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Aspects of the Design of Preparative Chromatography for Purification of Antibodies

Karlsson, David LU (2004)
Abstract
The development of biotechnological products is becoming more and more expensive. One type of protein attracting a great deal of attention in the biopharmaceutical industry is antibodies, which was used in this work. The cost of producing antibodies is, however, high, mainly due to the downstream processing, which constitutes 50–80% of the total cost. This work describes model-based methods to design a chromatography purification step and the important underlying physical phenomena. The model used was a general rate model or a reaction dispersive model with two different adsorption descriptions, Langmuir Mobile Phase Modulators and Steric Mass Action.



The diffusion of protein in gels was studied using holographic methods... (More)
The development of biotechnological products is becoming more and more expensive. One type of protein attracting a great deal of attention in the biopharmaceutical industry is antibodies, which was used in this work. The cost of producing antibodies is, however, high, mainly due to the downstream processing, which constitutes 50–80% of the total cost. This work describes model-based methods to design a chromatography purification step and the important underlying physical phenomena. The model used was a general rate model or a reaction dispersive model with two different adsorption descriptions, Langmuir Mobile Phase Modulators and Steric Mass Action.



The diffusion of protein in gels was studied using holographic methods as Electronic Speckle Pattern Interferometry and Holographic Interferometry and also by chromatography breakthrough experiments. The adsorption kinetic data was obtained using chromatography elution experiments with different gradients.



Different methods to calibrate an ion-exchange model were studied. The model was then used to optimise the operating conditions and to perform a model-based robustness analysis. The methods suggested in this thesis are a step towards reducing time for development, capital expenditure and labour costs in the downstream process. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Jungbauer, Alois, Institute für Angewandte Mikrobiologie, Univ. F. Bodenkultur Wien, Muthgasse 18 (House B ), A-1190 WIEN, Austria
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Kemiteknik och kemisk teknologi, ion-exchange chromatography, adsorption kinetics, gels, model calibration, robustness analysis, optimisation, ESPI, diffusion, steric mass action, Langmuir MPM, antibodies, design, Preparative chromatography, modelling, proteins, Chemical technology and engineering
pages
171 pages
publisher
Department of Chemical Engineering, Lund University
defense location
Lecture hall C, Chemical Center, Lund Institute of Technology, Sweden
defense date
2004-05-14 13:30
external identifiers
  • other:ISRN: LUTKDH/(TKKA-1003)/1-92/(2004)
ISSN
1100-2778
ISBN
91-628-6046-1
language
English
LU publication?
yes
id
3f61f107-d988-4647-bc85-90356d77f4d3 (old id 466992)
date added to LUP
2007-10-13 14:13:43
date last changed
2016-09-19 08:44:56
@phdthesis{3f61f107-d988-4647-bc85-90356d77f4d3,
  abstract     = {The development of biotechnological products is becoming more and more expensive. One type of protein attracting a great deal of attention in the biopharmaceutical industry is antibodies, which was used in this work. The cost of producing antibodies is, however, high, mainly due to the downstream processing, which constitutes 50–80% of the total cost. This work describes model-based methods to design a chromatography purification step and the important underlying physical phenomena. The model used was a general rate model or a reaction dispersive model with two different adsorption descriptions, Langmuir Mobile Phase Modulators and Steric Mass Action.<br/><br>
<br/><br>
The diffusion of protein in gels was studied using holographic methods as Electronic Speckle Pattern Interferometry and Holographic Interferometry and also by chromatography breakthrough experiments. The adsorption kinetic data was obtained using chromatography elution experiments with different gradients.<br/><br>
<br/><br>
Different methods to calibrate an ion-exchange model were studied. The model was then used to optimise the operating conditions and to perform a model-based robustness analysis. The methods suggested in this thesis are a step towards reducing time for development, capital expenditure and labour costs in the downstream process.},
  author       = {Karlsson, David},
  isbn         = {91-628-6046-1},
  issn         = {1100-2778},
  keyword      = {Kemiteknik och kemisk teknologi,ion-exchange chromatography,adsorption kinetics,gels,model calibration,robustness analysis,optimisation,ESPI,diffusion,steric mass action,Langmuir MPM,antibodies,design,Preparative chromatography,modelling,proteins,Chemical technology and engineering},
  language     = {eng},
  pages        = {171},
  publisher    = {Department of Chemical Engineering, Lund University},
  school       = {Lund University},
  title        = {Aspects of the Design of Preparative Chromatography for Purification of Antibodies},
  year         = {2004},
}