Strategies to Control Batch Integrity in SizeExclusion Simulated Moving Bed Chromatography

In pharmaceutical production, it is important to link each batch of product to its source materials and track each batch throughout the production process. Tracking and controlling each batch is more challenging in a simulated moving bed (SMB) process than in conventional batch chromatography. Solutes coming from a certain feed batch in an SMB can be mixed with solutes coming from adjacent feed batches. The mixing is due to the location of the product ports relative to the feed port, periodic port movement, internal recycle, and dispersion due to mass transfer resistances. The degree of mixing, or the size of the overlap region of the different batches in the product stream, largely depends on solute residence time. Decreasing the zone lengths, 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 (or achieve complete control of batch integrity), an eluent gap can be applied between two 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 closing the feed port during the gap period and opening the feed port only during the feed loading period.