Grâce aux vannes stériles VESTA®, La nouvelle production de vaccins réponds déjà aux exigences de demain.
Ce n'est pas sans raison si la planification et la mise en place de lignes de production pour l'industrie pharmaceutique est considérée comme la discipline reine du génie civil. Les défis sont - pour ne citer que quelques exemples - de satisfaire aux exigences d'hygiène les plus strictes, travailler dans des espaces confinés et bien entendu faciliter la maintenance lors de la conception de l'usine. Une autre condition essentielle est de faciliter la mise en oeuvre de futures évolutions, telles que les nouveaux produits ou process, sans qu'il ne soit nécessaire d'effectuer des modifications majeures. La nouvelle installation de production pour vaccins de Baxter à Vienne montre comment les propriétaires et ingénieurs des usines doivent travailler en étroite collaboration avec les fournisseurs de composants, afin de trouver eds solution intelligentes qui répondent à toutes ces exigences.
Photo 1: The so-called process trolley (shown here) and the media panel form the centrepiece of the new product formulation line, where weighing and metering of all formulation components takes place.
Photo 2: The media panel forms the central interface between all pipes in the formulation area and the pipes to the product tanks, it also accommodates all CIP and SIP connections.
Baxter, a global leading supplier of medical and pharmaceutical products, produce biotechnology-based drugs and vaccines at their Austrian locations in Orth on the Danube and Vienna. The research centre in Vienna is the company’s largest in the world. The majority of the pharmaceuticals produced in Austria is exported. To satisfy the ever-growing demand, the company built a new production facility for the production of vaccines in Vienna in 2009. zeta Biopharma GmbH, based in Tobelbad near Graz, Austria, was awarded the order for the complete formulation line. The specialist for biotechnological and pharmaceutical process technology was responsible for the overall engineering and implementation of the plant including the automation system. Special solutions for valve technology were supplied by GEA Tuchenhagen GmbH.
Flexibility in product formulation
The plant comprises functional units for product formulation, product filtration and units for supplying cooled product to the downstream syringe filling line. When designing the product formulation area, the highest priority was given to flexibility: the formulation system was not to be designed for once-defined procedures but permit new products or production sequences to be easily adopted. To meet this requirement, an entirely new formulation concept was developed. The so-called process trolley and the media panel now form the centrepiece of the new product formulation system, where weighing and metering of all formulation ingredients are carried out. The process trolley supplies all the necessary components, which are typically delivered in disposable bags. Up to 50 components can be made available at the same time, so that complex formulations can also be prepared in a single operation. The bags are connected via hoses to a central collecting pipe. Metering is controlled by the supervisory control system in accordance with the current formula; weighing stations allow accurate measuring, even of very small component volumes (photo 1).
The central collecting pipe conveys the components to a filtration block with a sterile product filter and on to the media panel. The pipes from the formulation area and the pipes to the product tanks come together at this panel, which also accommodates all CIP and SIP connections; the relevant pipe routes are enabled by swing bend panels (photo 2). Bringing all pipes together at the media panel enables various functions to be carried out simultaneously without any problems. Production can continue in one area while cleaning is running in another. Both processes are reliably separated from each other, the correct position of all swing bends is constantly monitored by the supervisory control system.
Sterile valves with bellows preferred
Photo 3: Instead of the classic, central tank-bottom valve, three tank-bottom valves of the VESTA® series were installed, two of them laterally at the cup-shaped tank wall, another centrally at the bottom.
Another special characteristic of this system is that apart from the bellows and the valve housing no other parts come in contact with the product so that potential problems with elastomers are reliably excluded. The special design of the valve housings is free from any dead space and – in contrast to the frequently used diaphragm valves – is self-draining in almost all installation positions.
To perform maintenance, just the groove nut which connects the actuator and the valve body needs to be released. The actuator can then be removed together with the bellows. The bellows can be replaced in next to no time. No tools are required.
