Competence in Lyophilization Systems
2 · COMPETENCE IN LYOPHILIZATION SYSTEMS
For more than 60 years, GEA has designed and
manufactured integrated freeze drying systems for
the biopharmaceutical industry: from laboratory and
pilot-scale products for R&D and small production
batches to complete, industrial-scale solutions,
including ALUS™, integrated isolators and CIP-skids.
With our extensive portfolio of loading systems,
and our expertise and know-how, we can ensure
maximum performance with high flexibility.
As a long-term partner to the pharmaceutical and
biotech industries, our equipment stands for high
performance, reliable and trouble-free operation.
And, with more than 200 validated ALUS™
installations, worldwide, we have an unparalleled
history of innovation for various pharmaceutical
applications that demonstrate our capability.
Whether filler or capper, our extensive experience in
interface design guarantees the smooth integration
of a perfectly harmonized production line. We
can help you to determine whether your specific
application requires an ALUS™ with open or closed
RABS (cRABS), isolators or the use of a stationary
push-pull system, based on your containment
requirements and product details.
Increasingly stringent health and safety
requirements for aseptic manufacturing and
contamination prevention have driven the
development of ALUS™, to which GEA has made
a major contribution. Automating the production
process and reducing the use of isolators has made
it possible to decrease human intervention in sterile
areas and minimize contamination risks.
Competence in Lyophilization Systems
GEA is one of the world’s market leaders in Freeze Drying / Lyophilization technology with a reference record of over 1000 Freeze Dryer installations worldwide, and has installed over 200 production systems that include automatic loading systems (ALUS™)
COMPETENCE IN LYOPHILIZATION SYSTEMS · 3
Delivering the Right SolutionsGEA’s process expertise is based on experience and innovation secured by R&D
Having completed thousands of tests in GEA’s own
Liquid Dosage test area, the company has established
a solid base of expertise related to the needs of
the pharmaceutical and biotech industries.
Every GEA freeze dryer is designed to help customers
to create a product that will succeed in the market,
with GEA being a partner in reaching that goal.
GEA’s range of supplies and services comprises:
pilot-scale freeze dryers for R&D purposes and small
production batches; industrialsize freeze dryers; and
complete freeze dryer systems including Automatic
Loading and Unloading Systems (ALUS™). In addition, the
company services and retrofits existing freeze dryers.
The design and manufacture of freeze dryers and
freeze drying systems is done in accordance with all
cGMP, CE, GAMP5 and 21 CFR Part 11 guidelines.
The company’s expertise in freeze drying and related
processes — isolator technology, sterilization and clean-
in-place (CIP) — covers all kinds of pharmaceuticals and
biotechnology derived products, such as hormones, vaccines,
antibiotics anti-infectives, bacteria, sera, enzymes, diagnostic
agents, monochlonal antibodies (MABs) and blood products.
4 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Application SupportFreeze drying (lyophilization) has a key role in aseptic pharmaceutical and biotech production as the main fill and finish process
Freeze dried products retain their original
properties. By adding water or other solvents, they
can be reconstituted easily and very quickly.
Freeze drying is widely used as a preservation
method. Each product requires the optimization
of specific parameters during lyophilization. This
includes the initial freezing process, which is of
great importance for the structure of the final
product. The selected shelf temperatures and the
corresponding sublimation pressure during primary
drying not only determine the drying time, but also
the quality of the final product. Typical quality aspects
are retention of original properties, appearance
of the cake, reconstitution time and shelf-life.
The freezing and melting behavior of the product
is tested in the laboratory to establish the correct
outcome from the start. The test results then form
the parameters for further pilot testing to develop
the freeze drying process, reduce time to market
and ensure reliable scale-up to full production.
GEA helps its customers in both the
pharmaceutical and biotech industries to
optimize their lyophilization processes.
