Development of a Robust Small-Scale Production Format that Is Predictive of Bioreactor Performance

Small-scale cell culture methods have been widely used to screen multiple cell lines or cell culture conditions prior to confirmation or further evaluation in controlled bioreactors (Betts and Baganz, 2006). However, as the standard industry practice has moved toward longer duration, high cell density fed-batch production modes, the small-scale systems have failed to be a reliable predictor of bioreactor performance. Specifically, cells cultured in multi-well plates or shake flasks are generally unable to match the cell growth observed in bioreactors, often with consequences to product expression, product quality and metabolic responses. Thus, the small-scale models are not a good predictor of performance in bioreactors.