Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4615681
- author
- Borg, Niklas LU ; Brodsky, Yan ; Moscariello, John ; Vunnum, Suresh ; Vedantham, Ganesh ; Westerberg, Karin LU and Nilsson, Bernt LU
- organization
- publishing date
- 2014
- 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
- 2016-04-01 10:41:34
- date last changed
- 2023-12-09 00:46:41
@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}},
doi = {{10.1016/j.chroma.2014.07.041}},
volume = {{1359}},
year = {{2014}},
}