COMPETENCE IN LYOPHILIZATION SYSTEMS · 5
In-depth process understanding
GEA provides standard or customized solutions based on
proven technology and a thorough understanding of the
individual requirements for applications including bulk APIs,
blood plasma, vaccines, hormone, antibiotics, anti-infectives,
bacteria, sera, enzymes and diagnostic agent production.
Plant configuration extends from specialized solutions
for highly potent products and all layout requirements,
and from two story units up to fully integrated systems
with multiple freeze dryers and loading systems.
• More than 60 years experience in lyophilization process
development, engineering and manufacturing
• More than 1000 freeze dryers and automated loading/
unloading systems in production globally
• References in compliance with cGMP, CE,
GAMP and 21 CFR Part 11 guidelines
• Customer base includes major pharmaceutical companies,
contract manufacturers and generics manufacturers,
demonstrating the operational reliability, quality
and productivity of GEA equipment
Our pilot-scale freeze dryers are available either
with steam or H2O2 gas sterilization and our
production units can be steam sterilized.
We care about your business
Superior performance, reliability and cost-effective
production combine to keep you ahead of the competition.
Freeze Dryer Product Portfolio
Technology Leadership
LYOVAC™ Freeze Dryer FCM 600-D
6 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Production Freeze Dryer
LYOVAC™ FCM 600-D
LYOVAC™ FCM 600-D
Condenser of LYOVAC Freeze Dryer
COMPETENCE IN LYOPHILIZATION SYSTEMS · 7
8 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Plants customized for success
Every pharmaceutical system and unit from GEA is a unique
and efficient combination of proven technology and solutions
that’s individually configured for cGMP production to reflect the
specific customer’s needs
GEA can deliver the right size and performance to meet your
output demands, the right configuration for your production
and process requirements, and the right barrier technology to
eliminate contamination risks.
A partnership in every perspective
Working with GEA means entering a professional partnership
that continues every step of the way: from first process/product
testing and plant design to start up, installation, commissioning
and professional support during years of productive operation.
GEA’s unique service program and retrofit concept ensures an
optimized return on investment throughout the lifetime of
the plant.
Total cost of ownership
Buying a freeze drying system means starting a relationship
between a customer, the equipment and a supplier for 20 or more
years. Looking at the total cost during the lifetime of a plant is
essential for our clients in today’s competitive landscape. GEA has
focused all its efforts on developing smart solutions that provide
tangible benefits in terms of the efficiency and productivity of
their freeze drying plant. Green, low-energy technology, state-of-
the-art components and unique equipment design ensure the
most economical operation of the plant. At the same time, the
outstanding quality of the equipment and specific conditional
maintenance programs ensure uniquely high plant performance
and availability, which leads to increased productivity for the user.
All our efforts serve one goal: to make our customers perform better
and more cost effectively – long term.
E-STAR™ energy saving concept
Freeze drying is an energy intense operation. Yet, with
E-STAR™, process efficiencies of up to 40% are possible.
Although the process of freezing and water sublimation can’t be
changed, E-STAR™ provides a way of reducing both media and
and electricity consumption.
It addresses the need to select highly energy efficient
components and evaluates the specific energy/media
saving technologies that are available.
Efficient Freeze Drying for Greater Productivity
Each project is different but the goal is the same: high quality and cost efficiency
INTEGRATED FATto verify the performance and functionality
of the integrated system.
COMPETENCE IN LYOPHILIZATION SYSTEMS · 9
Process Analytical Technology (PAT)for Lyophilization: LYOPLUS™
The LYOPLUS™ mass spectrometer is a multipurposemeasurement device for pharmaceutical freeze drying
Originally developed to detect very small traces of silicone
oil inside freeze dryers, the LYOPLUS™ mass spectrometer
is fitted with advanced software that facilitates the collection
and measurement of data than wouldn’t be possible with
ordinary equipment. The system is able to work alongside any
existing PLC/SCADA system as a standalone unit or can be
fully integrated into the control system. It can also be operated
independently as a monitoring device that does not interfere
with any qualified processes. In addition to being able to
detect trace levels of silicone oil, thereby preventing product
contamination, LYOPLUS™ is also able to monitor the moisture
content in the freeze drying chamber during the drying cycle
— helping to define primary and secondary drying endpoints
— and reduce leak detection times down to just one hour.
