(191ah) CFD Modeling of Bioreactor Mixing Properties

Nelson, M., Merck & Co
Pollard, J., Merck
During scale-up/scale-down of therapeutic protein manufacturing processes, mammalian cell culture bioreactors from tens of milliliters to thousands of liters in size are utilized. Reactor design changes significantly across this large volume range, with aspects like vessel geometry, impeller type and number, and gas sparging setup varying considerably. This often makes mixing and gas transfer behavior difficult to predict, necessitating numerous trial-and-error experiments to choose control parameters like impeller RPM and gas sparge rate. This study investigates the use of Computational Fluid Dynamics (CFD) to model bioreactor behavior at different volume scales.

CFD modeling has the potential to describe bioreactor mixing properties such as mixing time, dissolved gas concentration, and shear stress, over a large operating parameter design space with minimal experimentation. In this presentation, we will present the use of the “ANSYS CFX” CFD solver to compare mixing properties of AMBR250 250-mL microbioreactors and 3-L bench top bioreactors. We will focus on the key scaling properties of power per volume ratio (P/V) and volumetric gas transfer constant (kLa).