focus issue6

8/2/2019 Focus Issue6

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focusFOSTER WHEELER S PHARMACEUTICALS BUSINESS MAGAZINE

ISSUE 6

Focus on containment


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blished by

ter Wheeler

nfield Park

ading

kshire RG2 9FW

w.fwc.com

naging Editors

olyn Greenhalgh

ector, Corporate Communications

lobal Marketing

0118 913 2494

[email protected]

queline Hogarty

rketing Consultant

0118 913 2167

[email protected]

duced by FW Graphics Group

oster Wheeler

FOCUS ON CONTAINMENT

As a change from the norm, this issue of focus is given over to a single topic.

The protection of operators and the environment has always been a priority forthe pharmaceutical industry. The production of active materials in smallerquantities with much higher potency is driving an increasing number ofmanufacturers of bulk drug substances and final dosage forms to examine their

containment options. The increasingly risk-based regulatory framework and developmentsin containment technology are driving changes to the design and operation ofcontainment devices.

At Foster Wheeler we have gained considerable cutting-edge, practical experiencein devising and supplying containment solutions, to the point where we have beenselected as global containment consultants by one of our key multinational customers.

As part of our ongoing quality improvement program we recently held an informationexchange forum on containment to which we invited a number of clients, to share ourjoint experiences based on real-life case studies and a wide range of projects. Thecontents of this focus issue are based on that event, an idea that the participants activelyencouraged us to repeat in other technical areas.

Clive MullinsGlobal business director

The Containment Forum held in Milano was a very valuable experience.

Bringing together industry expertise from both engineering and operating companies inan informal setting to share non-proprietary knowledge and experiences allowed foropen discussion and debate as to good engineering practices relative to containmentsystem design.

I believe all involved gained some knowledge which will be applied to the improvementof future installations.

Paul Richards

Project & technology engineerPfizer Global Research and Development


3/16focus

setting the scene

Why is containment important?When considering containment there are multiple

drivers. The mix of critical factors will change

application-by-application, and the solutions will

vary accordingly. This leads to a very complex

subject and Paul Richards of Pfizer addresses

this range of solutions on page 9. Typically,

drivers will include operational hygiene for

operator protection, plant safety, product

quality, reduced environmental impact, and

operational improvement.

The operational health impacts on the operator

can be very serious. The use of personal

protective equipment has been shown to be

poorly effective in practice and its use for routine

operations has been discouraged by regulation.

All of this drives us to ensure better protection

for the operator. Pam Davison, in describing

GSKs forward strategy, addresses this area

on page 5.

Safety is, of course, dominant, for example in

handling materials in an inert environment. Theprime interest of the pharmaceutical product

regulators is patient safety, via the quality of the

medicinal product, and containment has to

prevent contamination or cross-contamination

of this product. As well as the internal plant

environment we are interested in preventing

material escaping to the external environment.

For some compounds, operator health may not

be an issue but potentially there could be

significant external environmental impact.

Recent changesPharmaceutical companies tend to specialise in certain therapeutic

areas, and the activity of their compounds reflects that. We see the

need to handle increasingly active compounds. We also see new

guidance, for example for cytotoxics, and the need to transfer

techniques from other industries such as the nuclear industry.

The pharmaceutical industry is now prepared to learn to SWIPE,

(Steal With Integrity and PridE) from other industries. Huw Thomas

describes what others are doing in dose form manufacture,

page 10. David Ainsworth covers the need to treat the

commissioning and qualification of facilities for nanogram

containment differently on page 11.

We are also seeing production of smaller quantities of materials, partly

due to their activity, and partly due to demand. This is changing the

associated method of containment and is addressed in

Nanocontainment and Small Scale Manufacture by Marco

Mascarenhas on page 3.

We are seeing an increase in the need to contain not only powders but

also aerosols potentially generated in liquid filling. Germana Molinari

gives a review of fill-finish design on page 7, and David Ainsworth

looks at a case study at a Janssen highly potent powder handling

unit (Facility of the Year Finalist 2006) on page 8.

Other changes involve increasing use of new solutions such as flexible

plastic, and increased use of gloveboxes. Huw Thomas, page 6, and

Emilio Moia, page 4, address these two areas respectively.