LYOPLUS™ performs all these three tests in one single unit,
improving productivity, reducing power consumption and the
environmental impact of the process, and saving the user time
and money.
Silicone oil detection
Silicone oil is used to transfer heat energy to the product. After
years of operation, the harsh conditions in the dryer can lead to
small leaks and, as a consequence, end product contamination.
Eventually, as the leak increases, silicone oil is detected during
end product testing in quality control. But how many batches
have been contaminated? With LYOPLUS™, it is possible to
detect even small traces of silicone oil during the operating
cycle. No additional product is at put risk as the leak is detected
immediately.
Moisture content
At the start of the drying process, the chamber fills with product
derived water vapour. During the later stages, however, the
moisture level decreases significantly. LYOPLUS™ measures this
drop and correlates the data with the average product moisture
levels in the vials. This information can be used to refine drying
recipes, avoid any unnecessary drying time and predict product
drying curves based on the chamber’s moisture content.
Chamber leak tests
To prevent leak-based contamination, it is mandatory to perform
a leak test after each critical process. Using LYOPLUS™, it is
possible to reduce the time for this standard procedure down
from four hours to approximately one hour, owing to its very
high sensitivity. And, as LYOPLUS™ is permanently connected
to the system, helium leak tests can begin instantly, improving
detection times and productivity.
In short, LYOPLUS™ detects impurities before quality problems
arise, saving both time and money, and plays a key role in
maintaining high standards of safety, quality and productivity.
Technical Data
• Fully automated
• Fail-safe operation to ensure sterility and protect the
lyophilization equipment and the measurement device
• Standalone or optional full SCADA implementation
• High performance quadrupole mass spectrometer system
• Mass range: 1-100 standard
• (1–200 AMU or 1–300 AMU optional)
• High conductance inlet system
• Max. operating pressure: 1 mbar
• Detection limit: 1ppm of non-interfering species
10 · COMPETENCE IN LYOPHILIZATION SYSTEMS
COMPETENCE IN LYOPHILIZATION SYSTEMS · 11
A History of Innovation
Since the 1980s, GEA has designed, manufactured and improved the ALUS™ system and was one of the first manufacturers to develop this technology using permanently installed systems (conveyor-pusher systems), as well as flexible transfer cart systems
In 1997, the first isolator-contained ALUS™ went
into operation. Since then, several patents have been
filed that cover smooth docking flaps to reach the
freeze dryer shelves, for example, and the swivel
table. Consequently, in 2009, the decision was made
to bring design, engineering and production in
house to further develop the system and improve
integration.
Available as a manually operated, semiautomated
and fully automated system, depending on user
requirements, ALUS™ offers yet another advantage:
unproductive loading times can be significantly
reduced.
The use of a transfer cart, when combined with
several freeze dryers, is particularly effective, as
formatting and loading can be run in parallel. A high
throughput rate of 500 vials/min. (loading) and a
maximum speed of 800 vials/min. (unloading) can
be achieved, with both ALUS™ systems. Tool-free
size changes can be done quickly and easily, simply
by exchanging prefabricated parts. A fully automatic
size change for 2–50 mL vials is also possible. As
such, the overall turnaround time is greatly reduced,
which also benefits the customer in terms of total
cost of ownership.
ALUS™ Automatic Loading and Unloading Systems
minimize the risk of operator/product contamination
while loading and unloading a freeze dryer. Offering
shorter cycle times, improved productivity and, using
state-of-the-art monitoring systems, they also reduce
operational costs.
