Constrained optimization of a preparative ion-exchange step for antibody purification
Degerman, Marcus LU ; Jakobsson, Niklas LU and Nilsson, Bernt LU
(2006)
In Journal of Chromatography A
1113(1-2).
p.92-100
- Abstract
- Today, the optimization of chromatographic separation is usually based on experimental work and rule of thumb. The process and analytical technology (PAT) initiative, of the US Food and Drug Administration, has provided the opportunity of using model-based approach when designing downstream processing of pharmaceutical substances. A nonlinear chromatography model was used in this study to optimize a preparative ion-exchange separation step involving two components. Separation was simulated with the general rate model employing Langmuir kinetics. Optimization was performed with an indirect method allowing constraints on the purity, thus avoiding sub-optimization, which can lead to noisy objective functions. The six decision variables used... (More)
- Today, the optimization of chromatographic separation is usually based on experimental work and rule of thumb. The process and analytical technology (PAT) initiative, of the US Food and Drug Administration, has provided the opportunity of using model-based approach when designing downstream processing of pharmaceutical substances. A nonlinear chromatography model was used in this study to optimize a preparative ion-exchange separation step involving two components. Separation was simulated with the general rate model employing Langmuir kinetics. Optimization was performed with an indirect method allowing constraints on the purity, thus avoiding sub-optimization, which can lead to noisy objective functions. The six decision variables used in the optimizations were flow rate, loading volume, initial salt concentration in the elution, final salt concentration in the linear elution gradient and the two cut points. A graphical representation of the effect of the decision variables on the objective function was used to verify that the optimization had converged to the true optimum. The optimal operating points, using productivity and yield separately as objective functions, were found and compared with the product of productivity and yield as objective function. The optimum obtained with this objective function had a lower productivity, than the productivity function, but much higher yield, which makes it a good substitute for a cost function. (c) 2006 Elsevier B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/411158
- author
- Degerman, Marcus
LU
; Jakobsson, Niklas
LU
and Nilsson, Bernt
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- gradient elution nonlinear, constraints, nonlinear constraint, chromatography, simulation, modeling, optimization, downstream processing
- in
- Journal of Chromatography A
- volume
- 1113
- issue
- 1-2
- pages
- 92 - 100
- publisher
- Elsevier
- external identifiers
-
- wos:000236947600012
- pmid:16497317
- scopus:33646013329
- ISSN
- 0021-9673
- DOI
- 10.1016/j.chroma.2006.01.121
- language
- English
- LU publication?
- yes
- id
- 876601cd-fdc5-4322-85bb-79182e23d7b9 (old id 411158)
- date added to LUP
- 2016-04-01 16:16:26
- date last changed
- 2024-11-08 20:58:11
@article{876601cd-fdc5-4322-85bb-79182e23d7b9,
abstract = {{Today, the optimization of chromatographic separation is usually based on experimental work and rule of thumb. The process and analytical technology (PAT) initiative, of the US Food and Drug Administration, has provided the opportunity of using model-based approach when designing downstream processing of pharmaceutical substances. A nonlinear chromatography model was used in this study to optimize a preparative ion-exchange separation step involving two components. Separation was simulated with the general rate model employing Langmuir kinetics. Optimization was performed with an indirect method allowing constraints on the purity, thus avoiding sub-optimization, which can lead to noisy objective functions. The six decision variables used in the optimizations were flow rate, loading volume, initial salt concentration in the elution, final salt concentration in the linear elution gradient and the two cut points. A graphical representation of the effect of the decision variables on the objective function was used to verify that the optimization had converged to the true optimum. The optimal operating points, using productivity and yield separately as objective functions, were found and compared with the product of productivity and yield as objective function. The optimum obtained with this objective function had a lower productivity, than the productivity function, but much higher yield, which makes it a good substitute for a cost function. (c) 2006 Elsevier B.V. All rights reserved.}},
author = {{Degerman, Marcus and Jakobsson, Niklas and Nilsson, Bernt}},
issn = {{0021-9673}},
keywords = {{gradient elution nonlinear; constraints; nonlinear constraint; chromatography; simulation; modeling; optimization; downstream processing}},
language = {{eng}},
number = {{1-2}},
pages = {{92--100}},
publisher = {{Elsevier}},
series = {{Journal of Chromatography A}},
title = {{Constrained optimization of a preparative ion-exchange step for antibody purification}},
url = {{http://dx.doi.org/10.1016/j.chroma.2006.01.121}},
doi = {{10.1016/j.chroma.2006.01.121}},
volume = {{1113}},
year = {{2006}},
}