The use of risk assessments in many areas of life has become an

everyday subject. In the pharmaceutical industry they are embodied in

much guidance, now reinforced by ICH Q9. Their use in containment

occurs both at macro and micro levels and John Nichols discusses

this in an article on hierarchy and risk-based approaches on page 2.

What is

containment?If an overall manufacturing facility consists of three components pharmaceutical material, personnel, and the environment surrounding

them containment is the isolation of the first of these components from

the other two. ISPE

A KEY TECHNOLOGY AREA IN THE SPOTLIGHT


4/16

An holistic approachThe containment chapter of the draft ISPE BPC Baseline

Guide, to be issued in 2007, recommends

a similar holistic approach to that adopted for HSE, following the steps below in sequential order to

alleviate an exposure potential wherever possible:

Selection of containment elementsValues for the containment obtainable under typical operating conditions for an average material with

good operating practice (as illustrated on the enclosed reference card) can be used as guidance for

potential protection. However, all factors should be taken into account in selecting equipment for

a specific application.

There is potential for improving the performance of standard equipment by adding additional layers

of protection, such as illustrated on the card by a downflow booth with several typical upgrades.

Risk assessmentRisk assessment using a variety of tools is a widely-used technique. With the issue of ICH Q9, andthe ISPE RiskMAPP initiative, its use in pharmaceutical containment has been reinforced. Ranking the

exposure potential enables a better choice of an appropriate methodology for containment equipment

selection, taking into account particular circumstances.

Foster Wheeler has developed a method for assessing the risk from widely different operations and

has used it for a number of projects to identify highest-risk operations and to prioritise upgrade work.

focus

holisticviewTHE HIERARCHICAL APPROACH TO CONTAINMENT

Successful containment requires an holistic approach:development of the correct strategy, selection ofcontainment elements by their capability for typical

operations and a risk assessment technique for rankingthe exposure potential.

ISPE Baseline Approach:Hierarchy of Containment

Modify process to remove hazard

Sealed equipment and connections

Localized containment devices

Contain in the facility

Use of procedures

Eliminate

Reduce

Isolate

Contain

PPE/Discipline

JOHN NICHOLS

John NicholsGlobal technology director

HSE Approach


5/16focus

nano-containmentEXTREME POTENCY AT A SMALL SCALE

Firstly, the increasing activity or potency of active

pharmaceutical ingredients for certain therapeutic areas

has warranted some materials being given an occupationalexposure level (OEL) of the order of 5-10 nanogram/m3

(plutonium is 0.1 nanogram/m3).

Secondly, some compounds are being manufactured in ever-

decreasing quantities, with some annual production quantities

of less than 1 kg, and we have even seen an instance of annual

production of about 0.1 kg.

These trends clearly impact on the design of pharmaceutical

facilities and equipment, and especially containment.

Established technology uses glovebox isolators with

rapid transfer ports and measures to reduce the

internal challenge to achieve the required containment.

Glovebox isolators are the chosen solution for small-scale nanogram operation and some standard units

are available from suppliers. Establishing the right

technology is driven by analysis using risk

assessment, and by custom and practice.

A recent project executed by Foster Wheeler for

a cytotoxic API involved the whole non-aseptic

cytotoxic production - including weighing/dispensing,

solution preparation, reaction, crystallization, filtering,

drying and weighing/filling - taking place inside one

five-chambered isolator.

Achieving 1-10 nanogram/m3

is highly demanding,and it should be appreciated that the glovebox

isolation technology for this level of containment is different

from that required to achieve microgram containment.

With continuing increased potency of pharmaceuticals, and

the prospect of manufacture of smaller quantities for responder

groups and so on, we see this type of facility becoming

more common.

Two significant trends are impacting themanufacture of active drug substances. These

trends are delivering some exciting innovations inglovebox isolators, plug and play concepts, processinterlinking, secondary containment and control.

MARCO MASCARENHAS

Marco Mascarenhas

Manager, bulk pharmaceuticals


6/16focus

Continuous development, innovation anda stringent attention to detail in design andmanufacture, maintains our product portfolio

at the cutting edge of technology.

isolatorsTHE DRIVE FOR INNOVATION

Steril, Foster Wheelers manufacturing division, designs and manufactures

a comprehensive range of vertical and horizontal laminar flow benches,

bio-safety cabinets and isolators for powder containment.

