276572 Characterizing Heterogeneity of Environmental Conditions in Various Bioreactor Scales Used for Cell Cultivation
Large scale mammalian cell culture up to 20000L is developing more and more to an industrial standard. Process up scaling to those volumes is a fundamental necessity to guarantee process performance, product amount and product quality. Therefore, it is of outmost importance to be aware of scale dependent variables influencing the process. Reactor geometry, shear stress distribution, dissolved O2 and CO2 distribution and gas mass transfer rates can be very different in between scales, resulting in non-desired variations of process performance.
We studied scale dependent parameters (e.g. shear stress, kLa, DO, pCO2, and mixing time) from small to largest scale bioreactors, covering a volume range from 3L up to 15000L, using CFD simulation. At each scale, CFD simulations were validated against relevant scale dependent parameters (e.g. kLa, DO distribution, mixing time) measured experimentally. Comparisons of the computational and experimental values were in good agreement supporting the used approach. Such CFD simulations were consequently used to characterize heterogeneity of the environmental conditions (i.e. shear stress, DO, mixing time etc.) and to understand limitations of actual lab scale bioreactors currently used for process development. We will discuss those limitations and propose more suitable downscale approaches to fit large scale conditions already during process development.
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