(586ai) Scale Up of the Chromatographic Process

Scale Up of the Chromatographic Process

Steffen Kidal, Novo Nordisk A/S

The transfer of chromatographic processes from lab. scale to pilot and production scale is an important and challenging task in the pharmaceutical industry, and has been dealt with in several - more or less obvious - ways. Traditionally the process is scaled by increasing the column diameter while keeping the bed height, the velocity, and the volumes of the different phases (measured in column volumes) constant. Our approach was to find a practical flexible and consistent method, a tool, which requires only a few experiments to produce a safe process transfer.

The process transfer is considered as a two-step operation. The first step is the scale up of the column process, which follows the principle of scaling on a volume basis (constant residence time for the proteins). This concept is quite simple and does not involve any new theory. The second step deals with the extra column effects created by instrumentation (dead volumes, mixer characteristics etc.).