12 · COMPETENCE IN LYOPHILIZATION SYSTEMS
ALUS™ Transfer Cart
Production Line with ALUS™ Cross moveable Transfer Cart
COMPETENCE IN LYOPHILIZATION SYSTEMS · 13
Increased Productivity and Better Contamination Control
14 · COMPETENCE IN LYOPHILIZATION SYSTEMS
COMPETENCE IN LYOPHILIZATION SYSTEMS · 15
Containment/Barrier Systems
Restricted Access Barriers Systems (RABS) are another way to
reduce the interventions that can occur in cleanroom processing
through the use of a barrier and dynamic air flow, and can be a
viable alternative to isolators.
Both are devices that provide a physical and aerodynamic
(air overpressure) barrier between the external cleanroom
environment and a work process. The isolator design is the
more dependable of the two barrier design choices as it prevents
contamination hazards by achieving a more comprehensive
separation of the processing environment from the surrounding
facility. Nonetheless, both isolator and RABS designs are
contemporary approaches that have continued to develop during
the last 35 years and offer significant advantages compared
with previous solutions that were far more prone to microbial
contamination problems.
Aseptic processing evolved in the 1980s and 1990s with the use of isolators to separate the operator from the “critical zone” and thus reduce product risk
16 · COMPETENCE IN LYOPHILIZATION16 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Barrier and isolator systems are widely used in a number
of industries; in pharmaceutical processing — from sterile
injectable drug filling to cytotoxic sterile drug compounding —
they are primarily employed to maintain the sterility of a drug
product. Furthermore, automatic loading and unloading systems
such as GEA’s ALUS™ minimize the risk of contamination by
human intervention during the loading/unloading of freeze
dryers. Product handling rates are much higher when using
an automated process as the time spent loading/unloading the
freeze dryer is much shorter compared with manual loading.
And, as these state-of-the-art systems significantly reduce
the number of workers needed to operate the machinery,
manufacturing costs are also much lower. Plus, as some
procedures can be done unattended, SAL levels are
concomitantly higher. Perhaps more importantly, greater levels
of operator protection can be achieved, particularly when
handling potent compounds.
Caption caption caption caption
COMPETENCE IN LYOPHILIZATION SYSTEMS · 17
The ALUS™ transfer cart system takes the whole process further
by offering a flexible layout, more compact design, an advanced
control system, easy docking under laminar flow, open RABS
and the ability to expand the system by adding additional
freeze dryers when production demands increase. Formatting
and loading can run in parallel, thus optimizing the process.
The mobile Transfer Cart System distinguishes itself owing
to its high flexibility when charging several freeze dryers. The
application of the unique gapless docking technique – no gap
between the freeze dryer and transfer cart – means that we can
guarantee maximum product protection and ensure that the
transfer of the vials occurs under a constant laminar flow.
Both designs are extremely adaptable with regard to primary
packing and the degree of automation. Modifications
can be made, according to demand, within a range from
manual to fully automatic handling. Both systems can
be executed in accordance with the ATEX guidelines,
are modular, and can be retrofitted to existing units.
The new transfer cart ALUS™ is controlled using a state-of-
the-art wireless W-LAN panel. This provides precise control
of the system without requiring a hard-wired connection. The
wireless panel is much easier to handle when operating in a
cleanroom and is easier to clean than hardwired equipment.
Up to ten freeze dryers can be loaded and unloaded with
a single ALUS™ transfer cart system (depending on the
application) so, as a system grows, additional production can
easily be accommodated. This is a more flexible system than
fixed push-pull equipment and much more cost-effective.
