Bovis Lend Lease is proud to have worked in - Baxter, BioPharma … · 2016-04-05 · Bovis Lend...

Bovis Lend Lease is proud to have worked in joint venture with Jacobs Engineering to deliver Wyeth’s world-class biopharmaceutical campus at Grange Castle, Dublin.

Bovis Lend Lease’s role on the Wyeth project gives strength to our long standing presence in Ireland and provides us with a platform for our global service delivery in Ireland’s future development as a centre of excellence.

Our services:

• Master planning

• Commercial • Project management

• Procurement • Start-up

• Consultancy

• Design

• Engineering

• Construction

• Quality assurance & compliance

• Integrated commissioning & validation

Contact: Sue Shufflebotham-Devereaux

Telephone: +44 (0) 161 254 1700Facsimile: +44 (0) 161 254 1701

Email: [email protected]

www.facilityoftheyear.org4 PHARMACEUTICAL ENGINEERING Supplement MARCH/APRIL 2006

Articles

Winner:6 Baxter BioPharma Solutions

Phase IV Vial and Syringe Filling Facility

Finalist:12 AstraZeneca

Large-Scale Laboratory (LSL) Facility

Special Recognition:16 Biolex Therapeutics

Phase II GMP Facility Expansion

Finalist:18 Daiichi Asubio Pharma Co., Ltd.

New Bio Plant (NBP)

Finalist:22 Janssen Pharmaceutica

Small Volume Area (SVA) – Powder Unit

Finalist:26 Wyeth Pharmaceuticals

Wyeth BioPharma Campus at Grange Castle

30 An Interview with Peter BigelowFacility of the Year Judging Panel Chair

Cover Photograph

Photo courtesy of BaxterBioPharma Solutions

Table of Contents

SPECIAL EDITION STAFF

Business InitiativesDirector of Business Initiatives

Scott LudlumBusiness Initiatives Coordinator

Lauren Blankley

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Susan PazeraMarketing/Communications Associate

Heather Fortson

PublicationsEditor and Director of Publications

Gloria N. HallPublications Manager

Lynda D. Goldbach

SalesDirector of International Sales

David J. Hall

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www.ispe.org

A Supplement to MARCH/APRIL 2006

Facility of the Year Special Edition

THE OFFICIALMAGAZINE OFISPE

www.facilityoftheyear.org MARCH/APRIL 2006 PHARMACEUTICAL ENGINEERING Supplement 5

Advertiser's IndexAPPLIED CONTAINMENT ENGINEERING ...................... 5BNS ENGINEERING ................................................. 25BOULTING GROUP ................................................. 11BOVIS LEND LEASE .................................................. 3EISAI MACHINERY .................................................. 29EMERSON PROCESS MANAGEMENT ....................... 32FOSTER WHEELER ................................................. 25GEA LIQUID PROCESSING ......................................... 2JACOBS ENGINEERING GROUP ............................... 15JANSSEN PHARMACEUTICA ................................... 23JGC CORP. ............................................................ 19O’NEAL, INC. ......................................................... 17PHARMADULE ......................................................... 7SKAN AG .............................................................. 24STERIS .................................................................. 27THERMAL TRANSFER ............................................. 13US FILTER ............................................................... 9YOKOGAWA .......................................................... 21

ISPE would like to thank the followingFacility of the Year Finalists’

key project participantsfor their generous advertising support

which made this Special Edition possible.

The Facility of the Year Awardis sponsored by:


Facility of the Year Winner

WINNER

Baxter BioPharma Solutions

A New Shot at Contract Services

3-D design throughout, and the combination of innovativetechnology and practical functionality – a difficult balance for

an aseptic environment. These are among themany qualities that make this a truly world-class facility.”

The Phase IV Project consisted of partial demo-lition and renovation of an existing buildingas well as new construction, and was com-pleted in only 22 months from start of detaileddesign to US FDA approval. The project com-bines conventional construction for adminis-trative areas with state-of-the-art modularconstruction for manufacturing areas. Addi-tionally, another off-site building was reno-vated for expansion of packaging operations,

Astate-of-the-art response to an un-der-served market... groundbreak-ing use of modular design... effec-

tive use of the latest and most advancedhigh-speed syringe filling technology.Any one of these attributes is notewor-thy, but taken in combination, they spellone thing: pharmaceutical manufactur-ing excellence. As the winner of the2006 Facility of the Year Award, BaxterPharmaceutical Solutions (BPS) hasdemonstrated world-class quality withits Phase IV Vial and Syringe FillingProject in Bloomington, Indiana, US. Commissioned in mid-2005, the Phase IV facility is the company’s response to amarket opportunity to provide large-scale syringe filling,aseptic formulation, vial filling, lyophilization, terminal steri-lization, and flexible formulation capacity for a variety ofchallenging products such as insoluble solutions and vac-cines.

“With its new Phase IV operation, Baxter, in conjunction withdesign/build partner Pharmadule AB, has demonstrated trueleadership in the rapidly growing contract manufacturingsector,” said Peter Bigelow, Senior Vice President of Con-sumer Healthcare Manufacturing for Wyeth and Chairmanof the 2006 Facility of the Year Award Judging Panel. “It israre to find such an impressive array of cutting-edge fillingtechnologies all within one facility. We were also very im-pressed with Baxter’s use of bolt-on removable components,

PROJECT: Phase IV Vial and Syringe FillingFacility

LOCATION: Bloomington, Indiana,United States

DESIGN-BUILDPARTNER: Pharmadule AB

Continued on page 8.

