Simulated Moving Bed Chromatography (SMBC) current status and applications for protein purification

Most of the biopharmaceuticals produced by recombinant DNA technology requires efficient high throughput purification techniques and process strategies for their production in a cost-competitive manner. Purification of proteins is often considered as most challenging area compared to small molecules because of their large molecular weight, maintenance of the conformational structure and biological activity to meet the stringent regulatory issues. As a versatile tool, liquid chromatography has become an inevitable part of protein separation and analysis processes. It is expected that continuous counter-current chromatography concepts based Simulated Moving Bed Chromatography (SMBC) processes might offer distinct advantages over batch chromatographic processes e.g. high throughput, improved productivity, reduced solvent consumptions and higher product concentrations. Determination of adsorption isotherms, modeling, simulation and proper design of the separation process are the key issues involved in the SMBC processes. Dimensionless liquid flow rate ratio among the different sections of SMBC and switch time (corresponding to the stationary phase flow rate) plays an important role in the separation of components. In the last few years, SMBC has started finding its applications in the continuous protein purification beyond its well known applications in petrochemicals, chiral chemicals and sugar industries. There are already reports on the affinity, size-exclusion and ion exchange chromatography based SMBC processes for the purification of proteins. There are various modifications in the classical 4 zone SMB chromatography processes to meet the process requirements e.g. Reduction in the zones, varying the feed concentrations. Current state of the SMB technology, potential and industrial relevance for its applications in multi-component separation will be presented in detail