The GEA ALUS™ stands for safety,
performance, flexibility and reliability
• High performance by charging of up to 800 vials/min and
discharging of up to 700 vials/min
• Frameless operation
• High flexibility when operating with different vial forms
• Proven operational safety, even for difficult vials (diameter-
height ratio of <3) owing to our unique patented design
• Superior sterile design with excellent laminar flow properties:
no moving parts above open vials so as to increase safety and
avoid product contamination
• Optimum interface co-ordination with upstream and
downstream equipment
• Zone-type construction for containment according to product
flow requirements
ALUS™ Transfer Cart SystemDisposable, low-cost high containment materials handling
ALUS™ Transfer Cart Unloading Table ALUS™ Transfer Cart with formatting and unloading table
18 · COMPETENCE IN LYOPHILIZATION SYSTEMS
ALUS™ from GEA represents safety, performance,
flexibility and reliability. Key features include
loading speeds of up to 500 vials per minute and
unloading speeds of up to 700 vials per minute,
high operational safety, even for difficult vials with a
diameter:height ratio of <3, high levels of flexibility
for different vial formats, excellent integration of
ALUS™ and the freeze dryer through optimum
interface coordination and integration, patented
design allows smooth transition of vials from ALUS™
to the freeze dryer, design complies with zone
concept: no machine drives in vial processing area,
frameless operation, high quality sterile design with
excellent laminar flow properties, no moving parts
above open vials increases safety and avoids product
contamination, and easy-to-use integrated software.
In 1989, the ALUS™ system instigated a paradigm
shift in lyophilization technology: back then, the
freeze dryer was the main element in a sterile
production supply chain; now ALUS™ is the key
component: a vital part of contamination risk
minimization during safe and sterile production.
Stationary push-pull system
The decision to use ALUS™ will be based on
specific containment requirements and product-
related details. If it is necessary to use ALUS™
in conjunction with closed RABS (cRABS) or
isolators, then a fixed conveyer-pusher system
should be deployed. It is not only designed
for use with cRABS, but also in an isolator.
Stationary Push-Pull System ALUS™ Buffer conveyor
COMPETENCE IN LYOPHILIZATION SYSTEMS · 19
ALUS™ Options
• unique marking of your
primary packaging
• clear characterization in
accordance with the new EU
counterfeiting directive
• 100% traceability
• a continuous quality inspection
• 100% line clearance (packaging
reporting procedure)
• precise sampling
• extensive process monitoring
To further enhance the productivity of GEA’s Automatic Loading
and Unloading Systems (ALUS™), a range of cost-effective
modular options is available to customize your freeze drying
system. Each module and system component meets strict
safety and regulatory requirements, and has been designed to
guarantee optimal product quality and high throughput rates.
100% Vial Traceability – LYODATA™
In collaboration with SCHOTT and HEUFT, GEA has developed
LYODATA™ a vial traceability solution that will help the
pharmaceutical industry to implement the EU’s drug anti-
counterfeiting directive, safeguard the rights of trademark
and patent holders and, ultimately, protect patients. We collect
data from fill to finish — at every step of the process — which
enables us, amongst others, to ensure distinctive marking for
complete traceability.
20 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Backpusher
The ALUS™ Backpusher provides the following
benefits: improved user access and cleanability, cost-
effective containment (only the product zone needs to
be LAF protected) and enhanced leak test compatibility.
Furthermore, all moving parts are bellows protected and
completely contained within the freeze dryer chamber,
facilitating CIP/SIP procedures. In addition, the system
is fully Annex 1 compliant, with no parts present above
the vials during unloading, and suitable for flat front and
isolator containment operations.
Bellow pusher
Providing a clear and defined barrier between the
product and user areas, the ALUS™ Bellow pusher
offers improved cleanability, better user access and a
cost-effective containment option (only the product zone
needs to be LAF protected). All moving parts are bellow
protected and, like the Backpusher, flat front and isolator
containment is possible.
Starwheel
During freeze dryer loading, the ALUSTM starwheel
module serves to position, count and stop — if necessary
— the vials received from the infeed conveyor to a pusher
conveyor. With processing speeds of up to 500 vials/min,
the starwheel is both time- and cost-efficient and comes in
an easy to modify format for rapid product changeovers.
