Applications of Simulated Moving Bed chromatography for continuous purification of small and large molecules

Importance of the topic

Continuous purification techniques play a critical role in modern analytical chemistry and industrial processing. Simulated Moving Bed (SMB) chromatography offers significant advantages in terms of productivity, solvent consumption and overall process efficiency compared to traditional batch methods. Its application spans from fine chemical production to biotherapeutic manufacturing, providing high‐purity separations for both small and large molecules.

Aims and study overview

This work illustrates the versatility of the KNAUER AZURA® SMB systems through two representative case studies: the continuous separation of xylitol (a small sugar alcohol) from a fermentation mash and the capture‐mode purification of proteins (immunoglobulin G antibodies) using a multi‐column approach. The goal is to demonstrate process flexibility, scalability and the benefits of continuous operation.

Methodology and instrumentation

The separation of xylitol was carried out in an eight‐column open‐loop SMB configuration. A fed‐batch culture of Candida yeast converted xylose to xylitol, and the resulting mash was analyzed by HPLC. Polymer‐based Eurokat Ca columns, optimized for sugar separations, were used together with water as eluent. Process parameters (flow rates, cycle times, zone configurations) were established via preliminary analytical runs and then implemented in the continuous SMB sequence.

For protein purification, the AZURA® SMB system was operated in Multi‐Column Capture Process (MCCP) mode. The system’s modular design allowed dynamic allocation of columns for binding, washing, elution and regeneration steps. Integrated detectors provided real‐time monitoring and control of the antibody capture cycle.

Instrumentation

• KNAUER AZURA® SMB Lab system with eight columns and programmable pump modules
• Polymer‐based Eurokat Ca columns for sugar separation
• HPLC detectors for feed and fraction analysis
• MCC software for process control and mode switching

Main results and discussion

Xylitol separation achieved 1.8 g purified product per hour with 99 % purity and complete recovery. Analytical chromatograms confirmed clear separation between extract and raffinate streams. In the protein capture mode, continuous operation reduced cycle times and solvent usage while maintaining high antibody yield and purity. The modular SMB configuration delivered consistent fractions and allowed seamless switching between open‐loop SMB and MCCP modes.

Benefits and practical applications

• Enhanced productivity by utilizing the entire column bed continuously
• Reduced solvent and packing material consumption compared to batch processes
• Flexible configuration adapts to diverse separation challenges
• Scalable from laboratory to pilot and production scale in pharmaceutical, food and biotechnology industries

Future trends and applications

Advancements in inline analytics, automated process control and hybrid chromatography formats are expected to further improve SMB performance. Integration with continuous upstream bioprocessing platforms and development of tailored stationary phases will expand applications to complex biomolecules and novel small‐molecule targets. Digital twins and machine learning algorithms may optimize cycle parameters in real time for enhanced resource efficiency.

Conclusion

Simulated Moving Bed chromatography using the KNAUER AZURA® platform enables continuous, high-efficiency purification of both small and large molecules. Its modular design and versatile operation modes deliver significant benefits in productivity, solvent use and process control, making it a valuable technology for industries requiring high‐purity separations.

References

1. KNAUER Application VFD0157: Continuous SMB purification of xylitol from fermentation mash