www.geapharmasystems.com

GEA Pharma Systems

Aeromatic-Fielder

GEA Pharma Systems AG

PO Box 112, Hauptstrasse 145

CH-4416 Bubendorf, Switzerland

Tel: (CH) +41 61 936 36 36, (UK) +44 23 8026 7131

aeromatic-fielder@geapharmasystems.com

Central Know-How on a Global Scale

Based on a strong commitment to

research and development,

pharmaceutical technology centres in

Belgium, Denmark, Switzerland, the UK,

Singapore, and USA provide global

technical support and know-how to the

pharmaceutical industry. These centres

of excellence give customers access to a range of test facilities and expert

teams with technical and process know-how. Our teams work closely with

our customers to optimise processes and evaluate their products, enabling

them to achieve their process and production goals.

Contracting Profitable Experience

A world leader in supplying

pharmaceutical equipment, GEA Pharma

Systems offers manufacturers all over

the world the opportunity to enter into a

profitable partnership for development

and contract. GPS combine advanced in-

house technology with a thorough

understanding of the pharmaceutical industry to help customers maximize

their development results.

©GEAPharmaSystem

s2008

Specificationssubjecttochange

without

noticeAlltradem

arks

recognized

Fluid Bed Processor

Aeromatic-Fielder Technologies

GEA Pharma Systems

GEA Pharma Systems is world leader in providing

advanced processing solutions for solid dosage forms to

the pharmaceutical industry. Based on a dedication to

research and durable quality, GEA Pharma Systems

offers a wide range of solutions, from individual pieces

of equipment to complete integrated plants, by uniting

the state-of-the-art technologies of Aeromatic, Buck,

Collette, Courtoy, Fielder, Lyophil, Nica and Niro.

Product Know-How

Delivering the Right Solutions

Every Aeromatic-Fielder plant begins with the

customer’s desire to create a product that will

succeed in the market. In Aeromatic-Fielder, the

customer finds a partner who will assist him to meet

that goal. Our expertise includes technologies for

processing Active Pharmaceutical Ingredients using,

Blending, Granulating, Drying, Pelletizing and

Coating.

Plants Customised for Success

Every pharmaceutical plant and system from

Aeromatic-Fielder is a unique union of proven

technology and individual solutions. Based on

standard components, we supply plants for cGMP

production configured to meet the customer’s

specific requirements.

For more than forty years, Aeromatic-Fielder has supplied advancedsolids processing plants for blending, granulating, drying, pelletizingand coating to the pharmaceutical industry. This includes smallcapacity systems designed for R & D as well as industrial size plantsfor batch production of pharmaceutical compounds under cGMPconditions.

Our plant and process expertise is based on experience and R & D. With plants installed

around the world and literally thousands of tests performed, we have established a solid

base of expertise related to the needs of the pharmaceutical manufacturing industry.

A Partnership in Every Perspective

Working with Aeromatic-Fielder means entering a

solid partnership every step of the way, from process

testing and design to specification of the software

controlling your new plant. And our comprehensive

after sales program ensures that your return on

investment is optimised throughout the lifetime

of the plant.

Safety and the environment

For full compliance with national, local and in-house

regulations, Aeromatic-Fielder offers a range of

emission control options including solvent recovery

systems, outlet filters and full containment plants.

Equipment can be supplied to meet explosion-proof

and pressure shock standards as required.

Process Expertise

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• Drying • Granulating • Pelletizing • Coating

ProcessTechnologies

Drying

Warm air is blown through a perforated distributor to rapidly and gently

dry materials until the required residual moisture content is reached.

Moisture evaporated from the product is exhausted with the drying air.

Special features

Selection of air distributors

Short process time

Top Spray Granulator

The top spray granulator agglomerates finer particles into larger, free

flowing granulates in a one-pot process. Ingredients are mixed and pre-

heated by an upward flow of heated air. Granulation occurs by spraying

liquid into the fluidized powder. The granules are subsequently dried with

heated air. The top spray granulator can also be used for top spray coating,

layering from liquids, and instantizing.

