Zeta – Freeze & ThawSystems

Zeta – Freeze & ThawSystems
Sophisticated solutions for the biopharmaceutical industry
www.zeta.com

Zeta FreezeSystem ® – Low-temperature storage and
transport of liquid pharmaceutical products & solutions
Zeta FreezeSystem ® is the answer to the problem of bridging distances and times for temperature-critical
products and solutions in the pharmaceutical sector.
Zeta FreezeSystem ®
Zeta FreezeContainer ®
The products are deep-frozen in a controlled manner in order
to ensure that they can be kept for long periods. Once they
have been frozen, the products can be stored and/or transported
safely. In order to bridge long distances, the frozen products
can be transported by land, sea or air. The FreezeContainer
® is dimensioned to fit into an LD3 air-freight container.
Long periods of time can be bridged by storing the Freeze-
Container ® in a cold-storage room or by connecting it to a
cooling station in order to keep it at the desired temperature
for a long period. When the product is needed, it is thawed in
a controlled manner up to a specific maximum temperature.
After this, the product can be cooled in the FreezeContainer ®
until it is actually required for further production steps.
The product range of the Zeta FreezeSystem® includes the
following components:
FreezeController ®
The cooling and heating unit for controlled freezing,
storing and thawing of products in the FreezeContainer ® ,
with a heating and cooling capacity of up to 12kW.
FreezeContainer ®
Stainless-steel container for freezing, transporting and
thawing the products. Available with volumes of 50 to 300
litres.
Storage and thawing systems
For the storage and thawing of the deep-frozen products and
solutions, Zeta offers complete systems for the simultaneous
execution of the process steps with several FreezeContainer
® .
2 Evolution of Technology

Zeta FreezeController ®
Zeta offers a high-performance, sophisticated solution for the loss-free freezing of products.
Zeta FreezeContainer ®
Temperaturemapping freezing process
The FreezeController ® , developed in cooperation with a renowned,
worldwide active manufacturer of cooling units. The primary
task of the FreezeController ® is the controlled freezing,
storing and thawing of liquid pharmaceutical products and
solutions in a FreezeContainer ® .
But it also offers further functions which are indispensable
for companies in the GMP sector, such as
Storage
Blow-out (blowing out of the heat-transfer fl uid)
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SIP
Main components of the FreezeController ®
The Zeta FreezeController ® consists of the following main
components:
Refrigerating machine (water-cooled)
Circulation pump
Storage tank for the heat-transfer fl uid
Automation system
The process steps of the FreezeController ® include the fi lling
and draining of the double jacket and of the cooling element.
This ensures that the heat-transfer fl uid is returned to the
FreezeController ® when the FreezeContainer ® is disconnected.

Zeta FreezeController ®
Zeta FreezeController ®
Leak-free quick coupling Cover seal
Armoured hoses with leak-free special couplings are provided
for the rapid connection and disconnection of the FreezeContainer
® . Insulating sleeves are supplied with the FreezeController
® to prevent the couplings from freezing.
Automation:
The automation system is based on a Siemens S7 controller
with Siemens WinCC visualisation. The use of standard components
permits problem-free integration into a higher-level
control system. The controller of the FreezeController permits
centralised creation and management of users and recipes.
Thanks to the standardised interfaces, data can easily be recorded
in a higher-level data acquisition system. In order to
ensure the security of your data, the controller complies with
CFR 21 Part 11.
4 Evolution of Technology

