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Optimal loading flow rate trajectory in monoclonal antibody capture chromatography

Gomis-Fons, Joaquín LU ; Yamanee-Nolin, Mikael LU ; Andersson, Niklas LU orcid and Nilsson, Bernt LU (2021) In Journal of Chromatography A 1635.
Abstract

In this paper, we determined the optimal flow rate trajectory during the loading phase of a mAb capture column. For this purpose, a multi-objective function was used, consisting of productivity and resin utilization. Several general types of trajectories were considered, and the optimal Pareto points were obtained for all of them. In particular, the presented trajectories include a constant-flow loading process as a nominal approach, a stepwise trajectory, and a linear trajectory. Selected trajectories were then applied in experiments with the state-of-the-art protein A resin mAb Select PrismATM, running in batch mode on a standard single-column chromatography setup, and using both a purified mAb solution as well as a... (More)

In this paper, we determined the optimal flow rate trajectory during the loading phase of a mAb capture column. For this purpose, a multi-objective function was used, consisting of productivity and resin utilization. Several general types of trajectories were considered, and the optimal Pareto points were obtained for all of them. In particular, the presented trajectories include a constant-flow loading process as a nominal approach, a stepwise trajectory, and a linear trajectory. Selected trajectories were then applied in experiments with the state-of-the-art protein A resin mAb Select PrismATM, running in batch mode on a standard single-column chromatography setup, and using both a purified mAb solution as well as a clarified supernatant. The results show that this simple approach, programming the volumetric flow rate according to either of the explored strategies, can improve the process economics by increasing productivity by up to 12% and resin utilization by up to 9% compared to a constant-flow process, while obtaining a yield higher than 99%. The productivity values were similar to the ones obtained in a multi-column continuous process, and ranged from 0.23 to 0.35 mg/min/mL resin. Additionally, it is shown that a model calibration carried out at constant flow can be applied in the simulation and optimization of flow trajectories. The selected processes were scaled up to pilot scale and simulated to prove that even higher productivity and resin utilization can be achieved at larger scales, and therefore confirm that the trajectories are generalizable across process scales for this resin.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chromatography scale-up, Flow programming, Flow trajectory, Monoclonal antibody, Multi-objective optimization, Protein A chromatography
in
Journal of Chromatography A
volume
1635
article number
461760
publisher
Elsevier
external identifiers
  • pmid:33271430
  • scopus:85097334782
ISSN
0021-9673
DOI
10.1016/j.chroma.2020.461760
language
English
LU publication?
yes
id
0dc9ba8d-f9ec-4daa-9178-43a2ff850942
date added to LUP
2020-12-21 11:44:39
date last changed
2024-05-30 01:47:18
@article{0dc9ba8d-f9ec-4daa-9178-43a2ff850942,
  abstract     = {{<p>In this paper, we determined the optimal flow rate trajectory during the loading phase of a mAb capture column. For this purpose, a multi-objective function was used, consisting of productivity and resin utilization. Several general types of trajectories were considered, and the optimal Pareto points were obtained for all of them. In particular, the presented trajectories include a constant-flow loading process as a nominal approach, a stepwise trajectory, and a linear trajectory. Selected trajectories were then applied in experiments with the state-of-the-art protein A resin mAb Select PrismA<sup>TM</sup>, running in batch mode on a standard single-column chromatography setup, and using both a purified mAb solution as well as a clarified supernatant. The results show that this simple approach, programming the volumetric flow rate according to either of the explored strategies, can improve the process economics by increasing productivity by up to 12% and resin utilization by up to 9% compared to a constant-flow process, while obtaining a yield higher than 99%. The productivity values were similar to the ones obtained in a multi-column continuous process, and ranged from 0.23 to 0.35 mg/min/mL resin. Additionally, it is shown that a model calibration carried out at constant flow can be applied in the simulation and optimization of flow trajectories. The selected processes were scaled up to pilot scale and simulated to prove that even higher productivity and resin utilization can be achieved at larger scales, and therefore confirm that the trajectories are generalizable across process scales for this resin.</p>}},
  author       = {{Gomis-Fons, Joaquín and Yamanee-Nolin, Mikael and Andersson, Niklas and Nilsson, Bernt}},
  issn         = {{0021-9673}},
  keywords     = {{Chromatography scale-up; Flow programming; Flow trajectory; Monoclonal antibody; Multi-objective optimization; Protein A chromatography}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Chromatography A}},
  title        = {{Optimal loading flow rate trajectory in monoclonal antibody capture chromatography}},
  url          = {{http://dx.doi.org/10.1016/j.chroma.2020.461760}},
  doi          = {{10.1016/j.chroma.2020.461760}},
  volume       = {{1635}},
  year         = {{2021}},
}