(167b) Cycle to Cycle Control for Continuous Chromatography (MCSGP): Experimental Results for Protein Purifications

Ströhlein, G., ChromaCon AG
Krättli, M., ETH Zurich
Aumann, L., ChromaCon AG
Müller-Späth, T., ETH Zürich
Morbidelli, M., Institute of Chemical and Bioengineering, ETH Zurich

Cycle to cycle control for continuous chromatography (MCSGP): experimental results for protein purifications

Guido Ströhlein1,2, Martin Krättli2, Lars Aumann1,2, Thomas Müller-Späth1,2,
Massimo Morbidelli2

1 ChromaCon AG, Technoparkstr. 1, CH-8005 Zurich, Switzerland

2 Institute of Chemical and Bioengineering, Department of Chemistry and Applied Bioscience, ETH Zurich, CH-8093 Zurich, Switzerland


Continuous chromatography based on the multicolumn countercurrent solvent gradient purification (MCSGP) technology has the potential to purify proteins with high yield and purity, e. g. in the field of monoclonal antibody (mAb) purification [1] and mAb variant separation [2] using preparative ion exchange chromatography. In order to reduce the number of preliminary experiments for process design and to increase the robustness of the MCSGP process against disturbances during operation, a control concept was developed. Recently, a cycle to cycle control concept for simulated moving bed chromatography (SMB) based on analytical HPLC measurements of the product streams was elaborated [3]. In this work a control concept for MCSGP was developed and verified experimentally using only online UV measurements obtained throughout the cycle at each column outlet. The UV signal of all columns is averaged and used as feedback for the controller. According to this, an optimized cycle time is determined. Advantages and disadvantages evolving from this control concept will be discussed and compared to other approaches. For a protein purification, a procedure will be shown how to design and control the MCSGP process from a single overloaded batch chromatography experiment.

[1]        Aumann, Morbidelli, ”A semicontinuous 3-column countercurrent solvent gradient purification (MCSGP) process”, Biotechnology and Bioengineering 2008; 99(3): 728 - 732

[2]        Müller-Späth, et al., “Chromatographic separation of three monoclonal antibody variants using multicolumn countercurrent solvent gradient purification (MCSGP)“, Biotechnology and Bioengineering 2008; 100(6): 1166 - 1177

[3]        Langel, et al., “Implementation of an automated on-line high-performance liquid chromatography monitoring system for ‘cycle to cycle’ control of simulated moving beds”, Journal of Chromatography A 2009; 1216(50): 8806 – 8815