Methods to Control Batch Integrity in SMB Chromatography for Linear Systems

For a pharmaceutical like insulin, the product should be clearly linked to its source. Therefore, it is important to track each batch throughout the production process. Tracking each batch in a simulated moving bed (SMB) process is more challenging than in conventional batch chromatography. Solutes coming from a certain feed batch in SMB can be mixed with solutes coming from adjacent feed batches as a result of periodic port movement, internal recycle, and dispersion due to mass transfer. The degree of mixing or the size of the overlap region in the product stream largely depends on solute residence time. Using partial feeding, or applying pinched wave operating conditions can effectively reduce residence time and therefore decrease the overlap region. To eliminate the overlap region completely, an eluent gap can be applied between adjacent feed batch injections. The strategies for reducing residence time can minimize the eluent gap, thereby reducing eluent consumption and increasing productivity. One can further reduce the amount of eluent by operating as a three-zone SMB during the gap period and a fourzone SMB during the feed injection period.