Freeze Dryers - GEA Pharma Systems

Process Engineering
Division
Freeze Dryers
for the Pharma &
Biotech Industry
by GEA Lyophil
Reliable & Flexible

GEA Lyophil’s range of supplies
and services comprises laboratory
freeze dryers, the pilot range for
R&D purposes and small
production batches, industrial size
freeze dryers, and complete
freeze dryer systems including
among others Automatic Loadingand
Unloading Systems (ALUS ® ).
In addition the company provides
service and retrofitting of
existing freeze dryers.
The design and manufacture of
freeze dryers and freeze drying
systems is carried out in
accordance with all cGMP,
CE, GAMP4 and 21 CFR
Part 11 guidelines.
Product Know-How
Process Expertise
GEA Lyophil’s process expertise is based
on experience and innovation secured by
R&D. With over 500 units installed
worldwide and literally thousands of tests
performed in GEA Lyophil’s own test
area the company has established a solid
base of expertise related to the needs of
the pharmaceutical and biotech industry.
2

Delivering the Right Solutions
Every GEA Lyophil freeze dryer
originates from the customer’s desire to
create a product that will succeed in the
market. In GEA Lyophil, the customer
finds a partner which will assist in
meeting that goal. The company’s
expertise in freeze drying and related
processes, i.e. isolator technology,
sterilisation and clean-in-place (CIP)
covers all kinds of pharmaceuticals and
biotechnology derived products, for
example, hormones, vaccines,
antibiotics anti-infectives, bacteria, sera,
enzymes and diagnostic agents.
Plants Customized for Success
Every pharmaceutical plant and system
from GEA Lyophil is a unique and
efficient combination of proven
technology and individual solutions
reflecting the customer’s needs. Based
on standard components, the company
supplies plants for cGMP production
configured to meet the customer’s
specific requirements.
GEA Lyophil can deliver: The right size
to meet the customer’s output demands,
the right configuration for their
production and process requirements,
and the right technology to reduce
contamination risks.
A Partnership in Every Perspective
Working with GEA Lyophil means
entering a solid and professional
partnership every step of the way, from
process testing and design to start up
and take over of the new plant ready
for production. GEA Lyophil’s
comprehensive after sales program
ensures that return on investment is
optimised throughout the lifetime
of the plant.
3

Proven Technology
and Expertise
For more than half a century
GEA Lyophil has designed and
manufactured freeze dryers
for the pharmaceutical and
biotech industry.
1950 1960 1970
1951
1952
1959
1960s
1969
1975
1980
1982
First LYOVAC ®
Freeze Dryer built
by Leybold
Application
Laboratory
Patent for PRM
(Pressure Rise
Measurement)
Pilot and
Production Scale
Freeze Dryers
Cryomicroscope
Eutectic Monitor
for Resistance
Measurements
Mushroom Valve
as Chamber/
Condenser Valve
Lyo Process
Control
4

During this time the company has
remained dedicated to the development
of freeze dryer technology and has
contributed substantially both to design
and process control as shown in the
illustration below.
GEA Lyophil was one of the first freeze
drying companies to deliver Automatic
Loading and Unloading Systems
(ALUS ® ) for freeze dryers and integrate
isolators and CIP-Skids into a complete
system with freeze dryer and ALUS.
1980 1990 2000
1985
Patent for Liquid
Nitrogen
Condenser
1988
Dome Device
and BTM
1989
1997
ALUS ® ISO 9001
Certification
1997
Delivery of first
ALUS with Isolator
technology to
Pharmaceutical
Industry
1998
1999
TLC ® Merger with
STERIS
2005
GEA Lyophil
GmbH
5

Applications of
Freeze Drying
for the Pharmaceutical & Biotech Industry
In the aseptic pharmaceutical
production as well as in the
biotech area, Freeze Drying, or
Lyophilization has a key role as
the main fill and finish process,
handling liquid products and
formulations in solutions.
Why Freeze Dry
Freeze dried products retain their
original properties. By adding water or
other solvents they can be reconstituted
easily and very quickly to a usable
solution. There is no need for cooling
during storage, therefore storage costs
decrease and handling is made easier.
6

There is a wide range of substances
for which freeze drying is used as
conservation method:
Antibiotics, Bacteria, Vaccines,
Hormones, Vitamins, Enzymes,
Ferments, Peptides, Liposomes,
Collagen, Plant extracts, Liver extracts,
Radio-immuno-essays, Blood plasma,
Plasma fractions, Antibodies.
Pilot Freeze Dryer FCM 2
Commonly, water is used as solvent,
but in some cases pharmaceutical
products need solvents based on
alcohol. In this case the freeze drying
process and subsequently the design
of the equipment will comply with
ATEX guidelines.
GEA Lyophil is able to support its
customers in the installation and
operation of a reliable, validated
lyophilization process for
pharmaceuticals and biologicals.
7

