Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Continuous countercurrent chromatography has been established in industrial operations for over six decades and in fine chemical and pharmaceutical industry since the 1990s. In biotechnological processing, the area where chromatography plays a criticaland often multipleroles, implementation is lacking for various reasons. Options are shown to correct this and make continuous countercurrent chromatography a technologically and economically viable option in GMP-regulated processing. Current approaches, with the exception of MCSGP (multicolumn countercurrent solvent gradient purification), just operate a manifold of 2–6 columns in a sequential but batchwise scheduling. Modifications were made to reduce equipment complexity in GMP-regulated manufacturing and to exploit benefits of countercurrent operation for adsorbent and buffer reduction. A solution with only one column and a minimum of valves, pumps, and buffer vessels was developed. The approach also describes integration of two or more chromatography steps in continuous production, both GMP- and biocompatible.