Flexible Facilities
Economic and Environmental
Impact of Going Disposable
Geoffrey Hodge, Xcellerex
ISPE Clean & Green Seminar
13 April 2009
…speeding medicines to people…
Xcellerex Business Model
Contract Services
Products
PDMax™ process
development
XDR™ bioreactor
GMP Manufacturing
XDM™ mixer
FlexFactory™
FlexFactory
XCELLEREX
Proprietary Drugs
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Opportunity: Market Drivers for
Next Generation Biomanufacturing
• Rapid expansion of markets
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$80+ billion biotherapeutics market
Resurgent vaccine market
Pandemic and bioterror threats
Emerging follow-on / biosimilars market
• Globalization of biotechnology
High efficiency manufacturing expertise is enabling
3
Advantages of Single Use Systems
Reductions in:
• Cleaning
• Sterilization
• Engineering cost
• Equipment lead time
Lead to
• Utility requirements
• Validation
• Quality / Regulatory burden
• Space
• Labor
• Waste generation
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Improvements in:
• Manufacturing quality
• Capital investment
• Facility buildout time
• Cycle time
• Flexibility
• Environmental impact
• COGS
™
The XDR : Single Use GMP Bioreactor
(200L, 500L, 1000L & 2000L working volumes — XDR-200 Shown)
Exhaust filter heater
Bag pressure protection and ΔP weight control
Disposable Bag Assembly (incl.
PLC or Delta V Controller:
Filters & Tubing)
pH, DO, agit., temp, gas
sparge, CO2 strip,
Jacketed Stainless Steel
headspace gas, weight,
Support Tank
media feed
View Ports
Integrated Acid/Base, Media
Probe Ports
Feed Pumps
Tank weight control
- Δ P or load cells
Temperature Control Unit
-cooling and heating – no
Shaftless, Seal-less
Bottom Mag. Drive
Agitator
utilities needed
Used successfully for CHO, hybridoma, HEK, human sarcoma, insect S2, yeast, E. coli
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Escaping the Legacy of Stainless Steel
1,000L Bioreactor 1994
1,000L Bioreactor 1982
1,000L Bioreactor 1994
1,000L Bioreactor 1982
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The Fully Disposable Process
Seed reactor
N-1 Reactor
(Wave System20 shown) (XcellereXDR-200 shown)
Chromatography
Production Reactor
Perfusion Centrifuge
Depth Filtration
(XcellereXDR-2000 shown)
(Centritech Cell I shown)
(Millipore POD shown)
0.2u Filtration
(BioFlash 8cm shown) (Sartorius Sartopore shown)
Virus Filtration
(Pall DV20 shown)
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Buffer/Media Prep Buffer/Process Storage
(Xcellerex XDM-500 shown) (Hyclone Labtainer shown)
What is FlexFactory ?
™
Combination of 3 technologies:
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Disposables
• Used wherever feasible (everywhere but bind & elute chromatography)
• Eliminates need for hard piping, CIP, SIP, most utilities
•
Controlled Environment Modules
• “Shrinking the clean room down around the unit op”
• Decreases gowning, increases operator mobility
• Protects product from greatest source of environmental contamination (the
operator)
•
Process Automation & Electronic Batch Records
• Reduces operator hands-on operations
• Reduces chances for human error
• Provides mechanism for automated QA, data mining
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Traditional Manufacturing Plant
WFI
CIP
Buffer Storage
Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
HVAC
Clean Steam
Cell Culture
Purification
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Buffer / Media Prep
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
PW
Form / Fill
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Specifications Manufacturing
Reports
Replacing Stainless w/ Disposables…
WFI
CIP
Buffer Storage
Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
HVAC
Clean Steam
Cell Culture
Purification
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Buffer / Media Prep
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
PW
Form / Fill
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Specifications Manufacturing
Reports
…Eliminates Utilities
Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
Cell Culture
Purification
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
HVAC
Form / Fill
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Specifications Manufacturing
Reports
Adding Microenvironments…
Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
Cell Culture
Purification
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
Air Locks & Hallways
HVAC
Form / Fill
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Specifications Manufacturing
Reports
Air Locks & Hallways
…Eliminates Clean Rooms & Complex HVAC
Cell Culture
Purification
Form / Fill
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Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
Specifications Manufacturing
Reports
Adding E-Batch Records & Automation…
Cleaning
Records
Sterilization
Records
Validation &
Maintenance
Records
Production
SOPs
Batch
Records
Deviations,
CAPAs
Air Locks & Hallways
eFactory™
Cell Culture
Purification
Form / Fill
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Specifications Manufacturing
Reports
…Eliminates Paper, Provides Electronic
Data & Web Access Through Secure Portal
FlexFactory™ Plant
Air Locks & Hallways
Operators work in “gray space” and can move easily from one unit op
to another between upstream and downstream or between products
eFactory™
Cell Culture
Purification
Form / Fill
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FlexFactory – Rapid Deployment Manufacturing
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Xcellerex GMP FlexFactory™
(newly fabricated downstream modules, GMP manufacturing facility
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Economic Analysis
• Economics evaluated with “BioSolve” model from
Biopharm Services
• Cost of goods model (based on Excel)
• Calculates costs & plant data based on database of industry
averages
• Researched & validated default values can be edited by user
• Customized with Biopharm Services for FlexFactory (preliminary
results reported in this case study)
Choose
process
type
Select scale,
titer, use of
disposables
Define
unit
operations
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Define
equip,
matls, etc.
