(372a) Automation and Control of Continuous Countercurrent Tangential Chromatography

The integration and automation of continuous bioprocesses has drawn significant interest among biopharmaceutical companies in recent years as they offer economic and product quality benefits over traditional batch processes^[1]. Crucial to these bioprocess pipelines are the continuous chromatographic separation methods that have been developed to facilitate product capture and polishing, including periodic countercurrent multi-column chromatography, multi-column countercurrent solvent gradient purification, and continuous countercurrent tangential chromatography (CCTC)^[1,2].

Among these methods, CCTC has addressed many bottlenecks of conventional packed bed chromatography by providing truly continuous steady-state operations with simple controls^[3]. In CCTC, the chromatographic resin slurry flows through a series of static mixers and hollow fiber membrane modules, enabling high yield and purification while reducing buffer requirements^[3,4]. The governing steps include binding, washing, elution, and regeneration. In this study, we develop a mechanistic model of the binding step in CCTC by incorporating intraparticle diffusion, adsorption-desorption kinetics, film mass transfer, and mass conservation in the bulk flow. Monte Carlo simulations are conducted to quantify system uncertainties using parameters from previously published literature. The calibrated model is experimentally validated on continuous operations, and the concentration profiles in the binding step are shown to be accurately predicted by the model. A model-based control strategy is proposed to compensate for system variations coming from feed composition and environmental factors. System optimization studies are included to maximize capture yields. Overall, our modeling and control work for CCTC operation build a framework for automating continuous chromatographic separation.

[1] Subramanian, G. ed., 2017. Continuous biomanufacturing: innovative technologies and methods. John Wiley & Sons.

[2] Zydney, A.L., 2015. Perspectives on integrated continuous bioprocessing—opportunities and challenges. Current Opinion in Chemical Engineering, 10, pp.8-13.

[3] Dutta, A.K., Tan, J., Napadensky, B., Zydney, A.L. and Shinkazh, O., 2016. Performance optimization of continuous countercurrent tangential chromatography for antibody capture. Biotechnology progress, 32(2), pp.430-439.

[4] Dutta, A.K., Tran, T., Napadensky, B., Teella, A., Brookhart, G., Ropp, P.A., Zhang, A.W., Tustian, A.D., Zydney, A.L. and Shinkazh, O., 2015. Purification of monoclonal antibodies from clarified cell culture fluid using Protein A capture continuous countercurrent tangential chromatography. Journal of biotechnology, 213, pp.54-64.