The Freeze Dryer
Product Line
GEA Lyophil’s freeze dryer
product line comprises laboratory
freeze dryers, pilot plants for R&D
purposes or small production
batches, industrial size production
freeze dryers as well as complete
freeze dryer systems consisting of
one or multiple freeze dryers plus
ALUS ® (Automatic Loading and
Unloading System) and isolators.
View into chamber of a GT 300-D
Production Plants
Large scale production plants built
to customer specifications
• Shelf Size 8 - 58 m 2
GEA Lyophil production Freeze Dryers
are either non sterilisable units or steam
respectively VHP sterilisable units for e.g.
• bulk drying for intermediate products
• blood plasma and proteins
• diagnostic agents
• sensitive components
FCM 80-D and FCM 500-D with Transfer Cart
Production Systems
Automation and highest
contamination prevention
The handling of pharmaceutical substances
such as cytostatics creates a high need for
operator and product protection.
A typical Freeze Dryer Production System
incorporates the following components:
• Multiple Freeze Dryers
• Automatic Loading and Unloading
System (ALUS ® )
• Common CIP-Skid
• Isolator or RABs
FCM 10
• SCADA System
Pilot Plants
For R & D and
Small Scale Production
• Shelf Size 0.4 - 8 m 2
GEA Lyophil offers Pilot Plants for the
following applications:
• Product development and process
cycle optimisation
• Up Scaling of the process for later use
in Production Plants
• Small scale production especially by
Biotech customers
GT 2
Lab Units
For Laboratories, Universities
and Research Institutes
• Shelf Size 0.1 - 0.3 m 2
The smallest Freeze Dryer unit in the
product line serves the following
purposes:
• First product development steps
• Preparation of substances for analysis,
e.g. biomasses
• Teaching and demonstrating of the
freeze drying process
8

Plant
Components
Features of the freeze dryers include:
Proven modules built together
offer the possibility of choosing
either a cost-effective or a highly
customised system. Each module
and system component must
meet the strictest requirements
and regulatory standards
around the world.
• Choice of configurations, e.g.
monoblock, 2-floor configurations
• Various door configurations,
including re-cooling, slot doors
and many more
• Reciprocating and screw compressors
systems as well as LN2 cooling
systems
• Automatic CIP (Clean-in-Place) and
SIP (Sterilisation-in Place) systems
offer product protection, prevent
contamination and increase the
productivity by allowing a reduction
in the number of staff needed to
operate the equipment
• Automatic WIT (Water Intrusion Test)
of the venting filters ensures integrity
and increases the availability of
the unit
• Monitored stainless steel stoppering
bellow
• Proven vacuum pump system
technology
• VHP Technology: a cost saving and
environmentally friendly alternative
to steam sterilisation
• SCADA system for controlling and
monitoring of reproducible and
documented processes, meeting
21 CFR Part 11 regulation
Sterilisation Methods
Cold Sterilisation as an Alternative to Steam Sterilisation
VHP Sterilisation for Freeze Dryers
Usually freeze dryers are sterilised by
using steam. GEA Lyophil is the only
manufacturer to offer an alternative:
sterilisation by vaporized hydrogen
peroxide. The VAPOVAC Steriliser,
which is connected to the freeze dryer,
generates vapour of hydrogen peroxide,
which is lead into the chamber and
condenser of the freeze dryer.
The sterilisation process takes
approximately 3 h depending on the
performance of the vacuum pumps;
a much shorter cycle time compared
to steam sterilisation.
The VAPOVAC Steriliser offers the
following advantages:
Cost saving:
• Lower investment costs and lower
operational costs
• Short process time
• Longer service intervals
Reliable and safe process
• Kills a variety of germs
• Achieves equal distribution of
steriliant
• No toxic residues
• Easy and safe handling
Retrofitting an existing freeze dryer
with a VAPOVAC Steriliser is a good
means of lengthening its life cycle. A
few changes to hardware, and some
software adaptation would be necessary
- a minimal effort in time and cost
compared to equipping a nonsterilisable
unit with steam sterilisation.
After the retrofit the freeze dryer will
meet current FDA standards and can
provide several more years of service.
9

Freeze Drying
Tailored Plant Configurations
The choice of freeze dryer is
driven by a variety of different
requirements with regard to:
• Features of the pharmaceutical product
• Manufacturing needs
• Space
Based on proven technology GEA
Lyophil designs freeze dryers
tailored to its customers’ needs.
This has resulted in a wide range of
different plant configurations some
examples of which are shown
on these pages.
2-Floor Installation
10