Zeta FreezeContainer ® – Optimum process integration
and trouble-free validation
With the Zeta FreezeContainer ® , you can transport your products safely all over the world, which means that
you can make use of the available production and fi lling capacities in many different locations.
Zeta FreezeContainer ®
Zeta FreezeContainer ®
The product is deep-frozen in the FreezeContainer ® with the
aid of the Zeta FreezeController ® .
The FreezeContainer ® can then be transported
by land in a refrigerated truck,
by sea in a refrigerated cell or
by air in an LD3 Envirotainer (with controlled temperature)
Design:
The Zeta FreezeContainer ® is designed for the safe freezing,
storage and thawing of liquid products and of solutions between
50 and 300 litres which can be frozen to temperatures
below -20°C (down to -40°C) within a short time. The
containers are designed to withstand temperatures between
-80°C and 150°C. Customer wishes with regard to the material
quality and the fi nish of the FreezeContainer ® can be taken
into account. The containers are available in accordance with
various container design standards such as DIN or ASME.
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Zeta FreezeContainer ®
Cooling coil
Test procedure:
During execution of the project, and as part of several
projects which have already been completed successfully,
various tests were carried out with the containers. These
included, for example:
performance tests of the cooling capacity
temperature mapping in the FreezeContainer ®
differential-pressure measurements in the inlet and
outlet lines for the heat-transfer fluid
measurements of the flow rate of the heat-transfer fluid
riboflavin test of the FreezeContainer ®
pressure-maintenance tests at ambient temperature
pressure-maintenance tests in the deep-frozen state
measurement of the surface roughness
delta-ferrite measurements
endoscopic examination of the welded seams
product extraction central pipe (determination of the
residual quantity)
Integration
The FreezeContainer ® can be integrated easily into your existing
processes, since they have colour-coded valve connections
and there is no need to configure a software interface.
After connection, the container can be filled, emptied, cleaned,
sanitised or sterilised.
Validation
The Zeta FreezeContainer ® can be fully validated in accordance
with the cGMP guidelines. This has already been
proved in various projects and documented with, amongst
other things, successful riboflavin tests.
The FreezeController ® and FreezeContainer ® are manufactured
and documented in accordance with the current versions
of GAMP (V model) and cGMP. With the documentation
provided by Zeta, they can be integrated without problems
into existing validation concepts. For the FreezeSystem ® , Zeta
possesses standardised protocols and procedures for the execution
of IQ, OQ, PQ, FAT and SAT.
Optimisation
During the development process, particular attention was paid
to achieving the shortest possible process time. In order to
reduce the freezing and thawing times, the FreezeContainer ®
has a cooling coil integrated into the container and the thawing
time can be reduced even further by the use of an external
circulation pump or a shaker.
CFD
As part of the engineering process, the arrangement of the
pipes inside the container was designed for an optimal heat
transfer by simulating the freezing and thawing with the aid of
„computational fluid dynamics“ (CFD).
6 Evolution of Technology

Zeta storage and thawing systems
Valve level
Batch formula drafting
Storage of the frozen products:
Once a product has been frozen with the aid of the FreezeController
® , it can be stored almost indefinitely. This can be done
in one of two ways:
by storing the container in a deep-freeze storeroom or
by connecting the container to a cooling station (coolant
then flows continuously through the FreezeContainer ® )
Thawing the frozen products:
Depending on the requirements, the frozen products can
be thawed in one of two ways:
by thawing individual containers with the aid of the
FreezeController ® or
by thawing several containers in parallel with the aid
of the FreezeStation (thawing system)
Regardless of whether the containers are thawed individually
or in parallel, the process is reproducible. A temperature profile
can be defined for the thawing process to ensure that
thawing is always executed with the same parameters.
After thawing, the containers are kept cool (for example, at
3°C) by the FreezeController ® or the FreezeStation, permitting
storage of the product at a minimal activity until it is needed
for the next production steps!
www.zeta.com 7

As a technology supplier of the biotechnological
and pharmaceutical industry, we design,
manufacture and install customised solutions
for renowned companies around the world.
Biopharmaceutical systems
Preparation and formulation systems
CIP/SIP- and media systems
Process equipment
Sterile plant installation
Automation solutions
Agitation and mixing technology
Freeze & thaw systems
Zeta Holding GmbH
A-8501 Lieboch/Graz, Zetaplatz 1
Phone +43 3136 / 90 10 - 0
Fax +43 3136 / 90 10 - 9100
eMail office@zeta.com
Zeta Biopharma GmbH
A-8501 Lieboch/Graz, Zetaplatz 1
Phone +43 3136 / 90 10 - 0
Fax +43 3136 / 90 10 - 9100
eMail office@zeta.com
A-1150 Wien, Graumanngasse 7/B4-2
Phone +43 1 / 9081 000
Zeta Automation GmbH
D-85354 Freising, Münchner Straße 8
Phone +49 8161 / 99 21 - 0
Fax +49 8161 / 99 21 - 44
eMail info.automation@zeta.com
CH-4147 Aesch, Bruggfeldweg 1
Phone +41 61 / 702 1111
Zeta Alro AG
CH-8964 Rudolfstetten, Bernstrasse 2
Phone +41 56 / 624 3000
Fax +41 56 / 624 3000
eMail office-schweiz@zeta.com
Zeta Biopharma s.r.o.
CZ-25082 Úvaly, Riegerova 12
Phone +420 281 / 866 807
Fax +420 281 / 866 813
eMail office@zeta.com
Zeta OOO
RUS-115093 Moscow
Serpuchowskaja B. Str. No. 44
Phone +7 495 / 721 3941
eMail russia@zeta.com
www.zeta.com