Dry, filtered and contained
Torsten Belger, general sales manager, Powder Systems, looks at ways of overcoming containment issues for filter dryers.
Torsten Belger, general sales manager, Powder Systems, looks at ways of overcoming containment issues for filter dryers.
There are many problems associated with solids handling in pharmaceutical filter dryers and several possible solutions. The problem-solving approach and solutions presented here can be used as an example of how pharmaceutical solids containment philosophy can be applied to other equipment, such as fluid bed dryers, centrifuges or mills.It is important to assess all aspects of the process and to understand fully material flow and operator access requirements when selecting containment equipment for a highly active pharmaceutical ingredient (HAPI) processing plant, otherwise inappropriate equipment will be selected and the end-user will not achieve the desired containment results.
In recent years, new drug developments have a recognised trend of increased potency, which has resulted in the need to implement changes in plant design and operating procedures. Some 10 years ago new plant design required 100µg/m3 operator exposure level. Five years ago levels were reduced to 10µg/m3, and today 1µg/m3 operator exposure levels are usual, with some facilities using hormones having levels of below 30ng/m3.
Filter dryers are typically used to provide a closed environment for separating and drying pharmaceutical compounds. Previously, the filtration and drying steps would have been carried out in separate process equipment, which requires additional solids handling steps when transferring solids from the separation to the drying units and comes with all the associated containment and cleaning issues.
A filter dryer is normally charged with slurry from a reactor or crystalliser vessel. The slurry is first filtered using the Nutsche filtration principle of adding pressure to the top of the slurry and a pulling vacuum at the bottom, driving liquids through a filter mesh in the bottom of the filter dryer. Depending on the chemical process and the filtration characteristics of the compound, the filter cake may be washed and re-filtered and subjected to one or more additional steps prior to being dried. Drying is achieved through thermal heat input through the jacket, base and agitator of the filter dryer. During any of these process steps, samples may be taken from the cake to check for dryness, moisture and solvent content. At the end of all of those steps the final powder is discharged from the filter dryer into a receptacle for further processing (such as milling or micronising).
cake discharge
The most important area of solids containment on a filter dryer is the cake discharge, as most of the solids in the filter dryer are being moved at this time. A number of solutions are available where a separate container filling system is connected to the filter dryer without direct integration with the filter dryer process. The agitator in the unit would be used to discharge the cake automatically without human intervention (see figure 2).
There are a number of ways to facilitate container filling using the automatic filter dryer discharge; these can include systems that incorporate continuous liner technology, rapid transfer ports (RTP), inflatable seal heads or split butterfly valve (SBV) technology (figure 3). It is possible to achieve high levels of containment and product protection with these systems. However, they address only the issue of contained container filling. Sample-taking, changing the filter media, heel removal, cleaning and inspection of the discharge housing and any potential problems with solids flow still need to be considered.
The solids discharge containment system can be integrated with the filter dryer by removing the side discharge valve housing and replacing it with a fully-sealed, closed glovebox system (see figure 4). The majority of problem areas can be overcome using this integrated solution.
The discharge hatch of the filter dryer, normally opened and closed using a pneumatic or hydraulic ram assembly, is re-engineered to be manually opened or closed within the discharge glovebox arrangement. Direct access to the internals of the filter dryer can now take place from within the fully closed and sealed containment glovebox system, without exposing either the operator or the product (figure 5). This system can be seen as simply a direct replacement of the discharge valve housing in terms of its functional abilities.
contained sampling
The same glovebox can also be used for contained sampling, with samples being removed directly from the filter dryer via a sample plug integrated into the manual discharge door. These samples are packaged within the glovebox and removed via a suitable transfer system (RTP or continuous liner). More complex sampling systems can also be integrated into the design of the glovebox, but may compromise its ergonomics, cGMP and ease of cleaning.
In some instances, especially with containment retrofits to existing filter dryers, it is not possible to fully integrate this type of discharge/sampling glovebox, but dedicated sampling gloveboxes can be integrated with the filter dryer (see figure 6).
As the standard solids discharge housing has been replaced by a fully-closed access glovebox, it is now possible to directly aid the discharge of materials that do not flow well. It is also possible to clean and inspect the discharge glovebox with integrated, automated and manual clean-in-place (CIP) tools.
Although the majority of the filter cake is being discharged using the automatic agitator discharge system, there will always be a small amount (up to 5% of total cake volume) left on the filter media after the automatic discharge. This material is referred to as the heel. Due to the thermal expansion of the filter dryer body, filter media and agitator during operation, the agitator-lowering system is designed to maintain a pre-set minimum gap between the agitator and the filter media. Depending on the size of the filter dryer, this gap can range from five to 10mm or more, and it is this that creates the heel.
Without contained direct access this heel can only be recovered by re-slurrying the material within the filter dryer and recovering it in a smaller unit or by lowering the filter dryer base and removing the heel openly and without protection for product or operator.
heel removal
Since the integrated discharge glovebox allows for contained direct access to the internals of the filter dryer, it is possible to remove a large proportion of the heel via the discharge glovebox with the use of special tools. Trials have shown that up to 95% of the heel can be removed in a contained fashion.
For filter dryers up to approximately 1m2 in filtration area, it is sufficient for only one access point to maximise the heel removal yield. However, for larger filter dryers it is recommended that an additional access point is created on the perimeter. For units with over 2m2 filtration area, there should be at least two contained access ports in addition to the discharge glovebox (figure 7).
Changing and cleaning of the filtration media is the most difficult aspect during the operation of a filter dryer. The filtration media may be constructed from cloth or sintered metal mesh and cover the entire base of the filter dryer. Successful contained inspection and changing of the mesh is possible only for filter dryers of up to about 0.2m2 filtration area, due to the physical size of the equipment involved and the access restrictions within a containment system.
ultimate solution
A number of high containment filter dryers (up to 0.2m2 filtration area) have been constructed and are operating successfully where the entire lower part is enclosed by a glovebox system (see figure 8). Such a system represents the 'ultimate solution' in containing a filter dryer, as all solids handling areas can now be enclosed. In addition, this solution will also contain the final dispensing and packaging of any discharged powder, removing the need for powder to be transferred to a separate dispensing station.
With the fully integrated heel removal/discharge glovebox it is possible to access the internals of a heated, agitated pressure vessel, and this creates a number of safety issues. To prevent access to the filter dryers when it is not safe to do so, the glovebox can be equipped with a mechanical gloveport guard/interlock system. Such a system would ensure that it is not possible to access the glovebox when the agitator is running or the filter dryer is not atmospheric; and that when the glove port guards are removed it is not possible to run the agitator or pressurise the vessel. Access to the glovebox may also be denied depending on the surface temperatures of the filter dryer.
safety features
The glovebox can also be equipped with a variety of other safety features, such as: safe change HEPA extract filters; inert atmosphere by use of nitrogen purge; extract system to maintain underpressure during operation; as well as automated pressure control system and alarm outputs should these conditions be breached.
The successful selection of a suitable solids containment system for any filter dryer, be it an existing or a new unit, depends on factors such as the required containment level, the size of the unit, and type and size of container to be discharged into. Many containment systems have been developed in recent years and, whatever the application, there is likely to be someone out there somewhere who has already evaluated the various concepts and solutions. It is essential to draw on these experiences and consult companies or individuals with the relevant background.