Special features

One pot process

Selection of air distributors

Spray Dryer Granulator

The spray dryer granulator transforms suspensions or solutions into dry,

free-flowing, dustless granules. A suspension or solution of the substance

to be dried is sprayed onto warm air, simultaneously drying and

agglomerating the product. Batch or continuous discharge is available – in

the continuous mode, the product is discharged at a controlled rate to

maintain an optimum bed height

Special features

Compact unit

Easy scale-up

Batch or continuous discharge

For maximum process flexibility, Aeromatic-Fielder cansupply a single Fluid Bed unit or Multi-Processor™ systemwith interchangeable modules.

Drying

Top Spray

Granulator

Spray

Dryer

Granulator

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Built-in Versatility

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Precision-Granulator™

A rotating high velocity air stream is established in the central

agglomeration tube. Particles are picked up at the base of the tube

and accelerated by the air stream. The particles come into contact

with liquid droplets produced from the spray nozzle at the base of

the tube \ the relative velocity of air, liquid droplets and particles

are high so wetting is efficient and drying begins almost

immediately. Most of the feed material is in the outer “holding

area”, where the gas velocity is very low. Attrition is greatly

reduced. The gas humidity is also low in the holding area so the

material is dry not sticky. Individual particles may make repeated

cycles (typically from 10 to 1,000) through the tube, allowing very

large agglomerates to be built up.

Precision-Coater™

Used for smaller particles, such as powders, granules, seeds, crystals,

pellets, and small tablets. The product is coated and partially dried by

being blown upward through a central column with atomized liquid

and drying air. The material falls into the outer part of the container

where heated air completes the drying process. On reaching the air

distributor at the base of the module, the product flows again into

the central column for further coating. This process continues until

the specified degree of coating is obtained.

Special features

High spray rates for short processes

Highly controlled product movement

Minimal agglomeration or granulation

Precision

Granulator

Precision

Coater

Batch FluidTechnology

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Externalbag fitterNormally used inconjunction withthe particleretainer tocollect dust fromthe fluid bed incoatingapplications.

Quickclosing valve

HEPA filter

Open CycleDesign

Using proven standard components, Aeromatic-Fielder can supplyboth simplicity and flexibility in plant design. User-selected processmodules, filters, control systems and air preparation units combinein a system to meet process requirements exactly. This modularapproach ensures that qualification and validation procedures arekept to a minimum.

Through-the-wall installation

By positioning the support column at the back of the

fluid bed, a through-the-wall installation is achieved

which ensures that all the auxiliary equipment is

housed outside the process room. This greatly

simplifies compliance with GMP guidelines.

Solvent emission control

A range of open- and closed-cycle systems for

removing or recovering organic solvents is available.

Options include condensation, adsorption, thermal

oxidation and wet scrubbing.

Spraying systems

Nozzles, pumps and liquid preparation units are

supplied according to process needs.

Product discharge

For automatic product discharge, pneumatic

conveying or gravity-based systems are available for

use with the Non-Sifting Gill Plate™ air distributor

technology.

Inlet air preparation unit

Inlet air is treated using a series of filters and

conditioning units according to the sensitivity of the

process and the ambient climatic conditions. Options

range from the basic minimum, consisting of a pre-

filter, heater and final filter, to full air-conditioning to

provide consistent processing conditions all year

round. Condensers are used for dehumidifying in

most applications, but for hygroscopic or

effervescent products which require a very low dew

point, additional adsorption devices can be installed.

Humidification is achieved by an injection of steam.

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Optimized Designs

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Process filters

In granulation, drying, and most pelletizing

applications, a process filter is used to trap

mall particles, which are returned to the bed

when the filter is cleaned. In coating

applications, fine particles usually need to be

removed. Fluid beds that are used for more

than one type of process can be supplied

with interchangeable process filters.

1 Single shaker bag filter

A simple, basic filter with a single bag,

which is cleaned by shaking. Fluidization

stops during filter cleaning.

