Scale-up of protein purification: downstream processing issues

Large-scale chromatography operations continue to occupy a key position in the overall strategy for the downstream processing and purification of protein products for therapeutic use. Increasing product titres from mammalian cell culture has resulted in a trend to identify ways of improving the economics of product recovery and purification processes. In commercial manufacturing, a requirement exists to increase the scale of the chromatography operations, which are typically developed and optimised in small-scale experiments. This short review discusses the key factors in the chromatography process that need to be considered as the scale of the purification step is increased in order to maintain the purity and integrity of the product purified at smaller scale.