This is done in strict compliance with the exacting standards and design

guidance for containment which include:

ISO 14644-7: Separative devices (clean air hoods, gloveboxes,

isolators, etc)

ISO 10648-1: Containment enclosures

Part 1: design principles

ISO 10648-2: Containment enclosures

Part 2: classification

AGS-G001-1998: Guideline for gloveboxes

EN 12469: Performance criteria for microbiological

safety cabinets

In addition, a continuous research and development programme maintains

Sterils equipment at the forefront of LAF and containment technology.

Results from this development programme include:

An innovative isolator exhaust system that, in the event of an accident,

has a zero transition time to safe operation. This development has been

operating in a high potency drug facility in Italy since 2005.

Containment solutions for gaseous decontamination involving products

that are effective against biological agents but which can, after use, be

rendered harmless.

EMILIO MOIA

Emilio Moia

Manager contamination control

& containment

Pharma i

Both of these developments were covered in more depth in the

previous issue of focus which can be found at:http://www.fwc.com/publications/focus.cfm


7/16focus

occupationalhealthAN OPERATIONAL PERSPECTIVE

Adverse health effects related to chemical agents canseriously affect a persons quality of life and in somecases be life-threatening. Of these, allergic and dermatitic

reactions form a significant proportion of reportableoccupational diseases. Clearly the industry has a dutyof care to protect workers from exposure to such agents.

A study looking at ten pharmaceuticalmanufacturing sites owned by different

companies, showed that of the 211 subjects

tested, 145 (69%) had leaking respirators.

The study also showed no correlation

between the effectiveness of the respiratory

protective equipment and the frequency of

use, experience or training. In addition it can

be shown that if a respirator is only effective,

say, even 98% of the time, it can fail to meet

the desired application requirements.

GSK has set itself a challenge to have 80%

of its unit operations respirator-free by 2010.

Further, when matching engineered controlsolutions to problems it is necessary to

understand that it is not just a direct

relationship to the Occupational Exposure

Level (OEL).

Factors such as scale, dustiness, process

energy, and API content can alter the most

applicable control strategy for a given OEL.

GSKs integrated strategic approach

includes documented established solutions,

communities for engineers and hygienists,

tracking performance, hygienist networking

and training, a behaviours program, engineer

training, and established partnershipswith suppliers.

focus

Pam Davison

Technical directorGlaxoSmithKline

PAM DAVISON


8/16focus

flexiblecontainmentA TABLET MANUFACTURING CASE STUDY

Disposable systems can provide efficient, cost-effective containment inthe right application. They are very adaptable and can accommodatea wide range of applications, but are not the best solution for all

applications. Taking a wider viewpoint, using the layered approach isa good underlying principle for containment selection and design.

A recent project involved the specification of

a containment upgrade to allow manufacture

of a particular higher potency product in anexisting small-scale tablet manufacturing facility

with granulator capacity of 400 litres. The

operator exposure limit for the compound being

handled was 10g/m3, and we needed to

implement short-term upgrades quickly before

the next campaign, with minimum disruption to

manufacturing operations.

Flexible, disposable containment was the key

to this project, and it had to be designed,

made, tested, modified, installed and the

operators trained in just thirty days!

The results of personnel monitoring (outside

air suits) showed exposure was reduced by

up to 1000-fold by the use of flexible barrier

containment. Although exposure was still

affected by operator action, it was less so

than with the use of personal protective

equipment alone.

In addition to the flexible glovebags, use was

made of Spraylat

floor covering to trap any

potential surface contamination. There was a

significant reduction in surface contamination,

leading to a 20-fold reduction in room cleaning

times. The disposable Spraylat

floor waspeeled up, thrown away, and the surface

swabs were clean.

Future use of disposable containment may

include the design of granulator and fluid bed

drying glovebags, modified and extended to

the other granulation sites in the facility.

Longer-term engineering improvements need

to be made to areas not suitable for flexible

containment, for example through-floor feeders,

automated bin charging and discharging.