2 Multi shaker bag filter

This filter is divided into two or more

sections, with a separate filter bag in each

one. Bags are cleaned individually by

shaking the filter, while fluidization

continues in the other sections, for faster

and more efficient production.

3 Blow-back filter

There are multiple filter bag sections in this

design. Cleaning takes place one bag at a

time, so that a large proportion of the filter

is always available for continuous

fluidization.

4 Cartridge filter

Stainless steel filter cartridges are cleaned

one at a time, so that a large proportion of

the filter is always available for continuous

fluidization. Unlike bag filters, this system

can be cleaned-in-place.

5 Particle retainer

Used for coating applications, this design

retains the coarser particles and returns

them to the process, removing the dust to an

external filter unit.

Filter Heater (faceand by-pass)

Cooler/condenser

Humidifier

Pre-heater

Pre-filter

Suction fanPolice filters

Silencer

Quick closingvalve

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3

4

5

Your Process

Understanding& Controlling

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For optimum compatibility with existing plant control strategies,fluid bed systems are available with a choice of manual or FDAcompliant automated controls. Programmable logic controller(PLC) and PC-based options offer a wide range of recipe handling,data acquisition and network communication functions.

Controls

The PLC front panel key-pad and built-in monitor

are used for recipe programming and real-time

process MIMIC display.

For optimum compatibility with existing plant

control strategies, fluid bed systems are available

with a choice of manual or FDA compliant

automated controls. Programmable logic controller

(PLC) and PC-based options offer a wide range of

recipe handling, data acquisition and network

communication functions.

SynTQ PAT data analysis andmodelling platform

Process engineeringmodels

Multivariateanalysis

Materialsinformation

PAT data

Process optimisation

Drying curve monitored byNDC Pharmaveiw NIR

moisture measurement system

Monitoring coating conditionsGPS real time process humidity model

(RTPD) (above) to navigate the pychometricchart (below

Monitoring of coat growthusing Zeiss Corona NIR

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GEA Pharma Systems integrate processengineering and PAT to provide ProcessIntelligence

The FDA’s PAT (process analytical technologies)

initiative has enabled GPS Pharma Systems to

combine its equipment design skills and process

engineering know–how in order to integrate online

(PAT) analysers into its process systems in a way

which can provide real insight into the operation of

the process and help customers achieve key product

quality target .

The goal of the PAT initiative is to ensure that

pharmaceutical products are manufactured using

processes which are understood and monitored so

that the key quality characteristics of the products

can be actively controlled.

Combining process monitoring using online

analysers, together with solid process engineering

principles and advanced process modelling

techniques will enable processes to be actively

controlled in order to compensate for minor input

variations (eg. raw materials) so that the

specifications for the final product will be closer to

the ideal target.

Using process models to identify the process

conditions that highlite products which perform

best in subsequent processes will enable the whole

production process to be targeted towards the

performance of the final dose rather than just

optimising each unit operation individually. GPS

Pharma Systems wide scope gives it a unique

perspective on the complete process.

Lighthouse Probe™Technology

GEA Pharma Systems (GPS) has joinedforces with J&M GmbH to create acompact and cleanable in-process opticalprobe for use in powder processingequipment.

The result is the novel Lighthouse Probe™, which

can be used with a range of spectroscopic

techniques, including NIR and UV/vis, to overcome

the traditional problem of product sticking to

observation windows.

The probe is compact and easy to install and makes

it possible to take a reliable in process measurement

of quality critical product characteristics including:

• Material and active content identification

• Active content uniformity during high shear

blending operations

• Moisture content and end-point during

drying processes

• Coat growth during coating processes

Optical methods such as UV/Vis or NIR

spectroscopy can be very powerful tools for

analysing a range of product characteristics, but in

processes involving wet and sticky powders it is

necessary to ensure that the system has a clear view

of the product. Conventional windows used in

process equipment such as fluid bed systems or high

shear granulators, have always suffered from the

risk of window fouling. The new GPS & J&M

Lighthouse Probe™ has overcome this problem.

