Scale-Up of Protein Purification: Downstream Processing Issues.

Separation science continues to occupy the central position in the overall strategy for the downstream processing and purification of therapeutic protein products for human use. Increasing product titers from mammalian cell culture and new emerging classes of biopharmaceuticals has presented a challenge to the industry to identify ways of improving the robustness and economics of chromatography processes. In commercial manufacturing, there is always a need to increase the scale of the chromatography operations which are typically developed and optimized in small-scale laboratory experiments. This 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.