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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Karin Westerberg
  • Ernst Broberg Hansen
  • Marcus Degerman
  • Thomas Budde Hansen
  • Bernt Nilsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Chemical Engineering

Keywords

  • Chromatography, Process modeling, Quality by design, Robustness, Sensitivity analysis
Original languageEnglish
Pages (from-to)183-190
JournalChemical Engineering & Technology
Volume35
Issue number1
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes

Related research output

Westerberg, K., 2012, Department of Chemical Engineering, Lund University. 164 p.

Research output: ThesisDoctoral Thesis (compilation)

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