The PMA System comprises of three machines, offering total flexibility in system design with capacities of 1–1800 l. It is the ultimate in versatility, with modular options for blending, high shear granulating and melt or wet pelletizing. The design maximizes product processing and contained handling. User-selected standard process modules are combined with advanced automation and cleaning-in-place (CIP) systems to create custom solutions that meet individual needs.
GEA supplies advanced solids processing plants for mixing and granulating to the pharmaceutical industry. This includes small capacity systems designed for R&D as well as industrial size plants for batch production of pharmaceutical compounds under cGMP conditions.
Using proven standard components, GEA can supply both simplicity and flexibility in plant design. User selected process options, cleaning equipment, control systems and PAT technologies combine in a system to meet process requirements exactly. This approach ensures that qualification and validation procedures are kept to a minimum.
What ever the subsequent production steps, the formulation of an active compound and other excipients needs to be mixed homogeneously. Low shear mixing relies on the planetary movement of the mixer arm to achieve homogeneity, while high shear mixing uses a high intensity mixing blade resulting in a homogeneous blend. Which technique is most suitable depends on the subsequent production step. We can assist in making the right choice.
To form granules out of powders a granulation liquid and mechanical energy is needed. The formation of pellets can be considered as granulation taken one step further, to achieve spherical granules. For high shear pelletization, a special mixing tool is available to optimize the process and maximise the output.
Wet Pelletizing: This process uses a rotary atomizer spray to achieve excellent dispersion of binder liquid through the mix, and a special high-speed rotation blade for maximum movement of the product, for more efficient pelletization. A PTFE container-lining minimizes the need for ‘top and tailing’, even with the most cohesive of products. Studies have shown that the PTFE liner, unique to GEA can increase production efficiency by as much as 40%. Alternatively, an extruder may be used, similar to those used for the manufacture of pellets. In a typical set-up all ingredients are pre-blended in a container after dispensing. Depending on the extruder design the liquid can be added in the extruder or mixed separately to the correct consistency. The material produced by the extruder is now transferred directly into a continuous fluid bed where it is dried to the desired moisture level.
Melt Pelletizing: This is an exceptionally fast method of producing pellets in a single step. The active material and binder are mixed in binder form then heated until the binder melts. A single batch is processed typically in just 15-20 minutes, and needs no further drying.
Critically, the process geometry of the PMA-Advanced™ is identical; modifications to the design have been made solely to benefit the user and owner in terms of ease-of-use, cleanability, process analysis and installation. The space saving PMA-Advanced™ has a small footprint and unit surface area, and service access is achieved through a GMP cover hinge. By uniting these new benefits with the proven PMA™ process technology, GEA is providing the logical solution for your granulation needs. The philosophy behind the design is that a combination of standardised options is configured into tailor-made plants to meet the requirement for a specific process (as such, granulators of equal capacity may be completely different with respect to design, configuration and physical size).
For full compliance with national, local and in-house regulations, GEA offers a range of emission control options including solvent recovery systems, outlet filters and full containment plants. Equipment can be supplied to meet explosion-proof and pressure shock standards as required.
Extensive safety testing confirms pressure enhancement effects and identifies safe design limits for integrated systems. GEA, in conjunction with the FSA, the safety specialist centre in Germany, have completed an extensive test programme involving more than 100 test explosions. This research has shown conclusively that should an explosion occur during the transfer operation in an integrated system in which a granulator is connected directly to a fluid bed dryer without an explosion isolation valve, the secondary explosion pressures in the granulator can be significantly higher than in the fluid bed. These tests have enabled GEA to gain full EC type approval for a range of pressure shock resistant integrated systems and 16-bar pressure shock resistant high shear granulators.
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Using proven standard components, GEA can supply both simplicity and flexibility in plant design. User-selected process options, cleaning equipment, control systems and PAT technologies combine in a system to meet process requirements exactly. This approach ensures that qualification and validation procedures are kept to a minimum.
