wec meeting hamburg, april 14 – 15, 2005 presented by: ludwig metz, bristol-myers squibb cleaner...
TRANSCRIPT
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WEC MeetingHamburg, April 14 – 15, 2005Presented by: Ludwig Metz, Bristol-Myers Squibb
Cleaner ProductionCleaner ProductionDownstream Expectations and Industry Downstream Expectations and Industry
Case StudiesCase Studies
Green Chemistry at Bristol-Myers Squibb Green Chemistry at Bristol-Myers Squibb
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Content of PresentationContent of Presentation
• BMS Green Chemistry
• BMS Taxol Story
• Sustainable Product Design
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Design for Environmental Health and
Safety through GREEN CHEMISTRY
Green ChemistryGreen Chemistry
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What does Green Chemistry Mean?What does Green Chemistry Mean?
• Choosing a non-regulated solvent?
• All aqueous processing?
• Outsource intermediates or products (N.I.M.B.Y.)?
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What is “What is “Green ChemistryGreen Chemistry””
Green Chemistry is reducing or eliminating
the use or generation of hazardous substances - including feedstocks, reagents, solvents, products and
byproducts - from a chemical process.
The Presidential Green Chemistry ChallengeThe Presidential Green Chemistry Challenge
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The Presidential Green Chemistry ChallengeThe Presidential Green Chemistry Challenge
March 16, 1995: President Clinton announced the Presidential Green Chemistry Challenge
• Part of the reinventing Environmental Regulations Initiative to “promote pollution prevention and industrial ecology …”
• Voluntary partnership with Environmental Protection Agency (EPA), trade associations, scientific organizations, academia and the chemical industry
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Sustainable DevelopmentSustainable Development
• Marriage of Green Building Designs with Green Process Designs
• Increasing value to shareholders and the community, while reducing the environmental footprint
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• Safer Chemistry • Employee Exposure Reduction• Reduce use of Target Chemicals• Waste Reduction• Minimize new Regulatory Impact• Support BMS Sustainability Goals 2010• Cost Reduction/Avoidance
Green Chemistry:Green Chemistry:Design for EHS BenefitsDesign for EHS Benefits
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A driver for sustainable development
GREENCHEMISTRY
PRODUCTLIFE CYCLE
POLLUTION PREVENTION
PROCESSSAFETY MNGT
COMPLIANCE
Green ChemistryGreen Chemistry
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2004 Presidential Green 2004 Presidential Green Chemistry Challenge AwardChemistry Challenge Award
TAXOL GREENNESS PROJECT
From U.S. Environmental Protection Agency
Taxol StoryTaxol Story
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TaxolTaxol®®
Paclitaxel
Approved for treatment of ovarian, breast, non-small cell lung cancer, and AIDS-related Kaposi’s sarcoma
in over 50 countries
O
OAcHO OBzH
OHOAc O
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Taxol Early DevelopmentTaxol Early Development
Extract of the bark of the Pacific yew tree (Taxus brevifolia) shows anti-tumor activity (Wall, Wani)
Paclitaxel isolated and identified (Wall, Wani)
Paclitaxel shown to prevent cell division by promoting disassembly of microtubules (Horowitz)
Phase I clinical trials begin
Bristol-Myers Squibb selected by NCI as commercial partner in developing Taxol
1963 -
1971 -
1979 -
1983 -
1991 -
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Taxol Supply IssuesTaxol Supply Issues
• Yew bark contains only ~0.0004% taxol
• Yew trees killed during harvesting
• Pacific yew trees provide the habitat of the endangered spotted owl
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Semisynthetic TaxolSemisynthetic Taxol
• Leaves and twigs are a source of 10-deacetylbaccatin III (10-DAB)
• Biomass contains ~0.1% 10-DAB
• Renewable source cultivated throughout Europe
European Yew TreeEuropean Yew Tree((Taxus baccataTaxus baccata))
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Plant Cell Fermentation (PCF) Plant Cell Fermentation (PCF) TaxolTaxol
Callus derived from needles of the
Chinese yew tree (Taxus chinensis)
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Production cell bank
Seed build-up in liquid culture
Fermentation I: Growth phase
Fermentation II: Production phase
Plant Cell Fermentation and Plant Cell Fermentation and Extraction ProcessExtraction Process
Callus growth on solid agar plate
Whole broth extraction
Chromatographic purification
Crystallization
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Sustainability of SupplySustainability of Supply
• PCF is a reliable year-round source of Taxol
• Yield is not susceptible to the influence of weather conditions, pests and diseases
• PCF Taxol production is faster than cultivation of biomass
• PCF Taxol production levels can be matched to commercial demand
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Waste ReductionWaste Reduction
PCF Taxol production eliminated:
• ~ 240 MT per annum of biomass waste from 10-DAB production
• ~ 6.4 MT per annum of reagents classified as hazardous materials
• 9 different solvents, greatly simplifying composition of waste streams and improving recycle potential
• ~ 350 kg per annum of solid waste
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Other Environmental BenefitsOther Environmental Benefits
Reduced Occupational Exposure
• Eliminated 6 solid-handling steps
• Eliminated handling of 24 reagents classified as hazardous reagents
Reduced Energy Usage
• Eliminated 2 steps that utilize cryogenic temperatures
• Eliminated 6 drying steps
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Business Imperative for Business Imperative for SustainabilitySustainability
• Green Chemistry Program
• Sustainability 2010 goals
• Compliance with all local, state and federal environmental regulations
All factors aligned with Bristol-Myers Squibb’s
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Other Business FactorsOther Business Factors
Product Quality• PCF conditions are more easily controlled to
ensure consistent production of high quality Taxol
Cost of Goods• Process comparison
• PCF has potential for further reductions through development of more productive Taxus cell lines
Natural Semi-Synthetic
PCF
32%20%
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AcknowledgementsAcknowledgements
Technical Operations
- Chemical Development
- Chemical Development Analytical Services
- Manufacturing
Process R&D, Pharmaceutical Research Institute
Environmental Health and Safety
Quality Assurance and Compliance
Business Development
Legal Affairs
Global Regulatory Sciences
Phyton, Inc.
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Sustainable Product DesignSustainable Product Design
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Costs
Environment
Product
ionIntelligence
Effect
Sustainable Health Products Sustainable Health Products 20502050
Requirements of Pharmaceuticals
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Sustainable Health Products and Sustainable Health Products and Service Solutions 2050Service Solutions 2050
Questions and Answers