FCM design with condenser at the
rear side of the chamber
Full Size Door
Door-in-Door Design for Loading/Unloading
and Maintenance at the same side
Slot Door (Pizza Door) for ALUS
Features of the
pharmaceutical product
For many customers it is vital to
minimise contamination risks, both
product as well as the operators have to
be protected. In this case a production
system including Freeze Dryer, ALUS
and isolators is the right choice.
Manufacturing needs:
Integration into a pharmaceutical
production line may determine whether
the freeze dryer will be loaded and
unloaded at the same side, or loaded
at one side and unloaded at the
opposite side.
Space:
GEA Lyophil offers different plant
configurations such as single or twofloor
installation when choosing the GT
concept. The compact modular FCM
construction with its small footprint is
ideal for limited space on a single level.
FCM design with condenser at
the right side of the chamber
Full Size Door
Door-in-Door Design
Slot Door (Pizza Door) for ALUS
11

Minimising contamination risks
Increase Efficiency
ALUS ® (Automatic Loading and Unloading Systems)
Human intervention in the loading of
the freeze dryer means the highest risk
of contamination. The use of ALUS
minimises this risk as the number of
operators in this area can be reduced,
therefore less operator monitoring for
contamination is necessary. At the same
time the automated loading and
unloading process is much shorter
compared to manual loading.
Freeze Dryer with ALUS
(Conveyor-Pusher-System)
GEA Lyophil has designed and
manufactured ALUS since 1989, and
was one of the first manufacturers to
develop this technology using
permanently installed systems, as well
as automatic guided vehicles (AGV).
12

Enabling PAT
Thermodynamic Lyophilization Control TLC ®
During the freeze drying process, the ice
temperature is the key parameter to
monitor and control!
A safe, reliable, reproducible process is
Efficient, safe and
reliable performance
with the following
key features:
• High throughput with loading speed
of up to 400 vials per minute and
unloading speed of up to 700 vials per
minute
• High flexibility for different vial
formats
• High safety of operation and stability
for all vial formats, even small ones
with a diameter/height ratio of

From
Specification…
Freeze Drying
Expertise
On hand throughout the whole
life cycle of the plant.
From pre-engineering studies, to the
specification of the plant and SAT, (Site
Acceptance Test) to qualification and
validation support, GEA Lyophil’s
experts remain on hand to ensure that
the equipment operates efficiently and
reliably within the shortest possible
time frame.
Professional training of customers’
operators, preventive maintenance
together with excellent parts availability
and application support guarantees the
trouble fee and profitable operation of
GEA Lyophil freeze dryers. GEA
Lyophil’s retrofit expertise enables
customers to extend the life of their
freeze dryers and to cope with changing
requirements and regulations.
14

… to
Retrofit
Services
Services includes:
• Preventive maintenance contracts
• Spare parts
• 24 h/s 7d/week Hotline
• Operator Training
• Calibration Services
• Qualification Services
• Validation Services
Retrofits
Retrofits include:
• Optimisation and upgrading of process
control systems including IQ/OQ’s, e.g.
- In compliance with 21 CFR Part 11
- Adaption from Siemens S5 to
Siemens S7
• Integration of new process features
in existing references and revamping
of mechanical components and/or
existing freeze drying plants
-Integrity test
-VHP sterilisation
-New shelf package
-ALUS
-Refrigeration system or components
Application Support
Assistance in product cycle
optimisation via:
• Cryomicroscopical examinations
• Electrical resistance and temperature
measurements
• Residual moisture measurements
(Karl Fischer Method)
• Determination of the eutectic point
• Thermodynamic Lyophilization
Control (TLC ® )
• Freeze drying test campaigns in own
pilot freeze dryers
Customer
responsibilty
Planning
Validation Report
User Requirements
Performance Qualification
Joint tasks
Functional Specification
Operational Qualification
Scada Design
(MW & SW)
PLC Design
(MW & SW)
Electrical &
Mechanical Design
Installation Qualification
GxP & Safety Review
Module & Integration Tests
GEA Lyophil
responsibility
Electrical & Mechanical
Construction Practice
Build PLC. Good Programming
Practice & Source Code Review
Build Scada. Good Programming
& Practice & Source Code Review
15

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, Niro Pharma Systems offers
manufacturers all over the world the
opportunity to enter into a profitable partnership for
development and contract. NPS combine advanced inhouse
technology with a thorough understanding of the
pharmaceutical industry to help customers maximize
their development results.
Niro 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, Niro 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.
Sales enquiries:
GEA Lyophil GmbH
Kalscheurener Strasse 92
D-50354 Hürth · Germany
Tel: +49 2233 6999-0 · Fax: +49 2233 6999-10
E-mail: info@gea-lyophil.com
For North America Contact:
Niro Pharma Systems
9165 Rumsey Road
Columbia · Maryland 21045, USA
Tel: +1 410 997 7010 · Fax: +1 410 997 5021
E-mail: info@niroinc.com
NPS-GEA Lyophil © Niro Pharma Systems 2006 Specifications subject to change without notice All trademarks recognized
W W W . N I R O P H A R M A . C O M
Process Engineering
Division
GEA Lyophil GmbH
A company of GEA Group