Facility modules built in a workshop environment.

Exterior view.

Corporation for reaching the final ofCongratulations Baxter Healthcare

the Facility of the Year Award

Congratulations Baxter HealthcareCorporation for reaching the final ofthe Facility of the Year Award



WINNER

and Baxter added large-scale cold storage capacity for tem-perature sensitive products.

Filling a NeedAs pharmaceutical companies become increasingly focused onthe R&D pipeline and its impact on sales and marketing,contract manufacturing is becoming a cost-effective alterna-tive to large capital projects - especially if production volumesdon’t warrant the investment. BPS, a full-service contractmanufacturing organization serving the pharmaceutical andbiopharmaceutical industries, recognized a need to providethese services all “under one roof,” a need that had previouslybeen unmet by other contract manufacturers.

The Bloomington facility is a full service contract manufactur-ing plant providing form, fill, and finish services to thepharmaceutical industry for a variety of sterile productdosage forms. These products include solutions, suspensions,and freeze-dried powders encompassing human and veteri-nary small molecule, biologic, biotech, vaccine, and proteinpharmaceuticals. BPS wanted to ensure its facility’s capabili-ties could meet client production needs with the growingmarket preference for prefilled syringes.

For consumers, pre-filled syringes have advantages overtraditional packaging in vials, including reduced microbialcontamination risk due to less manipulation and exact dosingfor greater patient safety and compliance. From a manufac-turing perspective, pre-filled syringes improve a client’s bot-tom line as less overfill is required than with vials. Plus, avariety of customized features can be used to meet end users’needs, potentially resulting in product differentiation andmarket share expansion.

Technologies Leading the WayThe Baxter facility is the first to use a new high-speedsyringe-filling system, which can fill 500 syringes per minute,and is a considerable improvement over the 300 syringes perminute capacity of existing technologies. One of the key

attributes of the machine thathas increased throughput is thetube handling system, whichnow handles tubes in parallelinstead of serially. The increasedthroughput of the filler hassaved considerable capital costson the project by alleviating theneed for two machines and ad-ditional clean space and gown-ing room.

Another focus of the facility wasto provide a new formulation

and filling service for manufacturers of insoluble and un-stable drugs. The new technology revolves around Baxter’sNanoedge process, which increases solubility and reducesexcipient side effects in formulation. Drug particles arereduced to 100 nanometers in diameter, and then coated witha thin layer of proprietary excipient, creating drug particlesthat dissolve more rapidly when injected or infused.

Nanoedge has allowed Baxter to solve seemingly intractableformulation problems. This is based on the dilemma ofcurrent formulation situations that would ordinarily takeone part drug to 10,000 parts of water to dissolve. Instead ofrequiring a patient to endure a 10 L infusion, Nanoedgewould allow for formulations in 10 ml doses. The flexibleformulation space included as part of this facility enabledBaxter to commercialize this technology.

“Farming Out” Process DesignThe manufacturing portion of the facility expansion was adesign/build project provided and qualified by PharmaduleAB, a provider of modular facilities for the pharmaceuticaland biopharmaceutical industry. Baxter pursued modulartechnology because it provided the quickest return on invest-ment with minimal risk and demand on internal resources.

Staging area for new packaging line. New packaging line.

High speed syringe filling line.Concludes on page 10.

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The benefits included: shaving 12 months off the deliveryschedule; reduced demand on client resources; integratedvalidation in the basic design phase; elimination of a largeportion of installation, commissioning and qualification atthe site; and a reduction in local resources and disruption atworksite and to the existing operation.

Offsite Facility Testing and 3-D DesignModular technology and delivery used for design and construc-tion involved the offsite fabrication of the entire manufactur-ing process facility, inclusive of structural steel, poured con-crete floors, internal finishes, process and utility piping,electrical, automation, HVAC and process and utility equip-ment, and systems. The modular facility was fabricated in afactory in Sweden, pre-assembled, tested, pre-qualified, dis-assembled, packed, and shipped across the Atlantic Ocean,then reassembled, and commissioned and validated at thesite.

Three-dimensional design was used throughout the facility,which facilitates any later remodelling or expansion of thefacility. Airflow patterns in critical areas such as the fillingsuites were stimulated before finalizing the 3-D design. Thisallowed for the design to change before start of construction tooptimize airflow patterns.

Modularization in combination with the use of 3-D designassured a high level of accuracy in the placement and accessto equipment and services. Time and efficiency gains ofmodularizing the manufacturing areas were realized in PhaseII and III expansion projects, which drove the decision to againpursue modularization for the Phase IV project.

The Phase IV facility was designed with foresight to mini-mize any impact for expansion of the vial filling and lyo-philization capacity related to the market demands. Thefacility modules are designed with 12' x 14' removeablepanels that are bolted with gaskets to allow for clean andquick access to the building. Equipment can be added or

removed easily, as well as the quick addition or manufactur-ing modules for a fast response to market demand withoutdisturbing the ongoing production.

The facility is designed to add a mirror manufacturing suiteon the opposite side of the building, which will then utilize thepersonnel and material corridors as a central spine. Wide,open rooms allow for ample working space and flexibilitywithin the facility.

Tracking and Quality ControlThe facility uses a new ERP/MRP enterprise planning systemfrom Oracle to facilitate the tracking and management ofmaterial throughout the manufacturing process, providing100 percent accountability of product tracking from rawmaterials through packaging. The platform features a pro-duction-scheduling program that will monitor constraintsand anticipate potential problems, which is a task thatpreviously required six full-time managers.

