Computer simulation for large scale bioprocess design

Two bioprocess simulators, Aspen BpS(TM) and SuperPro Designer(R), were use d to simulate and compare two flowsheets for production of tissue plasminog en activator (t-PA) from Chinese hamster ovary (CHO) cells. The flowsheets were designed to compare the economics of using serum and serum-free medium in the bioreactor. The base case flowsheet used a medium with 10% serum wh ile the alternative flowsheet used a serum-free medium. Affinity chromatography was the major step in the downstream processing of the base case flowsheet. The alternate flowsheet was designed for two-step cell culture growth and production. Ion-exchange chromatography was conside red sufficient for purification of the low protein medium for this case. At a price of US$ 25/l for serum-free medium, the alternate flowsheet was fou nd to have an return on investment (ROI), of 115% compared to 65% for the b ase case flowsheet. (C) 2001 Elsevier Science B.V. All rights reserved.