Conventional wisdom says process chromatography is expensive. It is necessary for biomolecular separations, but should be avoided in small-molecule manufacturing. It is inherently a batch process, usually requiring multiple injections to process a single reactor-load of product, and it consumes vast amounts of solvent and packing material.

Everything conventional wisdom says about process-scale chromatographic separations is wrong—or at least requires a lengthy footnote to explain the exceptions. And high on the list of exceptions is multicolumn continuous chromatography, the category that includes simulated moving bed (SMB) chromatography and its descendants.

The largest multicolumn continuous chromatography unit in service in North America: the 5 x 1000-mm Novasep Process system which went into service in March 2006 at Ampac Fine Chemicals' Rancho Cordova, California facility.

Tortoises and hares

Continuous chromatography links multiple columns—typically five to eight of them—in a loop, outlet to inlet, with additional inlets for raw product feed and two outlets, one for target product (extract) and the other for discarded product (raffinate). To make the process continuous, the feed, extract, and raffinate ports cycle from column to column, lagging behind the solvent flow. The effect is as though the stationary phase were moving backward relative to the feed port, while the solvent is moving forward. If the stationary phase, mobile phase, and flow rate are chosen properly, the viewer straddling the feed port sees the product stream divide into two continuous streams, with one component flowing continuously downstream and the other flowing continuously upstream (Figure 1).