Environmental ConsiderationsBy constructing the modular manufacturing facility off-site ina dedicated manufacturing facility, Pharmadule was able togreatly reduce the project’s impact on the local environment.

Site work logistics were established to assure that no wasteor debris entered a creek that runs through the campus. Siltfences and other erosion control measures were employed.Electric and gas utilities were tunnelled under the creek to notdisturb fish and wildlife.

Leading the Way inParenteral Contract Services

As the winner of the 2006 Facility of the Year Award, thePhase IV Project is the realization of BPS’s vision to providecontract manufacturing services for pre-filled syringes andlyophilized vials. Through a creative and innovative mix ofconventional construction for support areas combined withstate-of-the-art modular construction of the manufacturingareas, the project has propelled BPS to become the world’slargest supplier of pre-filled syringes - with a greatly ex-panded capacity for delivering the unit dosage forms that arecritical for vaccines being re-developed without preserva-tives. As a result, Baxter is now the parenteral contractservices leader of pre-filled syringes in North America with atotal capability of filling up to 300 million 1- to 3-mL syringeseach year including automated inspection, labelling, andpackaging. For pharmaceutical companies choosing tooutsource these operations, the BPS Phase IV Project pro-vides a state-of-the-art, award-winning solution.

Rear view of the modular manufacturing area.

WINNER


FINALIST

Facility of the Year Finalist

AstraZeneca

Delivering a Multi-Purpose API Plant

ogy, and neuroscience. It consists ofone large, three-story building com-prising three processing areas contain-ing 16 reactors and ancillary equip-ment. In addition, there are separatechromatography and hydrogenationsuites. Significantly, it is an API manu-facturing facility capable of a range ofdifferent operating scales with a scopeof containment solutions capable of awide variety of chemical and physicaltransformations and rapidly configur-able to deliver any combination thereof.

Creativity, Ingenuity,and Teamwork

In conjunction with Jacobs Engineer-ing, AstraZeneca made an extraordi-nary effort during the conceptual stageof the project to ensure the require-ments of such an asset were relevantfor future needs of the company. Thisresulted in key features, including:

• a diverse range and combination ofprocessing equipment and technolo-gies

• a modular layout concept• an innovative combination of con-

tainment approaches that allowshandling of substances with an OELdown to 30ngm-3

• state-of-the-art chromatographytechnologies

• novel project delivery through“alliancing”

The modular layout concept was notonly cost effective but allowed the facil-ity to be doubled in scale on a reservedfootprint using the existing design. Theentire infrastructure delivered by theoriginal project was sized for the largerplan.

State-of-the-art chromatography tech-nologies were used to increase the flex-ibility of the facility. For rapid deliveryof critical path clinical supplies, theLSL includes a large-scale chromatog-raphy facility for separation of inter-mediates and final APIs. When keysteps are made with optimal chemistryand chromatography as a part of theprocess, strategic route selection deci-sions can be made. Thus, otherwisenon-viable chemical routes can becomea commercial reality faster and earlierthan anticipated.

A significant component of the chro-matography investment is the Simu-lated Moving Bed (SMB), an innova-tive continuous manufacturing tech-nique which allows separation of bi-

In response to an increased numberof development projects, more com-plex manufacturing processes and

due to increased drug substance po-tency, AstraZeneca is investing in up-grading, replacing, and building newkey facilities. The Large Scale Labora-tory (LSL) at Macclesfield, UK repre-sents a significant element of this pro-gram. As a unique brown-field devel-opment, the project utilizes a holisticapproach to the venture – from concep-tual analysis through establishment ofroutine operation.

The LSL facility manufactures emerg-ing compounds from AstraZeneca’stherapy areas, including gastrointesti-nal, cardiovascular, respiratory, oncol-

PROJECT: Large-Scale Laboratory (LSL)Facility

LOCATION: Macclesfield, United Kingdom

DESIGN-BUILDPARTNER: Jacobs Engineering Group, Inc.

Exterior view.



nary mixtures with far lower use ofstationary phases and solvents. Par-ticularly for chiral chromatography,this reduces costs significantly andcan make otherwise uneconomic sepa-rations viable.

The project was delivered via a novelconcept developed within AstraZenecaknown as “alliancing.” The keys tosuccessful alliancing were in develop-ing a single, integrated multi-disci-plinary and multi-skilled project teamfrom a small range of partner compa-nies and AstraZeneca personnel. Thiswas accomplished by forming mutu-ally-beneficial relationships based onopen, honest, and trusting relation-ships in which AstraZeneca’s need toobtain value for money, superior safety,schedule, and regulatory complianceadherence was equal to the partners’need to make a fair return. Concludes on page 14.

The ResultThe Large Scale Laboratory has been ahighly successful venture between

AstraZeneca and its Alliance Partnersto deliver a state-of-the-art facility. The

Interior view.

FINALIST


FINALIST


LSL project has demonstrated its abil-ity to shorten production time throughinnovation, processing efficiencies, andwell understood and dependable equip-ment. As a result, the facility has en-abled Campaign 2 (C2) manufacture ofdrug substance for volunteer studies to

Interior view.

be taken off the critical path. In addi-tion to a significant business advan-tage, the facility provides an optimumrange of manufacturing scales withrapidly configurable containment op-tions to suit the compound being pro-cessed, without compromising operabil-

ity. The LSL project is unique in that itrepresents a complete solution toAstraZeneca’s C2 manufacturingneeds, delivering flexibility and adapt-ability, yet achieving these goalsthrough a novel project approach in ahighly cost effective manner.

