Postgraduate Seminar Presentation : Biocatalytic continuous manufacturing of diabetes drug: plantwide process modeling, optimization, environmental and economic analysis

Speaker Ho Chi-Hung (Supervisor: Dr Wang Xiaonan)

Host Department of Chemical and Biomolecular Engineering

Date/Time 20 Nov - 20 Nov, 10.00am

Venue E5-02-32 , Faculty of Engineering, National University of Singapore


This work proposes a comprehensive framework of biocatalytic continuous manufacturing of sitagliptin, the active pharmaceutical ingredient of the leading dipeptidyl peptidase-4 inhibitor antidiabetic drug. Continuous manufacturing has advantages of quality consistency, reduced waste and more cost-effectiveness in comparison to batch manner. Furthermore, compared to traditional catalysts, biocatalysts feature less environmental footprints. An end-to-end flowsheet is designed with reaction rate constant determined according to the published data. Based on the steady-state model of the plug-flow microreactor, the optimized productivity is identified as of 2.6 x 10^(-2) mol hr-1 through surrogate-based optimization. The environmental impact assessment demonstrates its sustainability with a low E-factor of 53 compared to 200 of traditional processes. A cradle-to-gate life cycle assessment indicates most impacts can be attributed to materials and solvents, in which trifluoroacetic anhydride accounts for the majority of impacts. A comprehensive techno-economic analysis has also been performed, validating the economic feasibility of this process line with a Net Present Value of $150 million over a 20-year time. Therefore, this present paper demonstrates the feasibility, sustainability and economic competitiveness of the proposed process.