Adequate oxygen transfer is a critical parameter in the successful operation of a bioreactor for cell growth and protein synthesis. The volumetric mass transfer coefficient (kLa) of oxygen should be considered during scale-up and scale-down of a process to ensure that the culture can be sufficiently oxygenated and that controlled process changes that impact kLa, such as agitation and gas sparge rate, are scalable. Here, a response surface design was used to characterize the kLa of oxygen at multiple scales of bioreactors, including a 5L glass vessel and single-use Xcellerex XDR bioreactors from 10L to 1000L. Multiple parameters, including agitation, gas sparge and overlay flow rates, direction of pumping, and sparge type, were tested. Calculated kLa values were used to fit a least-squares model in JMP as well as the widely used van’t Riet correlation. The JMP method of statistical analysis provided a closer fit to the measured data compared to the established van’t Riet equation. The analysis is used to evaluate the effectiveness of various bench scale systems as scale-down models, and to aid in optimization of scale-down conditions. Interestingly, under certain run conditions, data suggests that the 5L glass vessels may provide a better model for scale-down of large Xcellerex tanks than the 10L Xcellerex.

Characterizing oxygen kLa in bioreactors to support scale-up and scale-down of cell culture bioprocesses

251st National Meeting (2016)

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