Through-the-wall offers the best option in terms of cleanliness, maintenance and ATEX. By keeping the motors out of the process room, you are preventing risk of contamination coming from these difficult to clean items. Maintenance is carried out from the technical area, minimizing the need for the maintenance engineer to work in a GMP area. This makes the job easier and again reduces the risk of contamination. For ATEX, the design allows us to classify the technical area as safe. This avoids the need for costly flameproof motors, making the upgrade for working with solvents much easier. The frame mounting provides a standard format for the machine, allowing it to be constructed and installed using the same structure. This structure may be raised using standard modules to achieve the customer’s desired height. For some installations it is also possible to mount control panels on the structure, allowing qualification of the complete system prior to shipping, significantly reducing the installation time on site.
Material Filter & Shroud
Production filtration is achieved using an easily removable material filter that can be cleaned and re-used. For vacuum and CIP applications stainless steel may be utilized.
Product can be discharged from the high shear granulator directly into a receiving container, or via a sizing mill. This breaks down the granules to produce more even sizing for subsequent processing. The PMA-Advanced™ features a through-the-wall hinge-mounted sizing mill, directly connected to the discharge port, using inflatable seals. For maintenance, cleaning and product changeovers, the seals are deflated and the mill hinged away from the port, allowing full access. The TTW mounting ensures the motor and controls are kept away from the clean process area. In addition to the standard mill, CIP and Pressure Shock Resistant options are available, matching the containment and safety credentials of the main machine.
The cover is mounted on a concealed hinge mechanism allowing the cover to be lifted with the minimum effort, but keeping the counterweight in the technical area. This leads to a more GMP design, reducing surfaces, making cleaning easier. On equipment supplied with the Pressure Shock Resistant design option the hinge interlocking system is power assisted to provide safe and comfortable opening to the bowl cover.
Simple open / close ports may be mounted on the cover and used to dispense product into the mixing bowl. For potent powders, split-valve technology provides full containment during loading. The PMA-Advanced™ can also be delivered with a cone loading port, allowing for the removal of the powder loading ports from the cover, but giving permanent connection to a Gravity Loading Station, but also continuous access to open the cover.
Rapid loading can be achieved using vacuum technology. GEA’s innovative killed-vacuum technique makes for easy operation and maintenance, and only requires a standard-sized filter.
A range of nozzles are available to give the optimum binder liquid droplet size for an even distribution throughout the powder mass.
The binding solution required for granulation may be pumped into the mixing bowl using a mechanical or peristaltic pump to deliver the binder liquid to the spray nozzle. Special pumps are available for the dosing of high viscosity binders.
Alternatively a pressure pot offers fast, high-pressure delivery of the binder solution, for excellent dispersion of liquid via the binder nozzle spray system. These systems are chosen typically for small scale, R&D-sized granulators.
The GEA granulator control system can be supplied with standardised or bespoke SCADA interfaces, utilizing software, such as iFIX™ from GE Fanuc Automation, to provide data collection, management and recipe driven processes, fully compliant with FDA 21 CFR Part 11.
In order to ensure safe, efficient operation of the Granulator, the system is controlled through an industrial computer HMI, with all functions deriving from a PLC controller. This design allows the control interface to be completely washed down during product changeover. Furthermore the HMI may be upgraded to allow processing with flammable organic solvents, in an ATEX Zone 1/21 area. Completing the ATEX Zone 1/21 upgrade, flammable gases may be prevented from entering the controls enclosure in the base of the Laboratory PMA-Compact™ machines by purging with compressed air.
The physical safety of the operator is assured with the use of safety locks and proximity sensors to prevent access to the bowl and discharge when the equipment is operating. Binder addition and end point determination may be controlled through the HMI, manual control or fully automated, recipe control for the unit. Data acquisition can be delivered through a 21 CFR Part 11 compliant, on-board data capture device recording critical parameters throughout the process and allowing information downloads through an Ethernet connection.
A choice of automated end-point control facilities, with trending for process optimization, is offered with all of the system control options - manual as well as PLC-based. Options include fixed process time, automatic end-point control based on power consumption, and a high-accuracy torque-based system. Both the power- and torque based options can be used to optimize spray rate and wet massing time, for faster, more uniform granule growth. It is also possible to control in-line the growth of the granules with FBRM.