Cold shelf loading
The ALUS™ cold shelf loading module from GEA offers
an efficient way to load vials onto precooled freeze dryer
shelves. Prepared vials are transported by the intermediate
pusher to the final shelf position at a rate of up 400 vials/
min. No additional change parts are required, there’s no
extra cost involved and no added buffer time for shelf
changing. In addition, the number of moving package
rows is freely selectable using the existing HMI software.
Single row unloading
Fully compatible with all types of containment (oRABS,
cRABS, isolator), the ALUS™ single row unloading
module from GEA offers an efficient way of unloading
single rows of vials at speeds of up to 400 vials/min.
The patented design provides easy vial sample handling
(track and trace) and optional vial traceability.
Vial Traceability
ALUS™ with Backpusher
ALUS™ Bellow Pusher
ALUS™ with Starwheel
COMPETENCE IN LYOPHILIZATION SYSTEMS · 21
GEA will be your partner during every step of your project
including: cycle development, analysis of your initial project
requirement, selection of the best suitable layout and right
size and system performance, equipment engineering and
manufacture, commissioning of the plant, training and lifetime
support by our service team and process experts. GEA will
be your partner during every step of your project including:
cycle development, analysis of your initial project requirement,
selection of the best suitable layout and right size and system
performance, equipment engineering and manufacture,
commissioning of the plant, training and lifetime support by our
service team and process experts. Everything from one source
and based on 60 years of freeze drying expertise.
GEA Freeze Drying Systems include the actual freeze dryer and
the automatic loading and unloading system ALUS™ integrated
in one package. From concept through design, assembly and
FAT, it’s a seamless approach without an external interface.
The benefit of this integrated concept has been tested during
FAT testing of actual performance with vials. This ensures
the smooth operation of the complete plant and proof of
performance before the equipment is shipped to site. Our
customers can be assured of a consistent security of outcome;
we take responsibility.
• Our Service Team offers 24/7 HOTLINE support.
• Intelligence built into the system, with our conditional
maintenance program, ensures the operational
availability of the plant and the highest productivity.
• Working with GEA means entering into a partnership
with dedicated experts who all have one goal: to
support you to be the best in your business.
• Planning and engineering are carried out completely in
3D CAD.
• Mock-up is carried out together with our customers to
facilitate optimum ergonomics during operation.
• Our specialists are in control of all site activities including
SAT and training of the operators to ensure that the
plant can be put into operation reliably and quickly.
• We will assemble the complete system for FAT and
demonstrate its lifetime performance. This facilitates
quick and smooth commissioning on-site.
• Our specialists are in control of all site activities including
SAT and training of the operators to ensure that the
plant can be put into operation reliably and quickly.
Lifecycle PartnershipGEA will be your partner during every step of your project
Service,preventive
maintenance,Retro�t
Planning &Engineering
Commissioningand Start up
Projectexecution,Assembly
and FAT
22 · COMPETENCE IN LYOPHILIZATION SYSTEMS
Our specialists are in control of all site activities.
COMPETENCE IN LYOPHILIZATION SYSTEMS · 23
GEA Group is a global engineering company with multi-billion euro sales and operations in more than
50 countries. Founded in 1881, the company is one of the largest providers of innovative equipment and
process technology. GEA Group is listed in the STOXX® Europe 600 Index.
We live our values.Excellence • Passion • Integrity • Responsibility • GEA-versity
GEA Lyophil GmbH
Kalscheurener Straße 92,
50354 Hürth, Germany
Tel +49 (0) 2233 6999 0
[email protected] gea.com © G
EA G
roup
201
7 (P
harm
a). S
peci
ficat
ions
sub
ject
to
chan
ge w
ithou
t no
tice.
All
trad
emar
ks r
ecog
nise
d.A
ll co
pyrig
hts
rese
rved
. Und
er n
o ci
rcum
stan
ces
shou
ld t
his
docu
men
t or
any
par
t of
it b
e co
pied
with
out
writ
ten
cons
ent.