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Using computer simulation to assist in the robustness analysis of an ion-exchange chromatography step

Jakobsson, Niklas LU ; Karlsson, David LU ; Axelsson, J P; Zacchi, Guido LU and Nilsson, Bernt LU (2005) In Journal of Chromatography A 1063(1-2). p.99-109
Abstract
This paper presents a methodology to gain process knowledge and assist in the robustness analysis of an ion-exchange step in a protein purification process using a model-based approach. Factorial experimental design is common practice in industry today to obtain robustness characterization of unit operations with respect to variations in process parameters. This work aims at providing a better insight into what process variations affect quality and to further reduce the experimental work to the regions of process variation that are of most interest. This methodology also greatly increases the ability to predict process performance and promotes process understanding. The model calibration part of the methodology involves three consecutive... (More)
This paper presents a methodology to gain process knowledge and assist in the robustness analysis of an ion-exchange step in a protein purification process using a model-based approach. Factorial experimental design is common practice in industry today to obtain robustness characterization of unit operations with respect to variations in process parameters. This work aims at providing a better insight into what process variations affect quality and to further reduce the experimental work to the regions of process variation that are of most interest. This methodology also greatly increases the ability to predict process performance and promotes process understanding. The model calibration part of the methodology involves three consecutive steps to calibrate a steric mass action (SMA) ion-exchange chromatography model. Firstly, a number of gradient elution experiments are performed. Secondly, experimental breakthrough curves have to be generated for the proteins if the adsorption capacity of the medium for each component is not known. Thirdly, a multi-component loading experiment is performed to calibrate the multi-component effects that cannot be determined from the single-component experiments. The separation process studied in this work is the separation of polyclonal IgG from a mixture containing IgG, myoglobin and BSA. The calibrated model is used to simulate six process variations in a full factorial experiment. The results of the simulations provide information about the importance of the different process variations and the simulations are also used to determine the crucial points for the process parameter variations. The methodology can be used to assist in the robustness analysis normally performed in the pharmaceutical industry today as it is able to predict the impact on process performance resulting from variations in salt concentration, column load, protein concentration and flow rate. (C) 2004 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chromatography A
volume
1063
issue
1-2
pages
99 - 109
publisher
Elsevier
external identifiers
  • wos:000226299800011
  • pmid:15700461
  • scopus:11344294824
ISSN
0021-9673
DOI
10.1016/j.chroma.2004.11.067
language
English
LU publication?
yes
id
a610278a-a818-48a6-a8c4-63c37531fa9e (old id 151775)
date added to LUP
2007-06-25 11:56:02
date last changed
2017-10-01 04:40:32
@article{a610278a-a818-48a6-a8c4-63c37531fa9e,
  abstract     = {This paper presents a methodology to gain process knowledge and assist in the robustness analysis of an ion-exchange step in a protein purification process using a model-based approach. Factorial experimental design is common practice in industry today to obtain robustness characterization of unit operations with respect to variations in process parameters. This work aims at providing a better insight into what process variations affect quality and to further reduce the experimental work to the regions of process variation that are of most interest. This methodology also greatly increases the ability to predict process performance and promotes process understanding. The model calibration part of the methodology involves three consecutive steps to calibrate a steric mass action (SMA) ion-exchange chromatography model. Firstly, a number of gradient elution experiments are performed. Secondly, experimental breakthrough curves have to be generated for the proteins if the adsorption capacity of the medium for each component is not known. Thirdly, a multi-component loading experiment is performed to calibrate the multi-component effects that cannot be determined from the single-component experiments. The separation process studied in this work is the separation of polyclonal IgG from a mixture containing IgG, myoglobin and BSA. The calibrated model is used to simulate six process variations in a full factorial experiment. The results of the simulations provide information about the importance of the different process variations and the simulations are also used to determine the crucial points for the process parameter variations. The methodology can be used to assist in the robustness analysis normally performed in the pharmaceutical industry today as it is able to predict the impact on process performance resulting from variations in salt concentration, column load, protein concentration and flow rate. (C) 2004 Elsevier B.V. All rights reserved.},
  author       = {Jakobsson, Niklas and Karlsson, David and Axelsson, J P and Zacchi, Guido and Nilsson, Bernt},
  issn         = {0021-9673},
  language     = {eng},
  number       = {1-2},
  pages        = {99--109},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography A},
  title        = {Using computer simulation to assist in the robustness analysis of an ion-exchange chromatography step},
  url          = {http://dx.doi.org/10.1016/j.chroma.2004.11.067},
  volume       = {1063},
  year         = {2005},
}