Competence in Lyophilization Systems

Transcription

1 Competence in Lyophilization Systems

2 2 COMPETENCE IN LYOPHILIZATION SYSTEMS

3 COMPETENCE IN LYOPHILIZATION SYSTEMS 3 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 ) 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.

4 4 COMPETENCE IN LYOPHILIZATION SYSTEMS Delivering the Right Solutions GEA 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 cleanin-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.

5 COMPETENCE IN LYOPHILIZATION SYSTEMS 5 Application Support Freeze 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.

6 6 COMPETENCE IN LYOPHILIZATION SYSTEMS Freeze Dryer Product Portfolio Technology Leadership 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. LYOVAC Freeze Dryer FCM 600-D

7 COMPETENCE IN LYOPHILIZATION SYSTEMS 7 Production Freeze Dryer LYOVAC FCM 600-D LYOVAC FCM 600-D Condenser of LYOVAC Freeze Dryer

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9 COMPETENCE IN LYOPHILIZATION SYSTEMS 9 Efficient Freeze Drying for Greater Productivity Each project is different but the goal is the same: high quality and cost efficiency 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-ofthe-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. INTEGRATED FAT to verify the performance and functionality of the integrated system.

10 10 COMPETENCE IN LYOPHILIZATION SYSTEMS Process Analytical Technology (PAT) for Lyophilization: LYOPLUS The LYOPLUS mass spectrometer is a multipurpose measurement 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: standard (1 200 AMU or AMU optional) High conductance inlet system Max. operating pressure: 1 mbar Detection limit: 1ppm of non-interfering species

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12 12 COMPETENCE IN LYOPHILIZATION SYSTEMS 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.

13 COMPETENCE IN LYOPHILIZATION SYSTEMS 13 ALUS Transfer Cart Production Line with ALUS Cross moveable Transfer Cart

14 14 COMPETENCE IN LYOPHILIZATION SYSTEMS Increased Productivity and Better Contamination Control

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16 16 COMPETENCE IN LYOPHILIZATION SYSTEMS Containment/Barrier Systems 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 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.

17 COMPETENCE IN LYOPHILIZATION SYSTEMS 17 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

18 18 COMPETENCE IN LYOPHILIZATION SYSTEMS ALUS Transfer Cart System Disposable, low-cost high containment materials handling 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-ofthe-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 (diameterheight 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 Unloading Table ALUS Transfer Cart with formatting and unloading table

19 COMPETENCE IN LYOPHILIZATION SYSTEMS 19 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 productrelated 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

20 20 COMPETENCE IN LYOPHILIZATION SYSTEMS ALUS Options 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 anticounterfeiting 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. 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

21 COMPETENCE IN LYOPHILIZATION SYSTEMS 21 Backpusher The ALUS Backpusher provides the following benefits: improved user access and cleanability, costeffective 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. Vial Traceability 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 ALUS TM 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. ALUS Bellow Pusher 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. ALUS with Backpusher 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. ALUS with Starwheel

22 22 COMPETENCE IN LYOPHILIZATION SYSTEMS Lifecycle Partnership GEA will be your partner during every step of your project 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. Service, preventive maintenance, Retrofit Planning & Engineering Commissioning and Start up Project execution, Assembly and FAT

23 Our specialists are in control of all site activities. COMPETENCE IN LYOPHILIZATION SYSTEMS 23

24 We live our values. Excellence Passion Integrity Responsibility GEA-versity 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. GEA Lyophil GmbH Kalscheurener Straße 92, Tel +49 (0) Hürth, Germany pharma@gea.com gea.com GEA Group 2017 (Pharma). Specifications subject to change without notice. All trademarks recognised. All copyrights reserved. Under no circumstances should this document or any part of it be copied without written consent.