“The LSL project hasdemonstrated its ability toshorten production time

through innovation,processing efficiencies, and

well understood anddependable equipment.”

Peter Bigelow, Judging Panel ChairSenior VP Consumer Healthcare Manufacturing, Wyeth

Tony FeliciaVP R&D Administration, AstraZeneca

Christian IlsoeVice President, Quality and Validation Assurance, NNE A/S

Brian H. Lange, PEDirector – Sterile and Packaging Operations Engineering, Merck & Co., Inc.

Ulrich RudowVP Worldwide Engineering and Real Estate, Johnson & Johnson

Raymond H. ScherzerSenior Vice President of Engineering, Technology and Capital Management

in Global Manufacturing and Supply, GlaxoSmithKline

Andrew A. Signore, PE, PMP, DBIAPresident, IPS

Andy SkiboVP Corp. Engineering and Capital Production, Amgen

Meet the 2006 Facility of the Year Award Judging Panel


Special Recognition

Facility of the Year Special Recognition

Biolex Therapeutics

Simplicity in Approach Leads to FacilityExcellence

Process InnovationThe Biolex Phase II expansion showcases key innovativetechnologies in the company’s manufacturing process. Ratherthan using traditional cell culture methods, the Biolexprocess employs the small, free-floating aquatic plant,Lemna. Lemna is a clonal plant known to be geneticallystable. The method involves introducing a specific genesequence into the cells of the plant which serve as thetemplate for constructing a target therapeutic protein. Byusing a whole, intact organism, the environmental require-ments for clonal replication and therapeutic expression areminimized. The plant grows in a wide range of conditions inits natural environment, and requires a simple aqueousmedia of basal salts, a light source, and CO2 to producehuman therapeutics.

By using this expression system, the upstream productionprocess equipment and utility systems required were mini-mized. The need for stainless steel tanks with CIP and SIPcapabilities, WFI, and clean steam systems were eliminated– as were the capital expense and long lead times associatedwith such equipment.

Fast-Track Project DeliveryThe strategy to use a transgenic plant to produce humantherapeutics resulted in a facility project involving mostlyarchitectural, HVAC, and electrical design and constructionelements rather than the often complex equipment and

In an industry in which each new facility or facility renova-tion project is bigger, more elaborate, and more complexthan the last, simplicity is sometimes the best strategy. In

expanding the production capabilities of its Pittsboro, NorthCarolina, US, manufacturing facility, Biolex Therapeuticsadopted the “simple and practical” approach for all aspects ofthe facility expansion and the operation of the completedfacility. As recipient of the 2006 Facility of the Year SpecialRecognition, Biolex has demonstrated how “simple is better”can yield the following benefits:

1. additional manufacturing capacity, which conforms toU.S. and European GMPs

2. flexible manufacturing space, which can be used for pro-duction of research grade, pre-clinical and clinical phasematerials

3. exceedingly quick and economical facility delivery

Biolex engaged O’Neal, Inc. to provide integrated design,engineering and construction services on a design/build basisfor the facility expansion project. The expansion allowedBiolex to convert an additional 7,500 square feet of a 50-year-old, brick textile mill located in the historic district of Pittsborointo manufacturing space for the production of several com-plex recombinant proteins, including bulk material forLocteron™, the company’s novel, controlled release formula-tion of interferon. Locteron just completed Phase 1 clinicaltrials and this additional capacity has allowed Biolex Thera-peutics to immediately ramp up material for Phase 2 clinicaltrials.

PROJECT: Phase II GMPFacility Expansion

LOCATION: Pittsboro,North Carolina,United States

DESIGN-BUILDPARTNER: O’Neal, Inc.

Exterior view.


Special Recognition

utility requirements typically associated with biologicalmanufacturing facilities. The project team was able to fur-ther capitalize on these advantages by using off-the-shelf,packaged utility systems to capture capital savings andshorten delivery times over custom designed utility equip-ment.

Additionally, Biolex used modular-constructed environmen-tal chambers for bioproduction suites within the new expan-sion area. These suites were slightly customized versions ofchambers that have traditionally been used in the agricul-tural industry and in academic institutions for plant growthand research applications. The suites provide Biolex opti-mal environment growth conditions in a controlled, con-tained environment. The modular design of the units al-lowed site construction to commence while the suites werebeing constructed in parallel. Once the suites arrived, theywere simply erected in place and tied into the installedutility systems. Further time savings were captured byusing an enhanced commissioning approach in the valida-tion of the suites.

By emphasizing simplicity of design, construction, and opera-tion, Biolex’s expansion project was completed from thebeginning of design through the completion of OQ validationin five months, from March to August 2005. The project wascompleted under budget with no safety incidents and withsuperior quality.

“The technology employed by Biolex Therapeutics is an excel-lent example of manufacturing innovation,” said PeterBigelow, Senior Vice President of Consumer HealthcareManufacturing for Wyeth and Chairman of the 2006 Facilityof the Year judging panel. “Instead of using traditional cellculture methods, the Biolex manufacturing process employsa unique expression system. We found that to be a veryintriguing new innovation in biotechnology.”

Interior view.


FINALIST


Daiichi Asubio Pharma Co., Ltd.

Multi-Products and Multi-Scale “Launch Plant”

For patients suffering from cardio-vascular disease, central nervoussystem, and immune systems dis-

orders, effective treatments cannotcome too soon. To shorten the productdelivery cycle for new drugs in thesetherapeutic areas, Daiichi AsubioPharma Co., Ltd. (ASB), a subsidiaryof the Daiichi Pharmaceutical Group,

struction, and commissioning andqualification.

