Studying and Simulating the Separation Process of the Production Unit of Tissue Plasminogen Activator

Tissue plasminogen activator is a recombinant protein for treatment. The main industrial production process of this tissue plasminogen activator mainly includes laboratory growth, fermentation, and separation. This study examines the equipment used in separation process, namely centrifuge, ultrafilter, microfilter, chromatography column, ER column, bottler, freeze dryer and mixing tanks, and the unit operations of this section. Retrofitting such as process debottlenecking (time debottlenecking of freeze dryer) and parallelization of the operations for each batch (1.6 kg product) was carried out and the minimum production time was reduced from 12 to less than 7 days and 23 hours for each batch. A storage tank was also installed to prevent the unit shutdown during the freeze-drying failure. The economic analysis shows the share of the direct costs including raw materials, utilities, etc. is 61.73% per batch and the share of indirect costs including lab charges, marketing, research and development, etc. is 38.27%. Arginine includes 97% of the total $247,000 of raw materials costs. Costs of investment, purchase, equipment installation and essentials needed are estimated to be $39,000,000. This cost is mainly for bottling and freeze-dryer systems.