Single versus multiple bioreactor scale-up: economy for high-value products

The economy of scaling-up a bioreactor by increasing the number of units was investigated with respect to an integrated flowsheet. For the production of t-PA from animal cells, a base case flowsheet using a single large bioreactor was compared to a multiple bioreactor case. Simulation of the complete flowsheets for the two cases showed that a multiple bioreactor approach to scale-up increases the return of investment (ROI) of the base process by 122%. This enormous increase in ROI results from the smaller size of the downstream units compared to the base case, since downstream processing accounts for about 80% of the total cost for high value products like t-PA. Proper scheduling of the downstream units allowed sharing of the equipment by the bioreactors. A breakdown of the equipment purchase cost showed that cost related to cell culture equipment increased from 14% for the base case to about 37% for the multiple bioreactor case. The contribution from chromatography columns to the total equipment purchase cost, on the other hand, decreased from 52 to 33%. (C) 2000 Elsevier Science S.A. All rights reserved.