Run
scenarios
Assumptions
BioSolve Dashboard – entry fields:
Scenario assumption:
• Typical mAb process
• 2 g/L, 2000L scale
• 4 prodn bioreactors
• 2 DSP lines
• Fully traditional vs.
• Fully disposable
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Results — Plant Footprint
• 45% reduction in total space required
• Shift toward lower air classification
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Results — Capital
Stainless Steel
FlexFactory
~75% reduction in capital cost
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Results — Cost of Goods Sold
24% reduction in COGS
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FlexFactory Layout
™
Space Requirements
(Cross-checking against previous studies)
Conventional (4 x 2000L lines)
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•
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•
•
•
•
•
•
•
•
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Downstream Processing
Upstream Processing
Air Locks
CIP/SIP
Wash Suite
Equipment Prep
Clean Utilities
Media Prep
Plant Utilities
Buffer Prep
Office
Labs
Corridors
Lockers/Gowning
Warehouse
TOTAL
FlexFactory (4 x 2000L lines)
4,500
4,500 sf
1,700
900
1,400
1,400
2,000
2,200
2,000
2,200
2,000
2,000
7,300
2,000
3,900
•
Processing Suite
•
•
•
•
•
•
•
•
•
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40,000
TOTAL
9,000 sf
(Upstream & Downstream)
Air Locks
CIP/SIP
Wash Suite
Equipment Prep
Plant Utilities
Clean Utilities
Media Prep
Buffer Prep
Office
Labs
Corridors
Lockers/Gowning
Warehouse
200
0
0
1,400
1,800
0
0
0
2,000
2,000
2,200
1,200
3,900
24,700
38% reduction of space
Courtesy of Lockewood Greene
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Conventional vs. Xcellerex FlexFactory™
for 4 x 2000L lines, cell vial to purified API bulk
Courtesy of Lockewood Greene
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FlexFactory “TransPlant” Manufacturing
™
Portable turnkey manufacturing modules enables a new
solution to the buy vs. make dilemma
Xcellerex / CMO
Customer Facility
design, build validate
FlexFactory™ modules
design, build, validate
Xcellerex / CMO
Customer contract
mfg., training
™
Customer
FlexFactory
The Ultimate
Tech Transfer
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Re-qualify / cal, start GMP mfg.
Environmental Impact
• What is the impact of throwing away
plastic with each batch?
• What waste is reduced in the switch
to disposables?
• How much water is used in cleaning?
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Results — Water Consumption & Waste
• ~85% reduction in water usage & waste
• 3x increase in plastic usage & waste
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Carbon Footprint
After Leveen & Monge, ISPE Tampa Conference, 02 March, 2009
*commuting workers contributed 70-80,000 lbs carbon in the same analysis
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Environmental Benefit of Disposables
• The fabrication cost of stainless and
plastic are roughly equivalent per batch
• Energy for purified water accounts for
most of the carbon in both processes
(40% disposables, 74% stainless)
• The carbon generation from plastic
incineration is more than offset by
energy savings from purified water
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Conclusions
• Disposables enable novel FlexFactory biomanufacturing platform
• Significant savings in capital, plant
footprint, water use
• Reduction in operating costs, COGS
• Positive environmental impact (carbon
footprint) from reduced water & energy use
• Portable manufacturing capacity enables
quick start-up and transportability
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Thank You
170 Locke Drive, Marlborough, MA 01752
www.xcellerex.com
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