Continuous preparative liquid chromatography in the downstream processing of biotechnological products

Continuous counter-current chromatographic processes have been successfully used in the petrochemical and sugar industry over the last 30 years. Only recently has simulated moving bed (SMB)-technology attracted widespread int erest in the pharmaceutical industry, mainly as a very efficient system for chromatographic enantioseparation. The application of this technique to th e downstream processing of biotechnological products requires some specific changes to meet the special demands of bioproduct isolation. Production pr ocesses are set up on an multi-ton scale, for example, for the purification of fructose with both yield and purity higher than 90%. Examples for other mono- and oligosaccharides are reported. In the purification of fatty acid s or fat soluble vitamins, SMB technology under supercritical fluid conditi ons gives additional benefits and increases the productivity by a factor of four when a pressure gradient is applied. Another field of operation is th e isolation of drug compounds from natural sources where different batch- a nd SMB-chromatographic steps could be successfully combined. First examples are reported for cyclosporine A and paclitaxel isolation. Finally, step-gr adient elution modes can be used continuously, as demonstrated for the isol ation of monoclonal antibodies.