Economics of fed-batch operation: a computer-aided approach

The widely anticipated economic potential of fed-batch operation was quantified for a therapeutic product by flowsheet simulation. A process for production of t-PA from CHO cells based on fed-batch operation was compared to a base process that operates in batch mode. Two cases of fed-batch operation were considered, case A, where the product concentration was assumed to be four times the concentration obtained with base process and case B, where the concentration was eight times. The simulator, Bioprocess Simulator (BPS) from Aspen Technology, reported the final bioreactor volume and the total amount of the continuous feeds added during the fed-batch operation. BPS was also used to simulate the downstream processes. Comparison of the economic performances of the processes revealed that return on investment (ROI) of the base process would increase by 112% by switching to case A fed-batch operation from batch mode. Case B, on the other hand, would result in an increase of 288%. The importance of downstream processing for recovery of high-value products became apparent from this study. A breakdown of equipment purchase cost showed that the contribution from the product recovery section increased from 62% for base case to 77% for case A as the product concentration increased by fed-batch operation. For a fixed recovery of 40%, contribution from the downstream section was found to decrease to 70% for case B compared to case A. It was concluded from the results that higher product concentration would not result in proportionate increase in ROI because of limitations in the recovery section. A sensitivity analysis was carried out on several uncertainties of the simulated fed-batch process.