(605a) Computation Fluid Dynamics (CFD) Guided Design of Single Use Bioreactors (SUBs) at Bench Scale | AIChE

(605a) Computation Fluid Dynamics (CFD) Guided Design of Single Use Bioreactors (SUBs) at Bench Scale


Tran, W. - Presenter, Merck & Co., Inc.
As single-use bioreactors (SUBs) become more prevalent in mammalian cell culture manufacturing, more robust equipment characterization and predictive scaling correlations are needed for better process understanding, scale-up, and technology transfers. During development of new bioreactor designs, modeling and characterization efforts occur in parallel to inform decisions. Over several iterations of design improvement, we found that small physical modifications can add up to incremental impacts on fluid behavior, making previous empirical correlations outdated. This is especially at bench scale and below; slight adjustments in physical structure due to product customization can impact overall power number and mixing.

In this study, we investigated a cell line specific sensitivity to being cultured in a single use vessel compared to similar glass bioreactor designs. Impacts on cell culture performance can be masked by variation from several sources, with the largest factor being inoculum source. It was hypothesized that minor deviations within tight manufacturing tolerances, especially at the bearings of bottom-mounted rotating assemblies, can result in higher strain rates through narrow gaps. Using Computational Fluid Dynamics (CFD) modeling, we discovered unexpected impacts to fluid flow behavior from adjustments such as baffle placement, baffle length, and the curvature of support structures for rotating parts.