wec meeting hamburg, april 14 – 15, 2005 presented by: ludwig metz, bristol-myers squibb cleaner...
TRANSCRIPT
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
Content of PresentationContent of Presentation
• BMS Green Chemistry
• BMS Taxol Story
• Sustainable Product Design
Design for Environmental Health and
Safety through GREEN CHEMISTRY
Green ChemistryGreen Chemistry
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.)?
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
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
Sustainable DevelopmentSustainable Development
• Marriage of Green Building Designs with Green Process Designs
• Increasing value to shareholders and the community, while reducing the environmental footprint
• 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
A driver for sustainable development
GREENCHEMISTRY
PRODUCTLIFE CYCLE
POLLUTION PREVENTION
PROCESSSAFETY MNGT
COMPLIANCE
Green ChemistryGreen Chemistry
2004 Presidential Green 2004 Presidential Green Chemistry Challenge AwardChemistry Challenge Award
TAXOL GREENNESS PROJECT
From U.S. Environmental Protection Agency
Taxol StoryTaxol Story
TaxolTaxol®®
Paclitaxel
Approved for treatment of ovarian, breast, non-small cell lung cancer, and AIDS-related Kaposi’s sarcoma
in over 50 countries
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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 -
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
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))
Plant Cell Fermentation (PCF) Plant Cell Fermentation (PCF) TaxolTaxol
Callus derived from needles of the
Chinese yew tree (Taxus chinensis)
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
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
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
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
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
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%
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.
Sustainable Product DesignSustainable Product Design
Costs
Environment
Product
ionIntelligence
Effect
Sustainable Health Products Sustainable Health Products 20502050
Requirements of Pharmaceuticals
Sustainable Health Products and Sustainable Health Products and Service Solutions 2050Service Solutions 2050
Questions and Answers