Optimal loading flow rate trajectory in monoclonal antibody capture chromatography

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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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Externa organisationer
  • KTH Royal Institute of Technology

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kemiska processer


TidskriftJournal of Chromatography A
StatusPublished - 2021
Peer review utfördJa