Some useful containment figures:

One sugar crystal ~ 1000 gmOne grain of sand ~ 100 gm

100 particles of pollen ~ 10 gmHousehold dust ~ 1000 gm/m3

Typical airborne concentrations from open handling:

Dispensing 1,000 - 10,000 g/m3

Manual charging 10,000 - 50,000 g/m3

Granulation (scraping) 10,000 - 50,000 g/m3

Drying (open transfer) 5,000 - 100,000 g/m3

Compression 10 - 300 g/m3

Disposable / Flexible Containment Principles

OPERATORPROTECTION ONLY

AIRBORNE CONTAMINATIONCONTROL BEST

POOR

SURFACE CONTAMINATIONCONTROL BEST

IMPLIED INHERENT

FLEXIBILITYERGONOMIC FLEXIBILITY

CAREFUL

DESIGNREQUIRED

HUW THOMAS

Huw Thomas

nior pharmaceutical

engineer


9/16focus

fill-finishTHE CONTAINMENT SOLUTION FOR YOUR OPERATION

In the absence of a one size fits all solution to thecontainment of fill finish operations, a logical approach

to the design of effective protection is required. Key tosuccess is the correct combination of working areaconfinement and personnel gowning.

Previous solutions often relied on personal

protective equipment (PPE) together with

contained rooms or departments to protect the

environment. Now, more and more, the approach

is to use primary containment at the very

source of product exposure, using secondarycontainment as a back up solution and PPE

as an emergency/short-term intervention

protective device.

The essential first step is identification of the

critical operations, typically:

The range of containment devices applicable to

the different operations is wide and includes:

contained connection - split valve, high

containment valve, rapid transfer port,

continuous liner

glovebox isolator

closed restricted access barrier system

(C-RABS)

Crucial is the awareness that there are no

universal solutions applicable to every situation.The selection of the proper containment solution

should include an analysis of the key features of

the operation to be contained, typically:

product potency - low, medium, high

product form - liquid or solid

product diffusion capability - aerosol

generation, powder spread

activity duration - occasional or shift-based

product exposure - open or closed activity

aseptic processing requirements - meeting

HSE and GMP requirements

product potency issue or only cross-contamination prevention

Three possible indicative decision trees are below:

Injectables Facility

Dispensing

Formulation

Filling

Lyos unloading

Oral Solid Dosage Facility

Dispensing

Product transfer

Tabletting/capsule filling

Blistering/bottle filling

Working area protection LIQUID

Potency

StandardApproach

C-RABS(only for cross-contamination)

C-RABS(for personnel safety)

Containment

Isolator

Medium

High

Very High

Low

Aerosol?

N

Y

HP : no PPE use

Working area protection SOLID

C-RABS(only for cross-contamination)

C-RABS(for personnel safety)

ContainmentIsolator

Medium

High

Very High

Low

Potency

HP : no PPE use

Verypowdery?

N

Y

Y

N

Almost notpowdery?

Product Transfer SOLID

Medium

Very High

Low

Potency

HP : no PPE use

Open process allowed orClosed process with butterfly valves

Closed processwith standard split valves

Tight closed process withhigh containment valves

Tight closed process withRTP parts and glove box

High

GERMANA MOLINARI

Germana MolinariSenior finishing &

formulation engineer


10/16focus

highlyactivepowdersCASE STUDY OF AN AWARD WINNING PROJECT

Janssens major primary pharmaceutical manufacturingsite at Geel in Belgium produces thousands of tonnes peryear of active pharmaceuticals and intermediates. The site

has almost 100 reactors and manufactures a wide range ofmaterials of varying levels of potency. The most potent

products OEL of less than 5 micrograms/m3 means veryhigh containment requirements.

Recently, Foster Wheeler and local Belgian partner BnS

worked together to deliver a high containment solids handling

facility. The process involved delumping, milling, sieving,

homogenizing and pack-off and all of these operations were

designed to be undertaken within a series of bespoke

gloveboxes. Glovebox design had to take full account of the

processing needs and also enable full disassembly and

cleaning of the solids processing equipment.

Complex ergonomic mock-up models of the process

equipment were developed to ensure that the design on

paper was practical and enabled all of the required

operations to be undertaken by an operator working via

gloves. Heavy equipment was mounted either on hingesor slides, flexible connections were needed in the powder

transport piping system and full nitrogen inertion was

necessary to prevent explosions!

The design containment level of 50 nanograms/m3 was

achieved, the project was completed from concept to process

start-up in two years and the degree of innovation achieved

was recognized by the project being selected as a finalist in

the prestigious Facility of the Year Awards in 2006.

Foster Wheeler is delighted to announce that the General Technical Services Department of JanssenPharmaceutica NV has awarded its annual Quality Certificate to Foster Wheeler, in recognition of its

contribution to the development of the concept study for the recently announced Chemical Development

Pilot Plant (CDPP).