A unique combination of cutting-edgeproduction processes makes the NBPunique among pharmaceutical facili-ties in Japan, and perhaps, the entireworld. The $30 million plant is equippedwith two fermenters (300 liter and 4,500liter), separation, reaction, purifica-tion and lyophilization systems, andwas completed in a remarkable 26

PROJECT: New Bio Plant (NBP)

LOCATION: Gunma Prefecture, Japan

DESIGN-BUILDPARTNER: JGC Corporation

constructed a new multi-product andmulti-scale plant in Gunma Prefec-ture, Japan. As a multi-product andmulti-scale “launch plant” for bulkbiopharmaceutical products, the NewBio Plant (NBP) provides small-scalemanufacturing for Phase 2 clinical tri-als as well as large-scale commercialmanufacturing. Leading Japanese en-gineering and construction companyJGC Corporation was selected to ex-ecute engineering, procurement, con-

months from start of conceptual studyto readiness for Performance Qualifi-cation (PQ).

State-of-the-ArtPeptide Production

A unique feature of the NBP is a pep-tide production process by which pep-tides are produced on a commercialscale from recombinant microorgan-isms. In the NBP, enzymatic reac-tions apply a unique, self-developed

Exterior views.

Concludes on page 20.


FINALIST


enzyme to achieve high productivityand high purity. The hybrid processfor peptide production utilizes bothbio and chemical synthesis. Lyo-philization is applied for the bio pro-duction process.

A Closed Systemto Prevent

Cross-ContaminationFlexible processing and prevention ofcross-contamination are essential re-quirements for a multi-product andmulti-scale plant such as the NBP. Asa result, the plant features such inno-vations as closed disposable trays forlyophilization, a closed purificationprocess, a closed continuous solid-liq-uid separation system, and a uniquepowder feed system.

Interior view.

For flexible processing, mobile equip-ment has been adapted to meet therequirements of different products andproduction scales. Common utility sta-tions that can be conveniently con-nected to variously sized equipmentare made available to each productionroom. Elongated body fermenters andother vessels enable wide-ranging vol-umes of culture and products to bemanufactured. All of these contributeto cost reductions through the minimi-zation of space, piping, cable, valves,

and instruments.

Manufacturing Ex-ecution Systems(MES) and DigitalControl Systems(DCS) offer easilyconfigurable toolsfor operation andproduct changes,meeting the multi-product and multi-scale requirements.The DCS was de-veloped based onISA S88 for changesof recipe and con-trols operations. By

communicating with the DCS, the MEScontrols the manufacturing step andadopts a bar-code system to preventcross-connection of piping and errone-ous feed of raw material.

Reliability andCompliance

For improved reliability, the NBP isequipped with uninterruptible co-gen-erative electric power, e-mail warningtransfer system to mobile phones, anautomatic emergency stop system forearthquakes, Web cam monitoring, andIC card access control.

Plus, this world-class and criticallyimportant plant is distinguished byfull cGMP compliance (Impact Assess-ment, Risk Assessment and DesignQualification {DQ}), ultra fast trackproject execution, and in its designphase, 3-D CAD engineering as well asComputational Fluid Dynamics (CFD).Significant contributions to the phar-maceutical manufacturing industry arehighly anticipated to result in a stablesupply of bio bulk products while short-ening the period required for new drugdevelopment.

“Flexible processingand prevention of

cross-contaminationare essential

requirements for amulti-product

and multi-scale plantsuch as the NBP.”

Exterior view.

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FINALIST


Janssen Pharmaceutica

Small Volume Area Produces Big Results

In 2003, the Janssen Pharmaceutica chemical productionsite in Geel, Belgium installed a new powder-handlinginstallation aptly named the Small Volume Area (SVA) –

Powder Unit. This Small Volume Area (SVA), the first of itskind within Janssen’s parent company, Johnson & Johnson,is a unique combination of state-of-the-art micronizing equip-ment and high-tech separation of the working environmentusing isolators (glove boxes).

The installationis to be used toobtain the cor-rect particle sizedistribution forthe most potentdrugs manufac-tured at the site.It now allows forgreater protec-tion of product,

enhanced worker safety, and a boost in production efficiencyfor 30 different chemical products.

The Need for Increased ProductionJanssen’s Geel chemical production plant plays a crucial rolein producing Active Pharmaceutical Ingredients (APIs) forlife-changing medicines to treat mental illness, allergies,women’s health issues, and gastrointesti-nal disorders. Significantly, the SVA pro-cess increases production to more than adozen tons of product each year - equiva-lent to hundreds of millions of patienttreatments annually.

Fully-Contained ProcessThe SVA is part of a high-containmentproduction chain, which consists of fourseparate state-of-the-art production in-stallations for weighing, production, pow-der handling, and material-cleaning. Con-sistent with the containment technology,these installations are fully enclosed,which substantially enhances quality andsafety.

Together, these installations constitute an isolated process-ing chain. Transport between the various installations isperformed by means of special sealed drums which can beopened only after they are coupled to an isolator.

Every stage is executed in a fully closed way throughspecially designed equipment integrated in isolator tech-nology (glove boxes). New design standards were employeddue to ergonomic considerations, equipment size, and pres-

PROJECT: Small Volume Area(SVA) – PowderUnit

LOCATION: Geel, Belgium

DESIGN-BUILDPARTNER: Janssen

PharmaceuticaChemicalProductionEngineering

Continued on page 24.Aerial view.

