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Pooling control in variable preparative chromatography processes.

Westerberg, Karin LU ; Degerman, Marcus LU and Nilsson, Bernt LU (2010) In Bioprocess and Biosystems Engineering 33. p.375-382
Abstract
Preparative chromatographic columns that run at high loads are highly sensitive to batch-to-batch disturbances of the process parameters, placing high demands on the strategy used for pooling of the product fractions. A new approach to pooling control is presented in a proof-of-concept study. A model-based sensitivity analysis was performed identifying the critical process parameters to product purity and optimal cut points. From this, the robust fixed cut points were found and pooling control strategies for variations in the critical parameters were designed. Direct measurements and indirect measurements based on the UV detector signal were used as control signals. The method is demonstrated for two case studies of preparative protein... (More)
Preparative chromatographic columns that run at high loads are highly sensitive to batch-to-batch disturbances of the process parameters, placing high demands on the strategy used for pooling of the product fractions. A new approach to pooling control is presented in a proof-of-concept study. A model-based sensitivity analysis was performed identifying the critical process parameters to product purity and optimal cut points. From this, the robust fixed cut points were found and pooling control strategies for variations in the critical parameters were designed. Direct measurements and indirect measurements based on the UV detector signal were used as control signals. The method is demonstrated for two case studies of preparative protein chromatography: hydrophobic interaction and reversed phase chromatography. The yield improved from 88.18 to 92.88% when changing from fixed to variable pooling in hydrophobic interaction chromatography, and from 35.15 to 76.27% in the highly sensitive reversed phase chromatography. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioprocess and Biosystems Engineering
volume
33
pages
375 - 382
publisher
Springer
external identifiers
  • wos:000274398800010
  • pmid:19513758
  • scopus:77649236686
ISSN
1615-7605
DOI
10.1007/s00449-009-0335-8
language
English
LU publication?
yes
id
a8113e4a-e601-4a0f-afe4-33b19890915f (old id 1434351)
date added to LUP
2016-04-01 14:09:29
date last changed
2023-09-03 10:11:33
@article{a8113e4a-e601-4a0f-afe4-33b19890915f,
  abstract     = {{Preparative chromatographic columns that run at high loads are highly sensitive to batch-to-batch disturbances of the process parameters, placing high demands on the strategy used for pooling of the product fractions. A new approach to pooling control is presented in a proof-of-concept study. A model-based sensitivity analysis was performed identifying the critical process parameters to product purity and optimal cut points. From this, the robust fixed cut points were found and pooling control strategies for variations in the critical parameters were designed. Direct measurements and indirect measurements based on the UV detector signal were used as control signals. The method is demonstrated for two case studies of preparative protein chromatography: hydrophobic interaction and reversed phase chromatography. The yield improved from 88.18 to 92.88% when changing from fixed to variable pooling in hydrophobic interaction chromatography, and from 35.15 to 76.27% in the highly sensitive reversed phase chromatography.}},
  author       = {{Westerberg, Karin and Degerman, Marcus and Nilsson, Bernt}},
  issn         = {{1615-7605}},
  language     = {{eng}},
  pages        = {{375--382}},
  publisher    = {{Springer}},
  series       = {{Bioprocess and Biosystems Engineering}},
  title        = {{Pooling control in variable preparative chromatography processes.}},
  url          = {{http://dx.doi.org/10.1007/s00449-009-0335-8}},
  doi          = {{10.1007/s00449-009-0335-8}},
  volume       = {{33}},
  year         = {{2010}},
}