SMB Takes On Paclitaxel Purification

This quick, one-time registration gives you access to members-only site benefits. By Paul A. Metz, Bioxel Pharma, Inc., and Olivier Dapremont, Aerojet Fine Chemicals LLC Simulated Moving Bed (SMB) chromatography is an important technology for separating chiral compounds, but it can also be used in challenging purifications to remove impurities that are structurally similar to target compounds. Bioxel Pharma, Inc. has developed and implemented a fully automated, high throughput SMB process to remove cephalomannine from paclitaxel, an active pharmaceutical ingredient used in cancer drugs. The novel purification process has been running for six months at the FDA inspected site of Aerojet Fine Chemicals in Rancho Cordova, Calif. Paclitaxel and cephalomannine are both natural products isolated from the Canada yew. Removing cephalomannine from paclitaxel is particularly challenging, since the molecular structures of the two compounds are very similar. The overall process, from starting biomass to finished product, is outlined in Figure 1. Bioxel has been producing paclitaxel since 1998 using single-column batch chromatography to remove cephalomannine. However, as demand for paclitaxel increased, the company sought to increase its production scale. While single-column chromatography was selective and produced a high purity product, it lacked the capacity, throughput and yield to meet growing demands. To improve its paclitaxel output and production economics, Bioxel recently installed an SMB purification process, using equipment built by Groupe NovaSep (Pompey, France). The process has been fully validated following the ICH Q7A cGMP guidance for active pharmaceutical ingredients. The facility now running at Aerojet Fine Chemicals can produce up to 120 kg/yr of USP-grade cGMP paclitaxel. U.S., Canadian and European Drug Master Files have been obtained for the new process. The large-scale separation of paclitaxel from cephalomannine poses several challenges, involving tradeoffs in equipment costs, separation efficiency, capacity, product yield and throughput. In addition, because paclitaxel is a