The economy of scaling-up a bioreactor by increasing the number of units wa
s investigated with respect to an integrated flowsheet. For the production
of t-PA from animal cells, a base case flowsheet using a single large biore
actor was compared to a multiple bioreactor case. Simulation of the complet
e flowsheets for the two cases showed that a multiple bioreactor approach t
o 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 do
wnstream units compared to the base case, since downstream processing accou
nts for about 80% of the total cost for high value products like t-PA. Prop
er scheduling of the downstream units allowed sharing of the equipment by t
he 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 chromatog
raphy columns to the total equipment purchase cost, on the other hand, decr
eased from 52 to 33%. (C) 2000 Elsevier Science S.A. All rights reserved.