DRUG - Industrial Green Chemistry 2013/sympo day3... · DRUG • Cancer ... Solid Oral Suspensions...
Transcript of DRUG - Industrial Green Chemistry 2013/sympo day3... · DRUG • Cancer ... Solid Oral Suspensions...
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Pharmaceutical development
Chemical development
Target
therapeutic
area
CANDIDATE
DRUG
• Cancer, immunology research
• Cardiovascular diseases
• Central nervous system diseases
• Metabolic diseases
• Microbial diseases
• Respiratory and Inflammatory diseases
• Viral diseases
DISCOVERY/PIPELINE
Initialsynthesis,
primary andsecondary
screens
Drug metabolismandpharmacokinetics
Toxicology
Pre-clinical development
PHASE I PHASE II
IND CTX
EXPLORATORY
PHASE III
Regulatory
submission Product
licence
Product launch
Post - launch (PHASE IV)
Pharmaceutical developmentPost-launch line extension
development
FULL DEVELOPMENT POST-REGISTRATION
DEVELOPMENT
The Drug Development Process
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5
7
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PRIMARY MANUFACTURING
3
2
41. Batching
2. Charging
3. Reaction
4. Separation
5. Filtration
6. Drying
7. Off-Loading
RESEARCH AND DEVELOPMENT
Inhaled
Solid Oral
Suspensions
Solution
Tablet
sHard Gelatine Capsules
Oral suspensions
Injectables / Topical
sSprays / Nasal sprays,Soft Gelatine Capsules
Metered Dose Inhalers
Dry Powder
Inhalers
S
E
C
O
N
D
A
R
Y
P
R
O
C
E
S
S
I
N
G
SECONDARY MANUFACTURING
DOSAGE FORMS
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1. Batching
2. Charging
3. Reaction
4. Separation
5. Filtration
6. Drying
7. Off-Loading
TYPICAL PHARMA PROCESS
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Kg of Waste Generated / Kg of Drug Produced
Solid
Water
Solvent
VOC's
Others
TYPICAL WASTE GENERATION
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TYPICAL WASTE GENERATION
0
200
400
600
800
1000
1200
1985 1990 2000 2005 2010
Value of API
Value of Waste
US$ b
illion
YearWHO estimates from database
of UNIDO, OECD Health
Data, World Development
Indicators
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PRESENCE OF PHARMA INDUSTRIES
World Investment Report, UNCTAD, Geneva
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CURRENT SITUATION
Operation• Batch Processing• Age Old Technology• Catching up with
Technology
Chemistry• Unstable intermediates• Hazardous intermediates• Energetic systems• Green – Red / Red - Green
Engineering• Chemistry to Operation• Process not optimized• Scale-up Challenges
Business• Speed to Market• Highly Risk Averse• Regulatory Challenges• Capital Intensive
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What could be the best
possible approach to
reduce waste?
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CONTINUOUS PROCESSING
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Continuous Mfg of Lam Stg 3-4 Mfg Capacity: 3.5 TPD (1100 TPA)
B2
(New
)CSTR
CSTR
CSTR
Batching
Separator
pH <4.5
pH >6.8
Continuous
DistillationWashing
Extraction
B1 (Retrofitted to PB1 NH)
Crystalliser
4
3500 kg of Lam Stg 4/day
2565 kg/h
3885 kg/h
1297 kg/h
1590 kg/h
2640 kg/h
1328 kg/h
1328 kg/h
1328 kg/h
145 kg/h
300 kg/h
CME
F/D or
Spray Drier
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PERFORMANCE
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Batch
Semi Continuous
Continuous
Capacity (TPA) 100 380 1100
Unit Cost (GBP) 693 470 366
% Unit Cost Reduction
25 48 60
Gain in Profit (Million GBP)
22 170 610
COST BENEFIT FOR LAMIVUDINE
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CONTINUOUS CLAISEN SET-UP
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• Pilot reactor has been run at 650g/hr of crude product (~4mtpy)
Reactor 1 & 2Volume 120mlOutput 3-4 mtpyCost $15k each
Reactor 3Volume ~1mlOutput 3-4 mtpyCost <$50
Phase separator
PILOT RIG FOR PRAGABALIN(Nitroalkene Reaction)
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FOOT PRINT OF PRODUCTION RIG
Partial Skid Layout for Single
Product Continuous Facility Primary
Dose and
Blend
Granulation
Drying
Secondary
Dose
Secondary
Blender
Tablet Press
Coaters
7.5 metres
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0 5 10 15 20 25 30 35
Batch CapEx
Cont. CapEx
Batch OpEx
Cont. OpEx
Cost £m's or £m's/yr
Overall Cost Comparison
CAPEX & OPEX COST BENEFITS
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OPPORTUNITIES
• Significant cost reduction
• Green Chemistry
• Higher efficiencies / conversions
• Dedicated Plants – Better Planning
• Product Consistency
• Higher Quality
• Safe Operations
• …………………..
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BARRIERS
• Accidental Discovery vs Systematic Development
• Abundance of required raw materials
• Speed to Market – Make it work!
• Commitment of Environmental Protection
• Regulatory Hurdles – Intermediates
• Stringent Quality Requirements
• Analytical Method Development Challenges
• Technology vs Process Requirement
• Lack of Process Analytical Technologies
• Willingness to do something different…
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Good News…..
…………..Our Future could be More Greener Than Past….
• 7 out of 10 Pharmaceutical Companies have already a semi continuous process in their operation.
• 3 out of 10 Pharmaceutical Companies are working on Continuous Processing
• 1 out of 10 Pharmaceutical Companies are already very close (or have) a first generation continuous manufacturing in place.