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Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.

Borg, Niklas LU ; Brodsky, Yan; Moscariello, John; Vunnum, Suresh; Vedantham, Ganesh; Westerberg, Karin LU and Nilsson, Bernt LU (2014) In Journal of Chromatography A 1359. p.170-181
Abstract
This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through... (More)
This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through curves or the slight levels of co-elution of the dimer and oligomer with the monomer at higher pH. The model was used to predict how 12 process variations impact the separation. The model is used to establish an elution end collection criterion such that the step can robustly provide the target purity of monomers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chromatography A
volume
1359
pages
170 - 181
publisher
Elsevier
external identifiers
  • pmid:25085821
  • wos:000340984400022
  • scopus:84906060372
ISSN
0021-9673
DOI
10.1016/j.chroma.2014.07.041
language
English
LU publication?
yes
id
929ca80c-6136-41d1-bd34-a1c0cd1eaeaf (old id 4615681)
date added to LUP
2014-09-04 11:18:19
date last changed
2017-11-05 03:17:03
@article{929ca80c-6136-41d1-bd34-a1c0cd1eaeaf,
  abstract     = {This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through curves or the slight levels of co-elution of the dimer and oligomer with the monomer at higher pH. The model was used to predict how 12 process variations impact the separation. The model is used to establish an elution end collection criterion such that the step can robustly provide the target purity of monomers.},
  author       = {Borg, Niklas and Brodsky, Yan and Moscariello, John and Vunnum, Suresh and Vedantham, Ganesh and Westerberg, Karin and Nilsson, Bernt},
  issn         = {0021-9673},
  language     = {eng},
  pages        = {170--181},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography A},
  title        = {Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.},
  url          = {http://dx.doi.org/10.1016/j.chroma.2014.07.041},
  volume       = {1359},
  year         = {2014},
}