Transcript Document

The 11th Annual Green Chemistry & Engineering Conference
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
Session: Education and Outreach IV
12th Green Chemistry & Engineering Conference
Washington, DC June 22-26, 2008
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Academic-Industrial Interaction
• Projects supported through
– Industry - Rowan Engineering Clinics Prgm
– US EPA Pollution Prevention Prgm – Reg 2
N
P
B
• Three pharmaceutical company partners
– Bristol-Myers Squibb
– Novartis
– Pfizer
R
• Process case study or problem has a green
chemistry and engineering component
• “Paper-projects” / design-based and/or
experimentally-based
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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
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Rowan’s Project Based Curriculum
Industry
Clinics
Courses
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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
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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
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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”
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Project Results
• Design analysis
– Match to
pharmaceutical
processing criteria
– Integration into pilot
plant process
– Develop simulation
model
Solvent Intensity (kg/kg API)
– Tracking solvent use
4500
4228
4000
3500
3000
2500
2000
1500
1000
500
254
197
?
Kilo
Pilot
Manufacturing
0
Discovery
Process Scale
Batch
Processing
Multiple
Solvents
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Processing
Time
Purity
Requirements
cGMP
Compliant
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Project Results
• Analysis on pilot-scale
production
• Design analysis
Emissions
THF
Manufacturing
Emissions
Emissions
– Environmental impacts
– LCA
– Carbon “footprint”
– Economics
– Recommend vendors
Waste
Incineration
API
Manufacture
Raw Materials
Utilities
Emissions
$2,000,000.00
$1,500,000.00
$1,000,000.00
$500,000.00
$
• Estimate impacts for
scale-up
TAS
$0.00
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
NPV
-$500,000.00
-$1,000,000.00
-$1,500,000.00
-$2,000,000.00
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kg API
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Novartis Project: Adsorption Process for
Catalyst Reduction
• 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
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Project Results
20000
60 °C
• Characterize adsorbents
– Capacity
– Isotherm parameters
– Selectivity of resin for Pd. vs. reaction
product ($$)
Solid-phase Pd Concentration, ppm
18000
16000
14000
12000
10000
40 °C
8000
6000
25 °C
4000
2000
0
0
50
100
150
200
250
300
350
400
Liquid-phase Pd Concentration, ppm
• Operating conditions for the column
–
–
–
–
Flow rate
Amount of resin needed
Temperature
Breakthrough curves
• Is fixed bed adsorption better
– Business aspect ($$)
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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
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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
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Project Results
• 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
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Project Results
• Separation and recovery process
feasibility and economic analysis
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–
–
–
–
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
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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
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Acknowledgements
Bristol-Myers Squibb
San Kiang
Thomas LaPorte
Lori Spangler
Stephan Taylor
U.S. EPA
Grant NP97257006-0
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Novartis
Thomas Blacklock
Michael Girgis
Pfizer
Jorge Belgodere
Peter Dunn
Greg Hounsell
Daniel Pilipauskas
Frank Urbanski
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