Agitator tank for the finished product
The tanks have been designed so that the product can still be reliably cooled and agitated when the tank level is rather low. To allow for small minimum volumes, both the tank geometry and the filling/emptying concepts have been modified. All tanks have a cup-shaped cavity at the bottom. Instead of the classic, single tank-bottom valve at the central outlet, three tank-bottom valves of the VESTA® series were provided, two of them fitted laterally to the tank wall, another centrally at the bottom (photo 3). The two lateral valves are used for filling and emptying the tank and are connected to two supply lines each; the product is discharged via the bottom valve. This means that each tank has five docking points, enabling fast and flexible product handling.
All tank-bottom valves allow CIP/SIP independently from the tank. Due to the lateral installation position, natural draining of the valves is impeded. GEA Tuchenhagen has therefore modified the valves to suit this special application. The pipe connections to the valve housing were shortened and slightly inclined, so that full draining of residues can be ensured.
The finished formulations are made available for filling in cooled tanks with an integrated magnetic agitator of the zeta bio-M series. Two tank sizes are used. Each of the tanks is installed in a separate room, which permits one tank to be filled with product, while the filling line is supplied from the second tank and cleaning is running in the third. These processes are reliably separated from one another. The tanks are mobile so that they can be placed in the immediate vicinity of the filling line when the product is required for filling. With the VESTA® series designed by GEA Tuchenhagen, specialized in the manufacture of valves and components for processes where hygiene is critical for 80 years now, a new sterile valve technology is used for the first time in this plant. Baxter, as the owner of the plant, selected these valves mainly because of the straightforward valve design and the ease of maintenance they provide. The valves are based on seat valve technology with PTFE bellows, which ensures hermetic sealing of the process chamber against the outside areas and is thus suitable for sterile applications. The bellows is sealed against the valve housing by a patented sealing system: a sealing lip integrated in the bellows. The geometry of the valve parts has been designed so that they are centrally aligned automatically during assembly. A metallic stop prevents damage to the sealing lip as a result of excessive compression.
VESTA® Multiport ring distribution system instead of diaphragm valve blocks
Photo 4: The ring distribution systems of the VESTA® series are free from any dead space and are characterized by their compact design.
To distribute the flow of media to the relevant sections of the plant, ring distribution systems of the VESTA® series are used (photo 4). In these systems the incoming flow of liquid is guided through a ring channel. Up to 12 valves can be integrated on this ring to distribute the media. The use of special bellows designs in the ring valves ensures that the distribution system is free from dead space and is self-draining. The ring design of the distribution system constantly keeps the liquid in motion. Dead ends, where the medium stagnates – as they can exist in distributor blocks using diaphragm valves – are therefore avoided. Ring distributors also permit considerably more compact designs as the valves are fitted directly to the ring channel and do not need to be arranged in series as on diaphragm valve blocks. Plant layouts can therefore be configured to need less floor space.
Another special feature of VESTA® valves: they can easily be used as control valves. The bottom side of the bellows is similar in shape to a control cone so that the valve can be used for flow control without any design modification. The only difference is that the actuator needs to be replaced by a positioner, which allows flow rate control at an accuracy of +/- 1 percent.
In the Vienna plant, the valves are used for compressed air supply control. Subsequent conversion of standard shut-off valves to control valves is also possible, should future changes in the process sequence require additional control functions.
3D planning
Due to the body design of VESTA® valves, there is a slight difference in height of the inlet and outlet ports, which needed to be taken into account when planning the pipe system. Furthermore, the available space in some areas was restricted. Especially for this kind of project conditions, planning the entire plant using a 3D model offers great advantages. This way it was possible to attend to important plant details, like ensuring that all pipes can drain naturally, before starting installation work. Easy access to all components for subsequent maintenance work was also taken into account at this stage.
Summary
Flexibility, ease of maintenance and operational reliability are key criteria in a pharmaceutical production plant, but it is not easy to meet all of these criteria in practice at the same time. The example of Baxter’s new vaccine production facility in Vienna shows that the cooperation of plant owner, plant engineers and component suppliers can result in a plant which meets all those needs.
Nous tenons à remercier Beatrix Spannbauer (Project Manager chez Baxter, Vienna) et David Haidinger (Project Manager chez zeta Biopharma, Tobelbad), pour leur support lors de la rédaction de cet article.