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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 13:30:00
external identifiers
  • other:ISRN: LUTKDH/(TKKA-1003)/1-92/(2004)
ISBN
91-628-6046-1
language
English
LU publication?
yes
additional info
Article: This thesis is based on the following papers, which is referred to by their roman numerals. Article: I.Charlotte Mattisson, David Karlsson, Sven- Göran Pettersson, Guido Zacchi and Anders Axelsson. Article: Light Deflection and Convection in Diffusion Experiments using Holographic Interferometry, Journal of Physics D: Applied Physics, 2001, 34, 3088-3096 Article: II.David Karlsson, Guido Zacchi and Anders Axelsson. Article: Electronic Speckle Pattern Interferometry: A Tool for Determining Diffusion and Partition Coefficients for Proteins in Gels, Biotechnology Progress, , 2002, 18(6), 1423-1430 Article: III.David Karlsson, Niklas Jakobsson, Karl-Johan Brink, Anders Axelsson and Bernt Nilsson. Article: Methodologies for Model Calibration to Assist the Design of a Preparative Ion-Exchange Step for Antibody Purification, Journal of Chromatography A, 2004, 1033(1), 69-80 Article: IV.David Karlsson, Niklas Jakobsson, Anders Axelsson and Bernt Nilsson. Article: Model-Based Optimization of a Preparative Ion-Exchange Step for Antibody Purification, Journal of Chromatography A, 2004, Submitted Article: V.Niklas Jakobsson, David Karlsson, Jan-Peter Axelsson, Guido Zacchi and Bernt Nilsson. Article: Using Computer Simulation to Assist the Robustness Analysis of an Ion Exchange Chromatography Step, Journal of Chromatography A, 2004, Manuscript
id
3f61f107-d988-4647-bc85-90356d77f4d3 (old id 466992)
date added to LUP
2016-04-01 16:26:12
date last changed
2018-11-21 20:41:23
@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},
  language     = {eng},
  publisher    = {Department of Chemical Engineering, Lund University},
  school       = {Lund University},
  title        = {Aspects of the Design of Preparative Chromatography for Purification of Antibodies},
  year         = {2004},
}