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FlexFactory®
Defining the future ofbiomanufacturing
Daniel Bauer
Xcellerex, Inc.
June 2011
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• 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
Company Facts
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Traditional Stainless Steel Facilities – Time andCosts Traditional Stainless Steel Facilities
• 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 high-risk stage
• Expensive to operate and modify
• Limited long-term asset utilization
• Low terminal value (even lower in today’sdisposable environment)
• Many are obsolete before they are validated
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Barriers to biotech success
Mismatch between legacy mfg. model and futureindustry needs
Conventionalapproaches
• Large, single-productplants
• Inflexible, fixed pipe
• Built for blockbusters
New future requires:
• Low cost & flexible
• Validated productcomparability
• Local production
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• Driving the rush to low cost,high quality manufacturing
• Get in Front Ride the Wave…
• Or be Crushed by the Wave
The Building Wave of Opportunity…Biosimilars and Biobetters
Effectively creating a bio arms race
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Getting drugs to market – 15% probability, 7 yrs, $1B
Chips CDU SNPGene/TargetIdentification
Drug(s)discovery
Lead drugIdentification
Drug TestingPreclinical
HumanClinical Trials
Commercialdrug sales/marketing
ChemistryCell Line
developmentProcess
DevelopmentPre-ClinicalTox. studies
Phase 3clinical trials
Phase 3Clinical trials
FDAApproval
MarketLaunch
Phase 3clinical trials
Phase 1, 2a, 2bclinical trials
FDA ApprovalMarket launch
Faster, better, cheaper drugdevelopment and manufacturing
FlexFactory® Transplanttransferable GMP
facilities
Mfg. Services produceclinical material inFlexFactory®
Xcellerex Focus
De-RiskedRapid PlantLicsensure
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Xcellerex Strategic Rationale – QbDFlexFactory®
Dramatic improvements in deployment speed, quality,
flexibility and overall economics can only be achieved by
taking a fresh, holistic comprehensive QbD approach to
biomanufacturing
EquipmentQbD
FacilityQbD
RegulatoryQbD
Services/Training QbD
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Plant Footprint ReductionJust disposables vs. FlexFactory
Plant Footprint ReductionJust disposables vs. FlexFactory
for 4 x 2000L lines, cell vial to purified API bulk
MEDIA BUFFER
LABSU.S.P.
D.S.P.
U.S.P.
D.S.P. WAREHOUSE
LOCKERS/GOWNING
OFFICES
PLANTUTILITIES
CLEANUTILITIES
EQUIP.PREP
C.I.P./S.I.P.
WASH
LOCKERS/GOWNING
OFFICES
PLANTUTILITIES
LABS
WAREHOUSE
FlexFactory™PROCESSING
SUITE
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2000L GMP FlexFactory #2 at Xcellerex
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All XDRs have a 5:1 turn down ratio(Each can operate at 20% working volume)
XDR-5000 in development
Breakthroughs in Biomanufacturing from Xcellerex
XDR-200 XDR-500 XDR-2000XDR-1000
XDR GMP Single-Use Bioreactor
XDR-50
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CEMs Replace Clean Rooms
• Reduces mfg plantfootprint 35%
• Decreases gowning,reduces labor 30%
• Protects productfrom greatest sourceof environmentalcontamination (theoperator)
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CEMs are CleanroomsEliminating the need for Wall Segregation
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CEM Operational Benefits• Segregation of each unit operation from the general environment,
• CEMs have independent (from room) fresh air supply, independent ofthe room supply is a major segregation factor and virus reductionprotection design feature for prevention of cross contamination across15-20 logs of virus clearance or across pre and post virus inactivation,
• In excursion event management, segregation allows protection ofremaining unit operations from excursion operation,
• CEMs provide spill containment, prevent exposure to other unit ops inpressurized CEMs
• CEMs can be decontaminated in situ
• Requirement to turn around only one unit op at a time versus multipleunit ops in large clean rooms
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CEM Operational Benefits• Data historization of environmental conditions real time with process
data,
• Ability to operate all process operations in one larger manufacturingspace,
• Reduction of gowning requirements in a manufacturing facility,
• Elimination of multiple clean rooms for process operations,
• Reduction of airlocks for material, personnel and product flowstrategies,
• Increase in operator efficiency with increased focus on processoperations,
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CEM Operational Benefits• 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, andcan be further decontaminated with chlorine dioxide if needed for morepathogenic bugs
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Single-Use Unit Operations
• Eliminates CIP/SIPoperations andinfrastructure
• Reduced labor
• Reduced carbonfootprint
• Improved safety
• Enhanced flexibility
• An “open” platform
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Integrated real time automation
• Reduces operatorhands-on operations
• Provides mechanismfor automated QA,data mining
• Real-time capture ofprocess and humandeviation
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• Disposableseliminate crosscontamination
• CEM - Operatorsremoved fromclean room
• On-line eFactoryquality assurancetrackscompliance
The Xcellerex QbD SolutionFlexFactory® Biomanufacturing Platform
Quality
Risk R
edu
ction
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The Xcellerex QbD SolutionFlexFactory® Biomanufacturing Platform
Speed
• 6-12 months vs.2-5 years fornew capacity
• Enables moreinformedinvestmentdecisions
• Faster productchangeovers
• Rapid expansionof mfg capacity
Risk R
edu
ction
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• Compactclean roomarchitecture
• Modular
• Portable
• Multiple productmanufacturing
• Ability toTransPlant™ tocustomer
• Avoid long-termCMO lock-up
The Xcellerex QbD SolutionFlexFactory® Biomanufacturing Platform
Flexibility
Risk R
edu
ction
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• Lower capital cost(50%-75%)
• Lower operatingcosts (20%)
• Higher assetutilization
• Shorter timelineto product revenue
• Improvedenvironmentalimpact
The Xcellerex QbD SolutionFlexFactory® Biomanufacturing Platform
Economics
Risk R
edu
ction
FlexFactory designs underway for 3rd parties
CourtesyParsonsEngineering
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Facilities
Modular Cleanrooms
Manufacturing Floor 4 x 2000L Scale
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FlexFactory and Facility 4 x 2000LGreenfield
• 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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EquipmentPlatform
ServicesPlatform
Integration & Process Know-How
Unique Business Structure LeveragesCustomer Adoption
FlexFactory
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FlexFactory Services• FlexFactory® Services
portfolio adds speed,security to newdeployments:• Process developmentand optimization
•Bridge GMPmanufacturing forclinical trials
•Validation and training
• TransPlant™ toCustomer site
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TransPlant
Bringing it all together
A Typical FlexFactory® Deployment
BuildFlexFactory Line
Client builds facilityat their own pace
(with Xcellerex design help)
Compress deployment time
Reduce risk/delay critical decisions
Customer control
AT XCELLEREX
AT CLIENT
Validate/OperateFlexFactory Line
Train Client Team
RestartFlexFactory
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FlexFactory® Regulatory MilestonesDec. 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 client31
7 US INDs filed,1 UK filing
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Advantages of FlexFactory®
• 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
• Simultaneous multi-product manufacturing and flexibility
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170 Locke Drive, Marlborough, Massachusetts 01752
www.xcellerex.com
1.866.Xcellerex
THANK YOU!