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Zeta – Freeze & ThawSystemsSophisticated solutions for the biopharmaceutical industry

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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.

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 transpor-ted safely. In order to bridge long distances, the frozen pro-ducts can be transported by land, sea or air. The FreezeCon-tainer® 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.

Zeta FreezeSystem®

Zeta FreezeContainer®

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 systemsFor the storage and thawing of the deep-frozen products and solutions, Zeta offers complete systems for the simultane-ous execution of the process steps with several FreezeCon-tainer®.

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Zeta FreezeController®

Zeta offers a high-performance, sophisticated solution for the loss-free freezing of products.

The FreezeController®, developed in cooperation with a renow-ned, worldwide active manufacturer of cooling units. The pri-mary 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 indispensablefor companies in the GMP sector, such as

Storage

Blow-out (blowing out of the heat-transfer fl uid)

SIP

Zeta FreezeContainer®

Temperaturemapping freezing process

Main components of the FreezeController®

The Zeta FreezeController® consists of the following maincomponents:

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.

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Zeta FreezeController®

Armoured hoses with leak-free special couplings are providedfor the rapid connection and disconnection of the FreezeCon-tainer®. Insulating sleeves are supplied with the FreezeCont-roller® 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 com-ponents permits problem-free integration into a higher-level control system. The controller of the FreezeController® per-mits centralised creation and management of users and re-cipes. 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.

Zeta FreezeController®

Leak-free quick coupling Cover seal

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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.

The product is deep-frozen in the FreezeContainer® with theaid 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 be-tween 50 and 300 litres which can be frozen to tempera-tures 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 materi-al 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.

Zeta FreezeContainer®

Zeta FreezeContainer®

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Zeta FreezeContainer®

Integration

The FreezeContainer® can be integrated easily into your exis-ting processes, since they have colour-coded valve connec-tions and there is no need to configure a software interface. After connection, the container can be filled, emptied, clea-ned, sanitised or sterilised.

Validation

The Zeta FreezeContainer® can be fully validated in ac-cordance 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 manufactu-red and documented in accordance with the current versi-ons 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 exe-cution 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 tha-wing time can be reduced even further by the use of an exter-nal 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).

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)

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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 FreezeCon-troller®, 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 canbe thawed in one of two ways:

by thawing individual containers with the aid of theFreezeController® or

by thawing several containers in parallel with the aidof the FreezeStation (thawing system)

Regardless of whether the containers are thawed individually or in parallel, the process is reproducible. A temperature pro-file 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!

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

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Zeta Holding GmbH

A-8501 Lieboch/Graz, Zetaplatz 1Phone +43 3136 / 90 10 - 0Fax +43 3136 / 90 10 - 9100eMail office@zeta.com

Zeta Biopharma GmbH

A-8501 Lieboch/Graz, Zetaplatz 1Phone +43 3136 / 90 10 - 0Fax +43 3136 / 90 10 - 9100eMail office@zeta.com

A-1150 Wien, Graumanngasse 7/B4-2Phone +43 1 / 908 10 00

Zeta Automation GmbH

D-85354 Freising, Münchner Straße 8Phone +49 8161 / 99 21 - 0Fax +49 8161 / 99 21 - 44eMail info.automation@zeta.com

CH-4147 Aesch, Bruggfeldweg 1Phone +41 61 / 702 11 11

Zeta Alro AG

CH-5102 Rupperswil, Suhrhardweg 6Phone +41 56 / 624 30 00Fax +41 56 / 566 52 59eMail office-schweiz@zeta.com

Zeta Biopharma s.r.o.

CZ-25082 Úvaly, Riegerova 12Phone +420 281 / 866 807Fax +420 281 / 866 813eMail office@zeta.com

Zeta OOO

RU-129626 MoscowProspekt Mira, 104, Bld. 2, Office 30Phone +7 495 / 721 39 41eMail russia@zeta.com