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Model-Based Comparison of Antibody Dimerization in Continuous and Batch-Wise Downstream Processing

Sellberg, Anton LU ; Ojala, Frida LU and Nilsson, Bernt LU (2015) In Antibodies 4(3). p.157-169
Abstract
Monoclonal antibodies are generally produced using a generic platform approach in which several chromatographic separations assure high purity of the product. Dimerization can occur during the fermentation stage and may occur also during the downstream processing. We present here simulations in which a traditional platform approach that consist of protein A capture, followed by cation-exchange and anion-exchange chromatography for polishing is compared to a continuous platform in which dimer removal and virus inactivation are carried out on a size-exclusion column. A dimerization model that takes pH, salt concentration and the concentration of antibodies into account is combined with chromatographic models, to be able to predicted both the... (More)
Monoclonal antibodies are generally produced using a generic platform approach in which several chromatographic separations assure high purity of the product. Dimerization can occur during the fermentation stage and may occur also during the downstream processing. We present here simulations in which a traditional platform approach that consist of protein A capture, followed by cation-exchange and anion-exchange chromatography for polishing is compared to a continuous platform in which dimer removal and virus inactivation are carried out on a size-exclusion column. A dimerization model that takes pH, salt concentration and the concentration of antibodies into account is combined with chromatographic models, to be able to predicted both the separation and the degree to which dimers are formed. Purification of a feed composition that contained 1% by weight of dimer and a total antibody concentration of 1 g/L was modeled using both approaches, and the amount of antibodies in the continuous platform was at least 4 times lower than in the traditional platform. The total processing time was also lower, as the cation-exchange polish could be omitted. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Antibodies
volume
4
issue
3
pages
157 - 169
publisher
MDPI AG
external identifiers
  • wos:000364227100002
ISSN
2073-4468
DOI
10.3390/antib4030157
language
English
LU publication?
yes
id
a4352d70-c090-4fff-bacd-3e571a63b055 (old id 7936194)
date added to LUP
2015-09-22 07:01:23
date last changed
2016-04-16 00:22:50
@article{a4352d70-c090-4fff-bacd-3e571a63b055,
  abstract     = {Monoclonal antibodies are generally produced using a generic platform approach in which several chromatographic separations assure high purity of the product. Dimerization can occur during the fermentation stage and may occur also during the downstream processing. We present here simulations in which a traditional platform approach that consist of protein A capture, followed by cation-exchange and anion-exchange chromatography for polishing is compared to a continuous platform in which dimer removal and virus inactivation are carried out on a size-exclusion column. A dimerization model that takes pH, salt concentration and the concentration of antibodies into account is combined with chromatographic models, to be able to predicted both the separation and the degree to which dimers are formed. Purification of a feed composition that contained 1% by weight of dimer and a total antibody concentration of 1 g/L was modeled using both approaches, and the amount of antibodies in the continuous platform was at least 4 times lower than in the traditional platform. The total processing time was also lower, as the cation-exchange polish could be omitted.},
  author       = {Sellberg, Anton and Ojala, Frida and Nilsson, Bernt},
  issn         = {2073-4468},
  language     = {eng},
  number       = {3},
  pages        = {157--169},
  publisher    = {MDPI AG},
  series       = {Antibodies},
  title        = {Model-Based Comparison of Antibody Dimerization in Continuous and Batch-Wise Downstream Processing},
  url          = {http://dx.doi.org/10.3390/antib4030157},
  volume       = {4},
  year         = {2015},
}