The Power to Anticipate Manufacturing Issues

Theory only goes so far in process development. At Ricerca, practical engineering aspects factor strongly in our work to optimize a process. Since we always keep in mind that manufacturing is the client's ultimate goal (even at the early development stages), our clients get a data package useful for developing the commercial process along with the first-time scale-up. Although we anticipate commercial manufacturing issues, we also balance risks and costs to provide appropriate process improvement for the current development stage.

One example: A major drug company asked us to develop the technical information package for a first-time scale-up of an anti-asthmatic drug. Our work involved a ten-step segment of a twenty-step convergent preparation and required an optical isomer resolution. Starting with the medicinal chemistry procedure and with the synthetic route frozen (as the client specified), we were able to significantly improve the process by eliminating nonscaleable steps, an unstable intermediate, and the requirement for cryogenic temperatures. We also upgraded yield and selectivity; obtained intermediates as crystalline solids rather than as oils; and replaced some of the more expensive raw materials. The improved process was successfully demonstrated at the 12-liter scale and as a bonus the client got a kilogram of the material.