29
www.epmmagazine.com
Does deep-freezing guarantee optimum product quality? Only at temperatures below the glass transition temperature can it be assumed that there will be no more movements and structural changes in the structure of the proteins in solution. Consequently, a temperature of below -70°C was defined as a prerequisite for the freezing system for particularly sensitive products.
This special requirement is owed to the product itself, which as a highly active drug calls for special precautions in worker protection. Theoretical calculations on freezing rates were empirically confirmed in the test series. These results enabled BI to develop a concrete calculation model, which is the central element of a scientific publication commissioned by BI.
While freezing containers on an industrial scale of up to 500 l are already established practice for an industrial freezing process in the moderate temperature range, the large-scale solution for freezing highly sensitive and active pharmaceutical proteins in a low temperature range of <-70°C needed a new development. The first 200 l freezing container for freezing down to -85°C emerged in a cooperation project, which was yet another result from the many years of cooperation between ZETA and Boehringer Ingelheim in the field of freezing processes. In a series of tests with the proven ZETA PilotFreeze, the freeze and thaw processes were investigated and the effects on product quality in the form of aggregation, fragment formation, turbidity or particle formation were analysed. The efficiency of the process was the prime objective of designing the vessel geometry. Important parameters for this were the consideration of product throughput, achievable temperatures, the geometric conditions in the tank and the ice layer thicknesses achieved. Calculations for achievable cooling and thawing rates were carried out and later verified by means of experiments. The development of the new vessel included some major challenges for the ZETA engineering team; they had to find materials suited for the low temperature range that would allow a stable and safe freezing process and withstand long storage time. Another important criterion for the right choice of material was personal safety.
About ZETA: With a staff of more than 500 people and its headquarters in Lieboch/Austria and nine subsidiaries in Europe, the ZETA Group is one of the biggest suppliers of engineering, automation and process technology for biopharmaceutical applications. The product range includes high-tech equipment, pilot plants and turnkey industrial plants for the biotechnological production of pharmaceutical substances. ZETA is your expert in the development of customised process solutions along the entire development and production process for aseptic applications, from laboratory to industrial scale.
Together with the freezing systems, which serve the different process volumes, ZETA covers the entire development process of a freezing unit – from the product investigations to the freezing plant on an industrial scale. Professional project teams take the current stage of every project product into account. In this way, the mutual knowledge gain can be maximised through cooperation, the product quality can be maintained in the best possible way and the time to implement processes and set up plants can be accelerated in an optimum manner. Birgit Pittermann, Head of R&D at ZETA, sums it up: "From ZETA's point of view, the success in developing freezers for very low temperatures is due to the joint efforts made by both cooperation partners."
The ZETA facility in Lebring, Southern Styria, develops and builds products that support ZETA customers along the process of producing pharmaceutical agents. ZETA is specialised in the development, enhancement and improvement of mixing technologies and freeze & thaw systems. The solution experts of the ZETA R&D department develop innovative products and patent them together with their customers and in cooperation with research centres and universities.
CONTACT: Birgit Pittermann, Head of R&D ZETA birgit.pittermann@zeta.com
Daniela Eustacchio Marketing Specialist – Team Leader Daniela.eustacchio@zeta.com