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In processs measurement position Clean and calibrate position CIP position at end of process

Production capacities

150 300 400 400 600 800 1200 1800 2400 3000(Size 3) (Size 4) (Size 5) (Size 5) K3 (Size 6) (Size 6) K3 (Size 7) (Size 8) (Size 9) (Size 10)

Typical working

capacity 30 to 100 L 60 to 200 L 90 to 300 L 90 to 400 L 120 to 400 L 120 to 600 L 240 to 800 L 360 to 1200 L 480 to 1600 L 600 to 2000 L

Typical batch

capacity

(average product density 0.5kg/l) 15 to 50 kg 30 to 100 kg 45 to 150 kg 60 to 200 kg 60 to 200 kg 90 to 300 kg 120 to 400 kg 180 to 600 kg 240 - 800 kgs 320 to 1200 kg

Maximum

working volume 125 L 225 L 355 L 450 L 600 L 650 L 900 L 1350 L 1800 L 2250 L

Values are process and product specific and may vary from those shown above.

Sizes &Capacities

Meeting EveryRequirement

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Standard modules configured into tailor-made plants.

The philosophy behind the design is that a combination of

standardised modules are built together in order to meet the

requirement for a specific duty. Therefore, dryers of equal capacity

may be completely different with respect to design, configuration

and physical size.

To meet the high requirements of the pharmaceutical industry,

Aeromatic-Fielder has a series of fluid bed systems suitable for

formulation, process development, production of clinical material

through to full-scale production.

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Integration

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OptimumProcess Efficiency

System integration

GEA Pharma Systems specialises in the design and

manufacture of fluid bed and high-shear granulation

technology and is uniquely qualified to provide

state-of-the-art integrated high shear mixer-

granulator and fluid bed drying technology. Drawing

on its world-class expertise, GPS Pharma Systems

offers fully integrated turnkey installations. The

service includes: design, installation assistance,

commissioning, process validation, as well as

training, and technical support. Installation,

operation qualification and documentation are

carried out according to FDA/GAMP guidelines.

Integration by design

Aeromatic-Fielder’s entire range of process

equipment is designed with system integration in

mind. A modular approach allows customers to

select standard process modules to suit project

needs. Fluid bed dryers and coaters can be combined

with top-drive and bottom-drive high shear mixer-

granulators, wet and dry milling facilities, product

handling systems, binder and coating preparation

units, filtration units, all designed for fully

integrated systems. Safety, containment, product

flow and building requirements are in-built for full

integration for optimum process efficiency

Current Good Manufacturing Practices increasingly require thatproduct is fully contained during processing to protect operatorsand environment. Integrated process systems not only offercontainment but improved productivity through automation,increased yield and efficient cleaning procedures.

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Design

Cleanability &Maintenance

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Process optimisation depends on efficient, effectivecleaning. Automation of the cleaning process ensuresrepeatability, allows validation and minimises down-time.In recognition of the fundamental role played in today’sadvanced powder processing industry by automated clean-in-place procedures Aeromatic-Fielder has developed aunique approach to CIP.

WIP and CIP

All process plant can be supplied with a basic wash-

in-place (WIP) system or with fully automated

cleaning-in-place system. CIP options for the fluid bed

processor include process filters that do not have to be

removed for cleaning.

CIP Kitchen

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ContinuousImprovement

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Safety &the environment

Improved safety for integrated granulation

and drying suites

Extensive safety testing confirms pressure

enhancement effects and identifies safe design

limits for integrated systems GPS Pharma Systems

in conjunction with the FSA, the safety specialist

centre in Germany, have carried out an extensive test

programme involving over 100 test explosions. This

research has shown conclusively that should an

explosion occur during the transfer operation in an

integrated system where a granulator is connected

directly to a fluid bed dryer without an explosion

isolation valve, the secondary explosion pressures in

the granulator can be significantly higher than in

the fluid bed. These tests have enabled GPS Pharma

Systems to gain full EC type approval for a range of

pressure shock resistant integrated systems and 16-

bar pressure shock resistant high shear granulators.