Foster Wheeler scored the highest possible rating, AA, in this award, which is given to the best performing

contractor at Janssens Geel and Beerse sites in Belgium.

Foster Wheeler is continuing to support Janssen with the BOD-B (FEED) phase of the project.

DAVID AINSWORTH

David AinsworthPrincipal consultant

Quality

Award


11/16focus

bulkchemicalmanufactureA GUIDE TO CONTAINMENT OPTIONS IN API PLANTS

There are many engineering control options forcontainment. What option is most suitable for yourapplication? What is the range of performance

expected with various containment solutions?Who are the primary vendors? And what are thebudgetary costs? Question, questions .

But a useful starting point is: what are we trying toachieve? If we consider that 1 granule of sugar is

about 3 milligrams, then a containment level of

3 g/m3 is like dispersing 1/1000th of 1 granule of

sugar in 1m3 of air - pretty exacting stuff!

In API plants, the movement of materials, supplies,

tools, wastes, and recovery systems into and out of

the contained environment is the key to successful

containment. The performance of an isolator is only

as good as the transfer devices on the isolator.

There are many different transfer devices available

on the market, each with its own pros and cons.

A primary concern with split butterfly valves, forexample, is material on the faces of the valves

after undocking, and concerns with cleaning

extraction rings.

Some recommendations include:

Contain at the source

Avoid technique-dependent systems

Many containment technologies are

available and continue to evolve

Transfer system selection is a key to

successful containment

Design below the operator exposure limit

Consider ergonomics, cleaning, sampling,

waste, material compatibility

Provide redundancy/secondary containment

Engineer out the reliance on personal

protective equipment

And the golden rule is, there is no silver-

bullet containment solution!

focus

Paul Richards

Project & technology engineerPfizer

PAUL RICHARDS


12/16focus0

oralsolidsmanufactureSURVEY DEFINES BEST PRACTICE

BackgroundThe pharma company currently has

no OSD facility designed to handle

actives of


13/16focus 1

factoryacceptancetestsHIGH CONTAINMENT ISOLATOR CASE STUDY

Bearing in mind that a required containment level of less than5 nanograms/m3 is the equivalent of one grain of pollen in anaverage-sized living room, factory acceptance testing at such

levels can be pretty exacting.

To demonstrate the performance of a number

of high containment gloveboxes to be installed

in an existing primary pharmaceutical

manufacturing unit, Foster Wheeler went to

extraordinary lengths. Testing of the units

covered:

ergonomics - operations, controls and

sequences

documentation - GA, P&ID and materials

checks

lighting and noise level checks

surface finishes, cleanability and drainability

airflows, operating pressure and inertion

times

accuracy of instrumentation

connections to pressure systems

leak performance - pressure and vacuum

testing

containment performance - surrogate

material testing

In particular the containment performance

testing of each glovebox was stringent.

A surrogate material, Sodium Naproxen,

detectable at levels as low as 0.5 nanograms,

was used to mimic the actual operations that

would be conducted in each glovebox. The

surrogate test material was kept in double-

sealed containers inside a small storage room

(actually a garden shed bought locally!).

This was segregated from the rest of the

factory by a temporary polythene sheeted

antechamber to guard against inadvertently

contaminating the glovebox test environment.

Surrogate test material to be used in testing

each glovebox was loaded into sealedcontainers in this storage room; the

containers were then cleaned and passed

out of the room for further cleaning outside

the factory.

Once the containers were thoroughly clean

and free of any of the test material on the

outside, the container was double-bagged

and sealed and then brought back into the

facility for use in the glovebox testing area.

The container was docked onto the glovebox

in the test area and the surrogate material

introduced via rapid transfer port into theglovebox interior. Here a full cycle of the

required operations was conducted. During

this cycle of glovebox operations, both

airborne and surface samples were collected

from the surrounding environment.

The entire operation was undertaken on

three separate occasions to demonstrate

the effectiveness of the glovebox. At Foster

Wheeler, we really do roll up our sleeves

and get on with the job!

DAVID AINSWORTH

Photos from l to r: Store, Test Enclosure,

Preparing for Testing, Inside the Test Chamber.

