Development of a scaled-down aerobic fermentation model for scale-up in recombinant protein vaccine manufacturing.

Abstract A simple approach to the development of an aerobic scaled-down fermentation model is presented to obtain more consistent process performance during the scale-up of recombinant protein manufacture. Using a constant volumetric oxygen mass transfer coefficient ( k L a ) for the criterion of a scale-down process, the scaled-down model can be “tuned” to match the k L a of any larger-scale target by varying the impeller rotational speed. This approach is demonstrated for a protein vaccine candidate expressed in recombinant Escherichia coli , where process performance is shown to be consistent among 2-L, 20-L, and 200-L scales. An empirical correlation for k L a has also been employed to extrapolate to larger manufacturing scales.