Development of a Shaken Scale-Down Model: Characterization of Critical Parameters in Bioprocess Development

摘要

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 Shake Flask Reader (SFR) 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. A 2 L scale stirred-tank model for a production process at 1,000 L scale was further scaled down. The developed shaken scale-down model at approx. 0.1 L scale had very simple, manual control of pH and dissolved oxygen concentration, realized by online monitoring of the two parameters with the SFR Shake Flask Reader. Though this control was of much lower quality compared to a fully online controlled stirred-tank bioreactor, similar data for IEC-patterns, glycosylation content, and viable cell density - important quality attributes - could be achieved with the shaken scale-down model. Other process parameters like power input, shear stress and their influence on process performance in the scale-down model will have to be investigated further.