David AinsworthPrincipal consultant


14/16

Secondary

General

Infrastructure

Validation

API

Biotech

R&D

Medical Devices

Category Key

focus2

fwpharmasuccessGLOBAL ROUND-UP OF RECENT WINS

We are very pleased to

work with Foster Wheeler

again and have every

confidence that our joint

teams will work together to

successfully complete this

phase of the project on

schedule. This will provide

a firm foundation upon

which to build for

subsequent phases

of the project.

We have been working

successfully with Foster

Wheeler since 2001

we are pleased with Foster

Wheelers professionalism,

responsiveness to our

needs and capability to

mobilise highly qualified

resources from its

European offices...

We have selected Foster

Wheeler for this challenging

project because of its ability

to make available skilled

resources from its various

operations centers, under

the management of Foster

Wheeler Milan.

The team has a very

proactive approach and

the team members are not

afraid to roll up their

sleeves. There are too

many names to mention

individually, but the whole

Alliance team has made

an outstanding contribution

to achieving our business

objectives.

Elsewhere, our clients continue to value the quality

of our teams and the facilities we design and build.

We continue to secure significant new pharma business

around the world, across the full range of technologies.


15/16

&

focus 13

John Nichols, pharmaceutical technology director, has been re-electedto the ISPE Board of Directors. This two-year appointment is Johnssecond, and is a significant achievement. John has contributed a greatdeal to ISPE. He works on a number of ISPE committees: theInternational and European Education Committees, Facility of the YearCommittee, Body of Knowledge Task Team and API Community of

Practice (CoP) and CoP Council. In 2003, John was a member of the ISPEs Facilityof the Year Task Team which received the Committee of the Year award. He alsoregularly chairs and speaks at ISPE conferences promoting Innovation in the Industry.

ISPE Congress, ViennaThe Annual European Congress wasattended by a large cross-section oftechnical specialists from across Europeand even beyond. John Nichols, ourglobal technology director, co-chaireda well-attended session which exploredhow to introduce continuous processing

into pharma facilities.

ISPE Annual MeetingOnce again, the ISPE Annual Meeting this year in Orlando, Florida attracteda large audience, as well as almost300 table-top exhibitors.

John Nichols was course organizer andchair for the seminar on ContinuousProcessing in the Real World.

Our presence in the exhibit hall (and inthe committee rooms), enabled us tomake contact with a large number ofkey clients who were attending.

Society of Chemical IndustryAt the SCIs Process DevelopmentSymposium in Cambridge, MarkDickson, senior process engineer,presented on Continuous Technology...when, how and why we shouldchange, highlighting the advantagesof continuous processing over

traditional batch operations for lowtonnage products.

ISPE BrusselsThe ISPE year ended at Brusselswhere Foster Wheeler had a significantpresence.

John Nichols participated in the sessionreporting on the latest update of the BulkPharmaceutical Chemicals Baseline

Guide, speaking on containment and

the activities of the API Communityof Practice.

Huw Thomas, senior pharmaceuticalengineer, contributed to the OralSolid Dosage session with a paperon containment.

Exhibitions

Conferences

ISPE Appointment

Come and meet us at:

ISPE Tampa Conference,

Florida

12-15 February

ISPE Copenhagen Classroom

Training, Denmark

26 February - 1 March

Bob Adamson, our pharmaceuticalcompliance manager, will be discussingtheApplication of Commissioning andQualification and Bob Davies, principalbiopharma consultant, will be lecturing onBiopharmaceutical Process Development.

ISPE Paris Conference,France

16-19 April

John Nichols will be chairing a session onnanotechnology, and Paul Frey, ourprincipal facilities consultant, will bepresenting a baseline approach tomodification of a WFI system.

Interphex, New York

24-26 April

Visit us at booth #143.

ISPE Washington Conference

Arlington, Virginia

4-7 June

ISPE Singapore Conference

10-12 June


16/16

Technical consult ancy

Feasibility studies

Concept design

Sit e select ion

Sit e master planning

Permitting

Environmental consultancy

Process simulat ion

Basic design

Detailed engineering

Proj ect management

ProcurementConst ruct ion management

Commissioning

Validation

Plant operation

Maintenance

Sit e remediation

the right people with a

can do attitude and the

commitment to deliver

PHARMACEUTICALS - BIOTECHNOLOGY - HEALTHCARE

[email protected]

www.fwc.com

focus issue6

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