Effect of Manufacturability Considerations In Facilitating Efficient Development and Transfer of An Escherichia Coli Process Producing Fc-Fusion Proteins

A commercial fermentation process that produces Fc-fusion proteins as inclusion bodies in E. coli was successfully developed from a clinical process. Various obstacles were encountered as the process performance was further improved. For example, a substantial improvement in titer led to higher oxygen usage and heat removal requirement, which posed a challenge on manufacturing equipment. Subsequently, changes in the fermentation process led to changes in the harvest product profile creating challenges for downstream development. In the end, such obstacles were successfully resolved. Early consideration of manufacturability coupled with clear understanding of equipment design, process parameters and interactions between unit operations were key for an efficient and rapid development of the fermentation process.