Exterior view.

We aim for the highest quality in thedevelopment, production and mar-keting of drugs. We want to achievethis with the greatest possible careto the well-being of our employees,our fellow citizens and our environ-ment.

The best possible health for asmany people as possible is our ob-jective. And our responsibilities donot stop at the company gate. Weare fully aware that a company likeours is helping to shape the futureof the world. That is the challengefor everyone in our company – achallenge that we gladly take uponourselves day after day.

Better drugs for a better world

Turnhoutseweg 30, B-2340 Beerse, Belgium


FINALIST

sure safety of placing a pneumatic transport system into theisolators.

Testing of mock-up isolators was essential to project successdue to the many operations that need to be performed withthe equipment such as assembly and dismantling for clean-ing. A single, unworkable operation would render the entireinstallation unusable.

Janssen Pharmaceutica Chemical Production Engineering,the lead design firm on the project, championed the build ofthe detailed mock-ups, using 3-D software with walk-throughmode, and involved operators, technicians, engineers andmanagement from the start of the project, allowing for thecreation of an ergonomically-designed installation that saved$300,000 with initial process flow reviews.

Installations and Technology PlatformsSpray DryerDuring the spray drying process, a suspension is sprayed athigh pressure in a drying chamber with a warm nitrogenstream. Rapid evaporation of the solvent results in a powder-particle form, making uptake in the human body easier forsome products. This installation was built with patient friend-liness in mind and resulted in enabling patients taking AIDSinhibitors to cut their dose from 16 pills per day down to onlytwo pills per day.

Bromination and HydrogenationTwo separate installations are available for these processes,and both have processes in place to meet safety standards.Geel is the only site within J&J with such a combination ofinstallations.

Preparative Separations Techniques (PST)In some cases, chromatography is the only way to separate twohighly similar substances, and at the facility in Geel, this isaccomplished on a production scale with the PST installation.This is capable of separating 2,100 kg of material in 2.5 days.

Meeting Goals forProduct Quality and Safety

Overall, the facility results in a positive impact on productquality and safety.

“New design standardswere employed

due to ergonomic considerations,equipment size, and

pressure safety of placinga pneumatic transport system

into the isolators.”

CallforEntries

It's not too early to begin planningyour submission for 2007... Don't letyour company pass up thisoutstanding opportunity to showcaseyour new or renovated facility!

For complete information about theAwards program and submissionprocedures, contact Scott Ludlum,ISPE Director of Business Initiativesby tel: +1-813-739-2284 or by e-mail: [email protected]. You can alsovisit: www.facilityoftheyear.org

SAFETY BY CONTAINMENT

SKAN AG • Postfach • 4009 Basel • Switzerland • Phone +41 61 485 44 44 • [email protected] • www.skan.ch

ISOLATORS AND GLOVE BOXESFOR ASEPTIC AND POTENT APPLICATION


FINALIST


Quality: Protection of the ProductThe SVA installation complies with EU Grade C (ISO 14644-1 Class 7 (particles > 0.5 µm) + microbial requirements),which allows for the handling of intermediate products forparenteral use. It must remain completely sanitizable throughClean-In-Place (CIP) after each campaign. Sterility is notrequired.

Safety: Protection of the OperatorFor the first time, Personal Protective Equipment (PPE) is nolonger necessary to protect operators from exposure to highpotent APIs. The SVA itself is shielded. The installation hasa Design Exposure Limit (DEL) of 50 nanogram/m³. The eighthour average ambient concentration of the product does notexceed this value.

A Heritage of InnovationFor more than 30 years, the Janssen Pharmaceutica site inGeel has played a crucial role within Johnson & Johnson inproducing APIs for medicines – and the plant now suppliesabout two-thirds of worldwide chemical production for

Interior view.

Johnson & Johnson’s pharmaceutical sector. The SVA in-stallation is the latest example of the company’s ongoingcommitment to invest in new technological innovations toensure efficient, safe, and cost-effective delivery of high-quality medicines.

BnS Engineering and Foster Wheeler congratulate Janssen Pharmaceutica.

Having worked closely with Janssen, we are proud to be associated with

the innovative small volume powder unit.

• Master Planning

• Concept Design

• Basic Design

• Engineering

• Construction

• Commissioning

• Validation

[email protected] www.bns.be [email protected] www.fwc.com


FINALIST


Wyeth Pharmaceuticals

Biotechnology Excellence in a King-Sized Package

Which comes first, the manufac-turing processes or the infra-structure to house and oper-

ate the processes? In planning con-struction for its new biopharmaceuticalcampus in Grange Castle, Ireland,Wyeth Pharmaceuticals consideredboth from the start. The result is thelargest fully-integrated facility everbuilt in a single phase.

One of a Kind CampusWyeth's new state-of-the-art Bio-Pharma Campus at Grange Castle isnot just another biotechnology facil-ity. The campus is an innovative ap-proach to industrial facility design.Rather than introduce another bio-technology plant, Wyeth focused ondeveloping a homogenous campus en-vironment where core functions drivemanufacturing and material handling.Also, the dramatic use of curved stonefacades and generous glass offer abuilding to the local community thatmany would be proud to live beside, indirect contrast to a normal low-keyindustrial complex.

The integrated campus includes threeseparate facilities: a Drug Develop-ment Facility to coordinate and vali-date the technologies and proceduresrequired to migrate products and pro-cesses from the laboratory to the com-mercial production stage; a multi-prod-uct Drug Substance Facility for mediapreparation, fermentation, and purifi-cation stages of manufacture; and aFinished Product Facility for formula-tion, vial preparation, filling, capping,and inspection.

