Development Of A Shaken Scale-Down Model

A shaken scale-down model at approx. 0.1 L scale for a previously established stirred-tank model at 2 L scale was developed. In the shaken scale-down model online monitoring of pH and dissolved oxygen concentration was performed using the SFR Shake Flask Reader by PreSens. Though only a simple, manual control of these two parameters could be realized the shaken scale-down model achieved similar data to the stirred-tank model for viable cell density, specific glycosylation content, and ion exchange chromatography pattern. These results suggest that for this process the importance of pH and DO control might be overestimated and further investigations have to be made for evaluating and comparing the influence of shear stress and power input in both models.

Scale-down models are used to characterize critical parameters and settings of their proven acceptable range in bioprocess development. This way costs and time can be saved and a reliable scale up can be guaranteed in biotechnological production processes for active pharmaceutical ingredients. An already established 2 L scale-down model for a production process at 1,000 L scale should now be further scaled down to a shake flask with approx. 0.1 L working volume. Differences in flow patterns, power input, oxygen transfer, mixing shear stress, foam formation and so on have to be taken into account when trying to establish this shaken scale-down model to a stirred-tank production process.

By scaling down the stirred-tank process it is possible to increase the number of parallel experiments while reducing the costs. At the same time larger numbers can increase the significance of process characterization studies and a better model quality can be achieved. The SFR Shake Flask Reader by PreSens (Regensburg, Germany) was used in these experiments to monitor pH and dissolved oxygen concentration in the shake flasks. The system applies chemical optical sensors attached to the bottom of the shake flasks, which are read out non-invasively with the SFR inside the incubator.