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Model-based design and integration of a two-step biopharmaceutical production process.

Otero, Bruno; Degerman, Marcus LU ; Hansen, Thomas Budde; Hansen, Ernst Broberg and Nilsson, Bernt LU (2014) In Bioprocess and Biosystems Engineering 37(10). p.1989-1996
Abstract
This paper presents the design of a two-step process in which the first step is PEGylation of a protein, and the second step is chromatographic purification of the target mono-PEGylated protein from the unreacted and the di-PEGylated impurities. The difference between optimizing each process step separately and optimizing them simultaneously is studied. It was found that by optimizing the steps simultaneously up to a 100 % increase in productivity could be obtained without reduction in yield. Optimizing both steps at the same time makes it possible for the optimization method to take into account that the di-PEGylated protein is much easier to separate than the non-PEGylated protein. The easier separation makes it possible to get a higher... (More)
This paper presents the design of a two-step process in which the first step is PEGylation of a protein, and the second step is chromatographic purification of the target mono-PEGylated protein from the unreacted and the di-PEGylated impurities. The difference between optimizing each process step separately and optimizing them simultaneously is studied. It was found that by optimizing the steps simultaneously up to a 100 % increase in productivity could be obtained without reduction in yield. Optimizing both steps at the same time makes it possible for the optimization method to take into account that the di-PEGylated protein is much easier to separate than the non-PEGylated protein. The easier separation makes it possible to get a higher yield and productivity at the same time. The effect of recycling was also studied and the yield could be increased by 30 % by recycling the unreacted protein. However, if maximum productivity is required, batch mode is preferable. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioprocess and Biosystems Engineering
volume
37
issue
10
pages
1989 - 1996
publisher
Springer
external identifiers
  • pmid:24671271
  • wos:000342171500007
  • scopus:84930709991
ISSN
1615-7605
DOI
10.1007/s00449-014-1174-9
language
English
LU publication?
yes
id
5379c01c-d75b-4ca0-9631-7c4c16b94872 (old id 4379635)
date added to LUP
2014-04-24 12:55:48
date last changed
2017-09-03 03:18:46
@article{5379c01c-d75b-4ca0-9631-7c4c16b94872,
  abstract     = {This paper presents the design of a two-step process in which the first step is PEGylation of a protein, and the second step is chromatographic purification of the target mono-PEGylated protein from the unreacted and the di-PEGylated impurities. The difference between optimizing each process step separately and optimizing them simultaneously is studied. It was found that by optimizing the steps simultaneously up to a 100 % increase in productivity could be obtained without reduction in yield. Optimizing both steps at the same time makes it possible for the optimization method to take into account that the di-PEGylated protein is much easier to separate than the non-PEGylated protein. The easier separation makes it possible to get a higher yield and productivity at the same time. The effect of recycling was also studied and the yield could be increased by 30 % by recycling the unreacted protein. However, if maximum productivity is required, batch mode is preferable.},
  author       = {Otero, Bruno and Degerman, Marcus and Hansen, Thomas Budde and Hansen, Ernst Broberg and Nilsson, Bernt},
  issn         = {1615-7605},
  language     = {eng},
  number       = {10},
  pages        = {1989--1996},
  publisher    = {Springer},
  series       = {Bioprocess and Biosystems Engineering},
  title        = {Model-based design and integration of a two-step biopharmaceutical production process.},
  url          = {http://dx.doi.org/10.1007/s00449-014-1174-9},
  volume       = {37},
  year         = {2014},
}