Scale-Up of Protein Purification: Downstream Processing Issues.

Large-scale chromatography operations continue to occupy the central position in the overall strategy for downstream processing and purification of therapeutic protein products for human use. As the biopharmaceutical industry looks forward to embracing new therapeutic modalities such as viral vector-mediated gene therapy, it is becoming evident that chromatographic separations will be also be crucial for success in that discipline. The current industry focus on cell culture intensification strategies that can result in increased process efficiency and lower cost of goods is presenting challenges to the robustness and economics of chromatography processes. To ensure robust and reproducible commercial manufacturing strategies, there is always a mandate to increase the scale of chromatography unit operations that are typically developed and optimized in small-scale development trials. This chapter discusses the key factors in typical chromatography operations that need to be carefully considered and modeled during the process scale-up phase in order to maintain the purity, yield, and quality of a product purified at smaller scales.