1. 1 BMS Confidential PUBD 13745 Using the Rowan University Engineering Clinic Model to Implement Green Engineering Partnerships with the Pharmaceutical Industry C. Stewart Slater, Mariano J. Savelski, Brian G. Lefebvre, Stephanie Farrell, Robert Hesketh Rowan University, Department of Chemical Engineering, Glassboro, NJ The 11th Annual Green Chemistry & Engineering Conference Session: Education and Outreach IV 12 th Green Chemistry & Engineering Conference Washington, DC June 22-26, 2008

2. 2 BMS Confidential PUBD 13745 Academic-Industrial Interaction Projects supported through –Industry - Rowan Engineering Clinics Prgm –US EPA Pollution Prevention Prgm – Reg 2 Three pharmaceutical company partners –Bristol-Myers Squibb –Novartis –Pfizer Process case study or problem has a green chemistry and engineering component “Paper-projects” / design-based and/or experimentally-based B R P N

3. 3 BMS Confidential PUBD 13745 Rowan University Clinics Modeled after medical schools Student-faculty problem solving teams Applied research, development, design Partnership: Industry, Federal/State Agency, Foundation Multidisciplinary Two 3 hour labs/wk, 1 hr/wk meeting with professor/industry Both semesters of Junior & Senior year and Masters students

4. 4 BMS Confidential PUBD 13745 Rowan’s Project Based Curriculum

5. 5 BMS Confidential PUBD 13745 Clinic Timeline Preliminary contact Confidential disclosure / IP agreement Initial meetings: Rowan faculty/students with Process R&D scientists/engineers Clinic partnership agreements Set and review project goals/objectives Review of process documentation Site visit (plant / R&D) Weekly project meetings with student team Students interact as needed with industry partner End of semester presentation to industry partner

6. 6 BMS Confidential PUBD 13745 Partner Contributions Ingredients for a successful project –“Champion” for green engineering and partnering from industry –Dedicated industry and academic mentors –Project matched to faculty and student expertise –Sufficient resources allocated (time and $) –Realistic timelines and expectations –Reasonable confidentiality agreements – presentations/papers –Projects that ‘map’ to programmatic goals/objectives, ABET criteria

7. 7 BMS Confidential PUBD 13745 BMS Project - “Green Drying” of Solvents Integration of pervaporation membrane technology for THF solvent recovery Process step in new oncology drug synthesis Evaluate replacing constant volume distillation (CVD) Review current practices – solvent use and waste Review literature and vendor info for “best practices”

8. 8 BMS Confidential PUBD 13745 Project Results Design analysis –Tracking solvent use –Match to pharmaceutical processing criteria –Integration into pilot plant process –Develop simulation model Batch Processing Multiple Solvents Purity Requirements cGMP Compliant Processing Time

9. 9 BMS Confidential PUBD 13745 Project Results Analysis on pilot-scale production Design analysis –Environmental impacts – LCA –Carbon “footprint” –Economics –Recommend vendors Estimate impacts for scale-up

10. 10 BMS Confidential PUBD 13745 Design an external fixed bed adsorption column for the removal of Pd from pharmaceutical reaction mixtures Increase efficiency of current methods used for Pd removal –Current method requires a lot of time, money, equipment, processing steps, solvent for rinsing Novartis Project: Adsorption Process for Catalyst Reduction

11. 11 BMS Confidential PUBD 13745 Characterize adsorbents –Capacity –Isotherm parameters –Selectivity of resin for Pd. vs. reaction product ($$) Operating conditions for the column –Flow rate –Amount of resin needed –Temperature –Breakthrough curves Is fixed bed adsorption better –Business aspect ($$) Project Results

12. 12 BMS Confidential PUBD 13745 Project Results Developing lab-scale palladium adsorption column –Key operating parameter = residence time in column Column-based adsorption is an improvement over current removal techniques –Time, equipment, solvent use Continue to examine effect of fluid residence time on bed efficiency Model and scale-up for industrial use

13. 13 BMS Confidential PUBD 13745 Pfizer Project: Waste Minimization and Solvent Recovery Investigate solvent recovery alternatives to minimize waste from the Celecoxib manufacturing process Compare current process route with green engineering options –Waste stream reduction and isopropanol (IPA) recovery –Define operational sequences –Equipment and process steps required –Estimate costs and environmental impacts –Make proposal / recommendations

14. 14 BMS Confidential PUBD 13745 Analysis of manufacturing-scale API production –Barceloneta, Puerto Rico plant –Recovery of isopropanol from water, other alcohols and dissolved solids –Multiple waste streams with varying compositions –Azeotropic mixtures add complexity –Design limitations based on equipment available Student team interacts with –Global Manufacturing Services, New York, NY –Global Engineering, Peapack, NJ –Plant operations, Barceloneta, PR Project Results

15. 15 BMS Confidential PUBD 13745 Separation and recovery process feasibility and economic analysis –Distillation –Extractive Distillation –Reactive Distillation –Molecular Sieves –Pervaporation Simulation and design case study approach –Separation sequence – ASPEN and Rowan-developed methods Life cycle assessment of process alternatives –Environmental impact – SimaPro, EcoSolvent Project Results

16. 16 BMS Confidential PUBD 13745 Benefits of Partnership Publicity/community relations Exchange of new green engineering ideas Industry validates approaches to green engineering New engineers graduate with knowledge in green engineering and pharma industry culture University develops expertise to advance state-of-the-art in green engineering

17. 17 BMS Confidential PUBD 13745 Acknowledgements Bristol-Myers Squibb San Kiang Thomas LaPorte Lori Spangler Stephan Taylor Novartis Thomas Blacklock Michael Girgis U.S. EPA Grant NP97257006-0 Pfizer Jorge Belgodere Peter Dunn Greg Hounsell Daniel Pilipauskas Frank Urbanski