The FDA’s PAT (Process Analytical Technology) initiative has enabled GEA to combine its equipment design skills and process engineering know-how to integrate online (PAT) analyzers into its systems in a way that can provide real insight into the operation of the process and help customers to achieve key product quality targets. The goal of the PAT initiative is to ensure that pharmaceutical products are manufactured using processes that are understood and monitored so that the key quality characteristics of the products can be actively controlled.
Combining process monitoring with solid process engineering principles and advanced process modelling techniques will enable procedures to be actively controlled to compensate for minor input variations (raw materials), so that the specifications for the final product will be closer to ideal targets. Built into the control system, GEA has integrated its process knowledge to help operators monitor and control their processes. For several process steps, endpoints based on process parameters are available, and guidelines are given depending on the set points entered. In addition, GEA has experience with integrating innovative analytical tools for process monitoring and control.
GEA Pharma has joined forces with J&M Analytik AG to create a compact and cleanable in-process optical probe for use in powder processing equipment.
The result is the novel Lighthouse Probe™, which can be used with a range of spectroscopic techniques, including NIR and UV/vis, to overcome the traditional problem of product sticking to observation windows.The probe is compact and easy to install and makes it possible to take a reliable in process measurement of quality critical product characteristics including:
Optical methods such as UV/Vis or NIR spectroscopy can be very powerful tools for analysing a range of product characteristics, but in processes involving wet and sticky powders it is necessary to ensure that the system has a clear view of the product. Conventional windows used in process equipment such as fluid bed systems or high shear granulators, have always suffered from the risk of window fouling. The Lighthouse Probe™ has overcome this problem.
Automation of the cleaning process ensures repeatability, allows validation and minimizes down-time. In recognition of the fundamental role played in today’s advanced powder processing industry by automated clean-in-place procedures GEA has developed a unique approach to CIP.
The shaft seal symbolizes the many developments that the PMA has seen over its existence. The PMA-Advanced™ High Shear Granulator utilizes a cartridge-mounted seal system that exhibits excellent performance for efficacy, clean-down and wear-life, without the need to purge compressed air through the seal and into the process. Maintenance benefits include rapid replacement and condition monitoring.
The circular discharge chute design is based on “quick exit” and clean drop of granule with minimum “hang up” surfaces. The discharge valve has evolved to ensure the minimum of surfaces are exposed to the product, making it simple to clean, either manually or as part of a CIP recipe.
The Filter system can be mounted in the hinge mechanism with exhausted air passing through the centre of the hinge. This creates a less cluttered working space with fewer hoses being run in the process area to the machine. Furthermore pneumatic pipework for actuators and other similar services may also be run through the hinge.
All the high shear granulation systems can be supplied with a wide range of washing-in-place and fully automated cleaning-in-place options. CIP features include a combined vacuum cover seal which prevents product leaks, lifting impeller, automated spray head and filter cleaning, and internal O-ring seals.
With a long-established pedigree of expertise and implementation, GEA equipment and technologies meet the very stringent demands of production performance, plant and market flexibility (single and multi-product), operator safety and, of course, value. With worldwide experience and market-leading credentials, we have developed an outstanding reputation for quality and service to become the leader in contained materials handling.
During most of the manufacturing process, the APIs are inside machines or vessels which are more or less secure. The main risk of material escaping into the environment exists whenever a connection between those pieces of equipment needs to be made or broken, when a sample needs to be taken, and last, but not least, when the machines need to be cleaned after the end of a manufacturing campaign.
Using Buck® valve technologies, we provide dust-free, highly contained powder transfer solutions. Our systematic approach to design eliminates contamination and material leakage throughout the process line whilst maintaining flexibility for either CIP or COP, and meets the strictest GMP requirements in the industry. We offer a complete range of quality Intermediate Bulk Containers (IBCs) and a wide range of technologies and equipment that improve and enhance the efficiency and performance of oral solid dosage production plants: