FlexFactory®
Defining the future of
biomanufacturing
Daniel Bauer
Xcellerex, Inc.
June 2011
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Company Facts
2
•
Founded 2003 as a Disposable Flow Path focused CMO
•
Facility: 100,000 sq. ft. laboratory, GMP mfg and office
•
140 employees
•
Global sales and service network including EU, APAC -based operations
•
8 INDs filed based FlexFactory Platform
•
Over 150 XDR bioreactors, 350 XDM mixers deployed in the last three years
•
Five Operational FlexFactory platform
•
Recent press releases by RPharm, Gallus and Diosynth
•
1st Commercial Product Manufactured in a Disposable Bioreactor
•
GROW CELLS DAILY
Traditional Stainless Steel Facilities – Time and
Costs
Traditional Stainless Steel Facilities
3
•
Prohibitive cost to build new mfg. capacity…
$1500-2,000/sq ft
•
$200-$400M total installed capital cost
•
4 year timeline for new capacity
•
Risk of committing capital during early highrisk stage
•
Expensive to operate and modify
•
Limited long-term asset utilization
•
Low terminal value (even lower in today’s
disposable environment)
•
Many are obsolete before they are validated
Barriers to biotech success
Mismatch between legacy mfg. model and future
industry needs
Conventional
approaches
4
•
Large, single-product
plants
•
•
Inflexible, fixed pipe
Built for blockbusters
New future requires:
•
•
Low cost & flexible
•
Local production
Validated product
comparability
The Building Wave of Opportunity…
Biosimilars and Biobetters
Effectively creating a bio arms race
• Driving the rush to low cost,
high quality manufacturing
• Get in Front Ride the Wave…
• Or be Crushed by the Wave
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Getting drugs to market – 15% probability, 7 yrs, $1B
Cell Line
Gene/Target
development
Identification
Chips
Process
Drug(s) Pre-Clinical
Lead drug
Development
Tox.
studies
discovery Chemistry
Identification
FDA
Phase
3 3 Commercial
Phase
2a,Phase
2b 3 Human
Drug 1,
Testing
Phase
FDA Approval
Approval
Clinical
Trials
sales/
Clinical
trials
clinical trials
clinical
trials
launch
clinical
trialsdrugMarket
Preclinical
Market
CDU
SNP
marketingLaunch
Xcellerex Focus
Faster, better, cheaper drug
development and manufacturing
Mfg. Services produce FlexFactory® Transplant
transferable GMP
clinical material in
facilities
FlexFactory®
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De-Risked
Rapid Plant
Licsensure
Xcellerex Strategic Rationale – QbD
FlexFactory®
Dramatic improvements in deployment speed, quality,
flexibility and overall economics can only be achieved by
taking a fresh, holistic comprehensive QbD approach to
biomanufacturing
Facility
QbD
Equipment
QbD
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Services/
Training QbD
Regulatory
QbD
Plant Footprint Reduction
Just disposables vs. FlexFactory
for 4 x 2000L lines, cell vial to purified API bulk
MEDIA
LOCKERS/
GOWNING
U.S.P.
BUFFER
EQUIP.
PREP
U.S.P.
LABS
LOCKERS/
GOWNING
FlexFactory™
PROCESSING
SUITE
C.I.P./
S.I.P.
OFFICES
D.S.P.
CLEAN
UTILITIES
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WASH
LABS
D.S.P.
PLANT
UTILITIES
WAREHOUSE
OFFICES
WAREHOUSE
PLANT
UTILITIES
9
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2000L GMP FlexFactory #2 at Xcellerex
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XDR GMP Single-Use Bioreactor
Breakthroughs in Biomanufacturing from Xcellerex
XDR-50
XDR-200
XDR-500
All XDRs have a 5:1 turn down ratio
(Each can operate at 20% working volume)
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XDR-5000 in development
XDR-1000
XDR-2000
CEMs Replace Clean Rooms
• Reduces mfg plant
footprint 35%
• Decreases gowning,
reduces labor 30%
• Protects product
from greatest source
of environmental
contamination (the
operator)
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CEMs are Cleanrooms
Eliminating the need for Wall Segregation
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CEM Operational Benefits
15
•
Segregation of each unit operation from the general environment,
•
CEMs have independent (from room) fresh air supply, independent of
the room supply is a major segregation factor and virus reduction
protection design feature for prevention of cross contamination across
15-20 logs of virus clearance or across pre and post virus inactivation,
•
In excursion event management, segregation allows protection of
remaining unit operations from excursion operation,
•
CEMs provide spill containment, prevent exposure to other unit ops in
pressurized CEMs
•
CEMs can be decontaminated in situ
•
Requirement to turn around only one unit op at a time versus multiple
unit ops in large clean rooms
CEM Operational Benefits
16
•
Data historization of environmental conditions real time with process
data,
•
Ability to operate all process operations in one larger manufacturing
space,
•
Reduction of gowning requirements in a manufacturing facility,
•
Elimination of multiple clean rooms for process operations,
•
Reduction of airlocks for material, personnel and product flow
strategies,
•
Increase in operator efficiency with increased focus on process
operations,
CEM Operational Benefits
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•
Single pass air supply and exhaust,
•
HEPA-filtered supply air,
•
HEPA-filtered exhaust air,
•
Responsive control of environmental conditions (differential pressure,
air changes),
•
CEMs are cleaned using standard clean room sanitization agents, and
can be further decontaminated with chlorine dioxide if needed for more
pathogenic bugs
Single-Use Unit Operations
• Eliminates CIP/SIP
operations and
infrastructure
• Reduced labor
• Reduced carbon
footprint
• Improved safety
• Enhanced flexibility
• An “open” platform
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Integrated real time automation
• Reduces operator
hands-on operations
• Provides mechanism
for automated QA,
data mining
• Real-time capture of
process and human
deviation
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The Xcellerex QbD Solution
FlexFactory® Biomanufacturing Platform
• Disposables
• CEM - Operators
removed from
clean room
• On-line eFactory
quality assurance
tracks
compliance
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Risk Reduction
Quality
eliminate cross
contamination
The Xcellerex QbD Solution
FlexFactory® Biomanufacturing Platform
• 6-12 months vs.
• Enables more
informed
investment
decisions
• Faster product
changeovers
• Rapid expansion
of mfg capacity
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Risk Reduction
Speed
2-5 years for
new capacity
The Xcellerex QbD Solution
FlexFactory® Biomanufacturing Platform
• Compact
• Modular
• Portable
• Multiple product
manufacturing
• Ability to
TransPlant™ to
customer
• Avoid long-term
CMO lock-up
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Flexibility
Risk Reduction
clean room
architecture
The Xcellerex QbD Solution
FlexFactory® Biomanufacturing Platform
• Lower capital cost
Risk Reduction
(50%-75%)
• Lower operating
costs (20%)
• Higher asset
utilization
• Shorter timeline
to product revenue
• Improved
environmental
impact
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Economics
FlexFactory designs underway for 3rd parties
Courtesy
Parsons
Engineering
Facilities
Modular Cleanrooms
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Manufacturing Floor 4 x 2000L Scale
FlexFactory and Facility 4 x 2000L
Greenfield
•
Capital:
Facility +Process Equipment +Install & Qualify = 40 – 45 MM
•
Schedule:
Design Agreement to GMP Production ~ 18 months
Renovation
•
Capital:
Facility +Process Equipment + Install & Qualify = 14 – 20 MM
•
Schedule:
Design Agreement to GMP Production ~ 12 months
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Unique Business Structure Leverages
Customer Adoption
FlexFactory
Equipment
Platform
Services
Platform
Integration & Process Know-How
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FlexFactory Services
• FlexFactory® Services
portfolio adds speed,
security to new
deployments:
• Process development
and optimization
• Bridge GMP
manufacturing for
clinical trials
• Validation and training
• TransPlant™ to
Customer site
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Bringing it all together
A Typical FlexFactory® Deployment
AT XCELLEREX
Validate/Operate
FlexFactory Line
Build
FlexFactory Line
Train Client Team
TransPlant
AT CLIENT
Client builds facility
at their own pace
(with Xcellerex design help)
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


Compress deployment time
Reduce risk/delay critical decisions
Customer control
Restart
FlexFactory
FlexFactory® Regulatory Milestones
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Dec. 2002
Previous owner filed CTX in UK for mAb
Dec. 2003
Type C meeting with FDA – strong support
Apr. 2004
Presentation to FDA Advisory Committee for Pharm. Sci.
Jan. 2007
Client filed IND
Jan. 2007
Training seminar for CDER DMPQ
May 2007
Seminar for NAFDAC (Nigeria)
June 2007
Seminar for WHO IVR
Oct. 2007
Training seminar for CBER DMPQ
Nov. 2008
2nd client filed IND amendment
May 2008
EMEA GMP Inspectorate Feedback
Jan. 2009
Client filed IND for their second product
Feb. 2009
Training seminar for Boston FDA compliance inspectors
Nov. 2009
Xcellerex filed IND for Yellow Fever inactivated vaccine
Dec. 2009
Mexican FDA COFEPRIS inspection for swine flu H1N1
Mar 2010
EMA QP Certification for Phase 3 mfg. underway
Mar 2011
Planned start of Phase 3 mfg for EU client
7 US INDs filed,
1 UK filing
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Advantages of FlexFactory®
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•
50% reduced capital
•
30% reduction in mfg. labor, gowning costs, HVAC
•
70% reduced facility build out time
•
30% reduction in plant footprint
•
25% reduction in QA
•
Reduced carbon footprint
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Simultaneous multi-product manufacturing and flexibility
THANK YOU!
170 Locke Drive, Marlborough, Massachusetts 01752
www.xcellerex.com
1.866.Xcellerex
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