Safety when using organic solvents

The tests were carried out with hybrid mixtures that

behave in the same way as pharmaceutical products

containing organic solvents and showed that the final

explosion pressure in the granulator is dependent on

the volumes of the two vessels and that the length

and diameter of the interconnecting duct is critical in

ensuring that the pressure remains within safe limits.

The tests showed that where the fluid bed is designed

in accordance with VDI 2263 part 5 (i.e.: for a 10-bar

explosion pressure, which the standard considers to

be adequate for all pharmaceutical powders and

organic solvent combinations), then the granulator

must be able to withstand an over pressure of at least

16 bar to provide a range of transfer duct

configurations which are both practical and safe.

Where the fluid bed is required to handle materials

with explosion pressures greater than 10 bar (e.g.:

metal powders) - and hence is designed outside of

the VDI standard - or where the configuration of the

interconnecting duct is outside the safe design

parameters, then either the granulator must be

designed to a higher pressure shock resistance or a

hygienic fast acting valve, or some other form of

protection, is essential. The test program showed

that the pressure enhancement effects are caused by

the difference in the propagation speed between the

pressure wave and the flame front. The worst cases

are when the pressure in the granulator is able to

rise significantly before the flame can reach it and

ignite the pre-compressed material. For the range of

transfer duct configurations to be used with the 16-

bar granulator design, the presence of bends and

obstructions such as mills was not seen to affect the

increase in pressure.

For plant processing powders, or mixtures that are

not flammable at the time of transfer between the

granulator and the fluid bed, then the risk of

explosion is eliminated and hence a wider range of

transfer duct designs can be used safely. This

extensive research program has significantly

advanced the state of the art in safety technology for

pharmaceutical plants and confirms GPS Pharma

Systems’ commitment to introducing new products

which are based on sound research and development

using solid process know how and understanding.

For full compliance with national, local and in-house regulations,GPS Pharma Systems offers a range of emission control optionsincluding solvent recovery systems, outlet filters and fullcontainment plants. Equipment can be supplied to meetexplosion-proof and pressure shock standards as required.

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10 bar PSRdesign (norelief ductneccessary)

Explosionsuppression

system (no reliefduct neccessary)

2 bar PSRdesign withexplosionrelief duct

…Every Step of the Way

Based on years of experience, equipment qualification will be carried out according to

an agreed plan using documents prepared by Aeromatic-Fielder.

Our engineers will contribute to a successful qualification of the equipment in close

co-operation with your validation staff.

Working with you…

Entering a partnership with Aeromatic-Fielder means entering a partnership that does

not end until you are completely satisfied. From the moment you have specified your

user requirements and until the plant has been put into service and has been

qualified, our trained staff stays with you at every step of the process, working in

close co-operation with your own staff creating the components and systems that will

result in a finished plant.

The CompletePartnership

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Client Verification

Aeromatic-Fielder /

Client Verification

User Requirements

Functional Specification

Softwaredesign

Hardwaredesign

Mechanicaldesign

Process Qualification

Operational Qualification

Installation Qualification

FAT testing

Integrated testing

Bench testing

Mechanical equipment build

Hardware manufacturing

Software Configuration

Customerresponsibilty

Aeromatic-Fielderresponsibilty

Joint tasks

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After Sales

Regular maintenance is essential to ensure

equipment operates to maximum efficiency. Fully

trained engineers can carry out on-site servicing and

calibration of equipment, either as part of a planned

maintenance programme or in response to customer

need. Replacement parts can be supplied from stock

or manufactured to order.

To avoid the expense of equipment replacement

Aeromatic-Fielder can upgrade existing systems and

plant to meet different operational parameters, to

comply with changing regulations, or to modify for

use at another location.

Project Management

The expertise of the Aeromatic-Fielder engineering

team is available to help customers find the

optimum solution for their individual processing

needs. The company assists with single phases of a

project, or takes full responsibility for design and

installation of a complete turnkey plant.

Training

Operators of Aeromatic-Fielder equipment can

undergo training to help them maximise efficiency,

either at the time of installation or periodically as

required.

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Servicefor Life •