FlexFactoryfi · 2018-02-19 · 3 Traditional Stainless Steel Facilities Time and Costs...

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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!