Small Molecule Chromatographic Purification in Pharmaceutical R&D and Manufacturing

Preparative chromatography has been an integral component of pharmaceutical discovery and development for the past fifty plus years. The past thirty-five years have seen great advances in small molecule purification. Purification techniques have advanced from those centered around large irregular particles operating under low pressure to more efficient high-performance technologies utilizing small spherical particles. Technologies now routinely used include preparative HPLC, SMB, and SFC. At the discovery scale, these advances allow routine and rapid chiral and achiral purification of the large numbers of molecules synthesized at this stage of pharmaceutical R&D. For pharmaceutical development these advances allow chromatographic purifications using HPLC and SMB to be a standard tool in the process development toolbox. The large number of pharmaceutical chiral SMB operations at the manufacturing scale has shown that chromatography can be a cost-effective alternative to asymmetric synthesis or other resolution techniques.

This presentation will discuss the critical role small molecule purification plays within a pharmaceutical company. Multiple real-life examples from ug to metric ton scale supporting Discovery through Manufacturing activities will be presented. In addition, the importance of personnel, facility, automation, and information systems for a successfully integrated purification platform will be discussed.

Presenter: Larry Miller (Associate Director, Novartis)

Larry Miller is an Associate Director in the Global Discovery Chemistry Group at Novartis in Cambridge, MA responsible for analytical and purification support for Discovery. He has spent his career performing small molecule achiral and chiral purifications at the mg to multi-kg scale using a variety of chromatographic techniques. Larry has over 40 peer-reviewed publications and over 45 presentations at scientific meetings. He also co-authored “Modern Supercritical Fluid Chromatography: Carbon Dioxide Containing Mobile Phases” with David Pinkston and Larry Taylor. Larry also serves as co-instructor for an SFC short course which has been held at numerous chromatography conferences in the United States, Europe, and Asia over the past fifteen years. In addition, Larry is the current president of the Green Chemistry Group, a not-for-profit group that organizes the annual SFC conference.