Ester Hydrolysis Reactor

1. Ester Hydrolysis Reactor Emily Brennan Justin Hewitt Fiona Rask

2. Purpose of Unit • Takes output from anion exchanger • Converts insulin ester into pure insulin • Output to HPLC for final purification steps

3. Hydrolysis Reaction • Cleaves a methyl group from insulin precursor using acid catalyst (HCl) • Allows folding into active conformation

4. Neutralization Reaction • Residual sodium hydroxide from anion exchanger is neutralized • Use hydrochloric acid NaOH + HCl  H2O + NaCl

5. Reactor Selection • Continuous reactor selected • Operated in lots to ensure quality assurance requirements are met • Higher productivity than batch • Smaller volume required for same conversion VS

6. Reactor Configuration • 3 reactors in parallel • One reactor running continually to process an upstream lot • Other reactors cleaned/maintained during operation

7. Design Assumptions • 96% reaction extent for hydrolysis • 100% reaction extent for neutralization • Operation time: 330 days/year • Production of insulin crystal: 4065 kg/year

8. Design Specifications • Acid inlet: 15.8 L/h • Upstream process inlet: 19.7 L/h • Residence time estimate: 2 hours • Volume required: 71 L • Volume with 10% head space: 80 L • Well mixed reactor • Material: Stainless Steel

9. Additional Process Considerations • Product sensitive to reactor conditions • Reaction is exothermic and high temperatures can denature insulin • HCl input into reactor and pH extremes can also denature insulin

10. Control Schemes T set point = 40oC

11. Cost Estimate • Reactor Suppliers: • Perry Videx • Walker Engineered Products • New Brunswick Scientific • Controller supplier: • Aspen Technology Inc.

12. Cost of Process • Capital Cost: $ 240,000 • Reactors (3) • Controllers • Operating Cost: $4000/yr • HCl ($72 per ton) • Utilities ($0.06 per kWh)

13. Thank you