1. Bristol-Myers Squibb:Compound for the Treatment of Hepatitis C
Danielle Adams, Paige Brown, Andreas Buehlmann, Cristina Chiacchiero, Brittany Jewett, Jovanna Manzari, Lauren McTigue
ChE 345
Process Control, Modeling, & Simulation
Professor Podkolzin
Tuesday, May 2, 2017

2. Presentation Outline Introduction to Project Control Objectives
Relevant Variables
Process Description and Diagram
Process Simulation
Control Strategy
Safety Measures
Conclusion

3. Introduction to the Project
Patent US B2 issued for the process of synthesising a compound for the treatment of hepatitis C
One strand of HCV RNA genome consists of 9500 nucleotides and encodes one polyprotein consisting of 3000 amino acid
In cells affected by HCV this polyprotein is cleaved at multiple sites to produce structural and non-structural (NS) proteins
This invention provides technical advantages as well as pharmaceutical advantages with regard to mechanisms of action, binding, inhibition efficiency, target selectivity, solubility, safety profiles, or bio-availability

4. Control Objectives
Gently heat the initial mixture to 40 degrees Celsius and keep the temperature constant for 12 hours
Cool the mixture to 0 degrees Celsius with the addition of HCl

5. Variables Control Variables Temperature of the initial mixture
Final temperature of the mixture after cooling
Manipulated Variables
Flow rate of steam used to heat the mixture
Flow rate of water used to cool the mixture
Disturbance Variable
Change in surrounding air temperature due to human error

6. Process Outline Description and Diagram

7. Control Strategies PID Controller Steam Valve Water Valve
Temperature sensor
Thermocouple
PID Controller
Feedback control
Steam Valve
Fail close
Water Valve
Fail open
•Valve

8. Process Simulation Model

9. Process Simulation Output
Disturbance: Worker leaves door open during heavy snowstorm which causes the mixture to cool down

10. Safety Measures Lab Scale Safety Proper PPE
Following lab safety practices
Safe storage of chemicals and glassware
Manufacturing Scale Safety
Proper PPE
Steam Heated Tank Safety
Feedback Loop for automatic temperature adjustments
Operator Input restrictions
Temperature alarms to indicate feedback loop errors
Fail Open and Fail Close Valves
Emergency Stop Button
Sends Valves to the indicated ‘failure’ settings

11. Conclusion Key Takeaways
Gained understanding of specific control strategies
Feedback vs Feedforward
Fail close vs Fail open
New knowledge about relevant safety measures
Exposure to Patents
Experience working with a large team