Simulated Moving Bed Technologies for Producing High Purity Biochemicals and Pharmaceuticals

Abstract

Adsorption and Simulated Moving Bed (SMB) processes can be used to purify many chemicals, biochemicals, and pharmaceuticals. SMB processes usually have significantly higher yield, higher throughput, and lower eluent consumption than batch chromatography. Conventional SMB systems have been developed for binary separations. Many major products, however, need to be purified from complex multicomponent mixtures. We have developed comprehensive new technologies for multicomponent separation, which include design methods, versatile SMB equipment, and software tools for process design, simulation, and optimization. The technologies have been tested for the separation of various biochemicals and pharmaceuticals, and are expected to reduce significantly the cost of SMB process development and purification. This article introduces the fundamental principles of SMB and investigates the splitting strategies and design method for multicomponent separations. Insulin purification from a ternary mixture is used as an example. Rate model simulations show that the standing wave design can ensure high purity and yield for all splitting strategies. The simulations also show that mass transfer effects must be considered in SMB design to meet purity requirements and achieve high yields. A decoupled regeneration strategy is developed to avoid gel fouling, and a long-term SMB experiment proves that the SMB process with decoupled regeneration for insulin purification is stable.