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Designing robust preparative purification processes with high performance

Degerman, Marcus LU ; Jakobsson, Niklas LU and Nilsson, Bernt LU (2008) In Chemical Engineering & Technology 31(6). p.875-882
Abstract
In the production of pharmaceutical drugs, a large part of the production costs stem from the downstream processing and the chromatographic purifications required. In order to reduce purification costs the process performance must be increased, which means that the processes need to be less robust since robustness comes with the price of lower process performance, and thus, higher production costs. It is difficult to find a good estimate of the robustness of a process experimentally, and therefore, the pharmaceutical industry has been forced to design processes to be very robust. This work presents a model-based method for optimizing purification processes both with regard to performance and robustness. A model of chromatographic processes... (More)
In the production of pharmaceutical drugs, a large part of the production costs stem from the downstream processing and the chromatographic purifications required. In order to reduce purification costs the process performance must be increased, which means that the processes need to be less robust since robustness comes with the price of lower process performance, and thus, higher production costs. It is difficult to find a good estimate of the robustness of a process experimentally, and therefore, the pharmaceutical industry has been forced to design processes to be very robust. This work presents a model-based method for optimizing purification processes both with regard to performance and robustness. A model of chromatographic processes and methods of calibration are presented. The model is then used to determine the operating conditions with highest performance when robustness is not taken into account. With this as a starting point, the process is then optimized for higher robustness and lower probability of batch failure. The purification of Immunoglobulin G through ion exchange chromatography is used to demonstrate the method. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
robustness, purification, modeling, optimization
in
Chemical Engineering & Technology
volume
31
issue
6
pages
875 - 882
publisher
John Wiley & Sons
external identifiers
  • wos:000257036100008
  • scopus:46049094400
ISSN
1521-4125
DOI
10.1002/ceat.200800097
language
English
LU publication?
yes
id
5340287d-4208-4aae-8a9d-f901c25482ee (old id 1187077)
date added to LUP
2008-09-05 08:36:05
date last changed
2017-07-30 03:42:21
@article{5340287d-4208-4aae-8a9d-f901c25482ee,
  abstract     = {In the production of pharmaceutical drugs, a large part of the production costs stem from the downstream processing and the chromatographic purifications required. In order to reduce purification costs the process performance must be increased, which means that the processes need to be less robust since robustness comes with the price of lower process performance, and thus, higher production costs. It is difficult to find a good estimate of the robustness of a process experimentally, and therefore, the pharmaceutical industry has been forced to design processes to be very robust. This work presents a model-based method for optimizing purification processes both with regard to performance and robustness. A model of chromatographic processes and methods of calibration are presented. The model is then used to determine the operating conditions with highest performance when robustness is not taken into account. With this as a starting point, the process is then optimized for higher robustness and lower probability of batch failure. The purification of Immunoglobulin G through ion exchange chromatography is used to demonstrate the method.},
  author       = {Degerman, Marcus and Jakobsson, Niklas and Nilsson, Bernt},
  issn         = {1521-4125},
  keyword      = {robustness,purification,modeling,optimization},
  language     = {eng},
  number       = {6},
  pages        = {875--882},
  publisher    = {John Wiley & Sons},
  series       = {Chemical Engineering & Technology},
  title        = {Designing robust preparative purification processes with high performance},
  url          = {http://dx.doi.org/10.1002/ceat.200800097},
  volume       = {31},
  year         = {2008},
}