PROJECT: Wyeth BioPharma Campus atGrange Castle

LOCATION: Grange Castle, Ireland

DESIGN-BUILDPARTNER: Jacobs Lend Lease - JLL (a joint

venture between Jacobs andBovis Lend Lease)

Concludes on page 28.Exterior view.


FINALIST


Achieving ThroughPartnering

In late 1999, Wyeth had a need toquickly expand production capacity forEnbrel®, a drug used to treat rheuma-toid arthritis, and Prevnar®, a vaccinethat helps prevent meningitis and bac-teremia in children. Motivated by pa-tient need - and the little time patientshave to wait for these life-saving drugs- Wyeth envisioned the construction ofa fully-integrated biopharmaceuticalfacility that would allow for flexibilityin processing and expandability for fu-ture products.

The big question was, “How do youdesign and build a new 90 acre,1,000,000 sq. ft., facility that will housemore than 1,100 employees and de-liver product on schedule?”

Partnering was the answer. Wyeth fos-tered close relationships with govern-ment agencies, design companies, andvendors to implement an alliance con-tractor framework for construction ac-tivities. This allowed Wyeth to easilydirect delivery speed and constructionquality. The company also mobilizedan Integrated Commissioning and Vali-

dation (ICV) organization, to unite allstakeholders under one organizationwith the sole purpose of qualifying thefacility. Equally significant were thetremendously high project safety stan-dards which resulted in Wyeth postingan overall injury rate notably lowerthan the national manufacturing aver-age both in construction and opera-tions.

Focused on project delivery, designteams conducted interactive sessionsthat included operators, technologists,designers, equipment suppliers, andconstruction organizations. Projectteams targeted solutions to ensure suc-cessful operational start. For example,at an early stage in the drug substancefacility design, the team decided toimplement a closed process system topermit sanitization of equipment andpiping without the need to re-open thesystem. This allowed for the protectionof product quality and a lowered roomclassification.

For effective start-up, the operationsteam, engineers, construction teams,and contractors were co-located on thesite. Support functions and facilities

were co-located as much as possible.The ICV team was initially co-locatedwith construction, and when the op-erations’ staff took up residence in thebuildings, ICV was co-located with op-erations and site engineering staff toallow for a continuous flow of knowl-edge transfer and for new staff to be-come quickly immersed in the project.Material flow was enhanced both fromarea to area by use of wide enclosedcorridors and in manufacturing by theuse of closed loop piping and transfersystems.

A Facilityfor the Long Haul

With its new BioPharma Campus en-gineered by Jacobs Lend Lease (JLL),Wyeth has achieved much more thanthe distinction of owning and operat-ing one of the world’s largest biotech-nology facilities. By combining estab-lished industry best practices thatoptimize manufacturing with team-oriented project delivery methods thatdrive collaboration and overall speedto market, Wyeth has delivered atrue world-class facility that will servethe company well into the comingdecades.

Interior view.

“Equally significantwere the tremendously

high project safetystandards which resulted

in Wyeth posting anoverall injury rate

notably lowerthan the national

manufacturing averageboth in construction

and operations.”

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Judging Panel Chair Interview

An Interview with Peter BigelowFacility of the Year Judging Panel Chair

Peter Bigelow, Senior Vice Presi-dent, Consumer HealthcareManufacturing for Wyeth, hasserved as the Judging Panel Chairof the Facility of the Year Award(FOYA) for the past two years.This year’s competition marks hislast year as Chair.

In this interview, Peter givesus a behind-the-scenes look at thejudging process and shares hisviews on how the award plays an

important role in advancing the pharmaceutical manufactur-ing industry.

Q Tell us about your experiences and what significantcontributions the competition has made to the pharma-

ceutical manufacturing industry.

A The Facility of the Year Award competition has allowedus to showcase exceptional work that’s being done by

the engineering community in our industry. Typically, manyof these projects would be completed without a forum forpeople to find out about them. This competition has enabledus – at least for some of the major and significant projects inour industry – to provide a broader forum for individuals tosee and understand the innovations taking place in facilitydesign and engineering.

Before FOYA, this type of information would be obtainedthrough less timely and less objective methods, such as wordof mouth, presentations from service providers, magazinearticles, or through facility tours conducted by some of thelocal ISPE Chapters and Affiliates.

It’s important to note that this competition not onlyhighlights how a certain facility was designed or built on timeand under budget, it allows us to identify and showcase someof the best practices utilized in the industry today. We’vefound that some of these best practices come from some of thesmaller projects and not only by “Big Pharma.”

Q Can you tell us about the judging process?

A Although it sounds like it would be grueling, and thereis a lot of work and negotiating involved, the judging

process is a wonderful and rewarding experience.I think that you always want to seek more information

than you have. So, being limited to the information in eachentry can be a stumbling block to some extent. There were

very few questions as to whether some facilities were quali-fied, because the companies that submitted facilities did anexcellent job showcasing their projects within the awardcriteria. The integrity of the entries really reflects the integrityin this industry.

Because of the high quality of all the presentations andfacilities, we had to make some very difficult decisions,although I think we reached consensus pretty efficiently. Inmost cases, the differentiation between who’s a finalist ver-sus who isn’t, and who’s the overall winner, versus who isn’t,is fairly small. When it came to making the final decisions,the tie-breaker was innovation, whether in the form of a newand important process, or in the design or construction, or inthe approach of one of the major objectives of the project.Another key factor was overall execution of the project.

