Scale-Up of Microbial Fermentation Process

This chapter covers a broad scope of issues related to microbial fermentation process scale-up and describes specific steps to plan and execute a scale-up project. The purpose of a seed train is to propagate cells to a desired mass for inoculation into the production bioreactor. The traditional seed train includes thawing a vial and inoculating into shaker flasks for a certain number of stages with increasing flask sizes, and may include stainless steel reactors. The essence of scale-up of a fermentation process is to demonstrate fermentation production at large scale resulting in the same productivity and quality as that developed at small scale. A section of the chapter discusses specifically the scale-up of the bioreactor operational parameters such as agitation, airflow rate, and cooling capability based on small-scale data. At large scale, large amounts of bulk raw materials are expected. Their transportation, delivery, handling, and storage are to be considered and planned prior to scale-up. Scale-up projects often require implementation of new equipment or modification of existing equipment. A unique requirement for commercial biopharmaceutical process scale-up is process validation. With the tremendous diversity of organisms and products in industrial fermentation, a precise and one-size-fits-all strategy for scale-up is not practical. The keys for scale-up are to achieve project goals, produce desired product with acceptable quality and yield, and fully understand and control operational risks at large-scale manufacturing.