improved the analysis as it was possible to study the effects of more process parameters and their interactions than would have been possible in an experimental study.},
  author       = {Westerberg, Karin and Broberg Hansen, Ernst and Degerman, Marcus and Budde Hansen, Thomas and Nilsson, Bernt},
  issn         = {1521-4125},
  keyword      = {Chromatography,Process modeling,Quality by design,Robustness,Sensitivity analysis},
  language     = {eng},
  number       = {1},
  pages        = {183--190},
  publisher    = {John Wiley & Sons},
  series       = {Chemical Engineering & Technology},
  title        = {Model-Based Process Challenge of an Industrial Ion-Exchange Chromatography Step},
  url          = {http://dx.doi.org/10.1002/ceat.201000560},
  volume       = {35},
  year         = {2012},
}