Q What are some of the notable technological and innova-tive advances you are seeing in facility design and

construction and how are these advances changing the wayfacilities are built and pharmaceuticals are produced?

A We are seeing a lot of modularization. That is probablythe single most significant technological advance that

comes through. The advantages of modularization are theflexibility and the ability to move quickly.

We’re seeing a lot of very interesting and innovativeprocessing changes that are more efficient, have higheryields, and are more compliant in respect to Good Manufac-turing Practices (GMP). The industry is becoming morehighly automated, and with that increased level of efficiency,brings a higher level of compliance.

An example of innovation would be the technology em-ployed by Biolex Therapeutics. Instead of using traditionalcell culture methods, the Biolex manufacturing process em-ploys a unique expression system. We found that to be a veryintriguing new innovation in biotechnology.

In regard to the use of new technology in the entries, we didsee some examples of islands of Process Analytical Technol-ogy (PAT), but none of the facilities have implemented PATto the extent that is anticipated in the future. However, Ithink that in the next few years, PAT will yield a new kind ofera in our industry.

Q Why is it so important for the benefit of the industry forcompanies with eligible facilities to submit an entry?

A Let me emphasize that in the past two years, each andevery facility that was entered into the competition was

exceptional and worthy of some kind of an award. This


Judging Panel Chair Interview

competition is not about winners and losers. All entries werewinners and we selected the best from a group of winners.Therefore, no one should feel embarrassment or any kind ofnegativity if they are not selected as a finalist.

As I noted earlier, it was very difficult and a little frustrat-ing for the judges because sometimes there was not a lot ofdifferentiation between entries and finalists.

Entering this competition is a tough decision for eachindividual company. Coming from one of those companiesmyself, I understand that it is a tough balance betweenprotecting science, investment, and good ideas from competi-tors, and showcasing new and innovative technologies. Butentering this competition accelerates the ability for all com-panies to employ some of the good work, best practices, andfacility and process innovation that is out there. We can makeimprovements in quality and costs quicker and more effec-tively. These improvements are a benefit to all of us.

Q Understanding the submission criteria were not rankedor weighted, which of the criteria did the judges seem to

be most impressed with?

A The judges seemed to be most impressed with projectuniqueness and innovation. Advances in facility design

technology and excellence in execution were also important.The ability to bring the project in on time, execute it well, andfollow good methodology to get it done also seemed to beimportant criteria.

Q What messages, best practices, and lessons learned canthe pharmaceutical manufacturing industry take away

from the competition?

A One message or lesson learned is that good projectexecution can be done in any part of the world. Innova-

tive and complex technologies can be employed in any part ofthe world. The industry is truly global. We are producingfacilities of similar quality. The way we employ technologiesand techniques, and the way we carry out project execution isvery similar in every part of the world. The global nature ofthe pharmaceutical industry is truly reflected in this compe-tition.

Another message is that our industry is a complicatedbusiness and there is a lot of competition. Therefore, pro-cesses and facilities are getting more complicated, invest-ments are huge at times, and the demands of the business arevery significant around facility and process design.

Certainly, another message is that at the forefront of everyproject is the impact and improvement of quality. Everybodyis talking about quality and everybody is trying to makequantum leap improvements in quality.

Q It’s possible that state-of-the-art facilities could beassociated with large, grandiose, and expensive. Is this

accurate based on your experiences reviewing submissionsfor the competition?

A There was a mix of large-, small- and medium-sizedprojects. I think the committee did a good job of not

being overly enamored with a project because it was large,and tried to look at a project’s innovation, technology, andoverall contributions to the industry.

State-of-the-art does not necessarily mean that it has to bebig, expensive, and grandiose. And, we’re seeing state-of-the-art in every project, regardless of size.

I think “Big Pharma” is stuck in a paradigm when it comesto facility design and has trouble being creative, innovative,and flexible. In “Big Pharma,” we tend to design somethingthe way the last project was designed and try to makeincremental improvements. Some of the smaller facilitiesand companies – because they have a small budget and fewerresources – take a totally different approach. Sometimes thatapproach, which is more agile and creative, can yield excel-lent results.

I think that “Big Pharma” could learn from some of thesesmaller projects how to be more flexible and to be morefocused on the real needs of the business.

Q What final comments do you have about the Facility ofthe Year Award competition and its impact on the

industry?

A Personally, I think ISPE has made phenomenal con-tributions to the industry. ISPE brings people together

from around the world – from large to small countries, fromsuppliers to equipment sellers – for an open, honest, anduseful forum for exchanging information, for becoming edu-cated, and for finding out about new products. ISPE hashelped accelerate a lot of good engineering in our industry.These facilities are real concrete examples of what ISPE talksabout all the time in its guides and courses.

It’s important for everyone in the industry to learn fromeach other, to understand what works and what doesn’t, andto employ innovation and good solid technologies. It’s a verygood way to showcase important things that are taking placein our industry. All the competition sponsors, ISPE, Pharma-ceutical Processing magazine and Interphex, have similargoals, and this competition is a real complement to whatthey’re trying to accomplish.

The judges we’ve been able to assemble have done a greatjob. They’ve been committed to this competition, had greatthoughts, and used their many years of experience to collabo-rate and make good decisions. So, I really appreciate thecommittee’s efforts.

From a personal point of view, this has been a veryrewarding experience for me. It’s given me an insightfulglimpse of the industry. And, it’s made me feel really goodabout where we’re headed as an industry.

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