(Part of Carlisle Process Systems)
Regulatory compliance factors and Good Manufacturing Practices (GMP) stipulate that production of pharmaceuticals must be conducted in a safe, contamination-free environment that will not put the operator at risk. In recognising this requirement, it is apparent that one of the most critical areas in producing solid dosage-form pharmaceuticals is the weighing room, or dispensary, where the raw materials and ingredient-weighing operations take place, and hence where raw materials could be exposed to potential contamination or cross-contamination.
There is also a growing level of concern that many materials being handled may actually cause severe health risks to operators involved in direct production operations, in addition to the product quality issues that ineffective powder and environmental control can cause. So-called “potent compounds” are on the increase at an alarming rate, with certain compounds now in use being sufficiently active to cause irreversible operator sensitisation after only a single exposure. Containment technology can provide solutions to these problems.
First, it is important to dispel the belief that vertical laminar flow modules (VLFs) provide a safe method of controlling the environment during powder dispensing/weighing operations. VLFs provide a clean environment over certain work operations and, as such, are generally intended to provide a localised, “class 100” environment around critical areas, such as syringe filling. However, this device should never be confused with a true clean booth for powder- weighing. When VLFs are applied to powder-weighing, any airborne dust thus released is carried out from the base of the flexible enclosure into the surrounding work area. This fine particulate can create severe cross-contamination problems as it settles out on surrounding containers or on operators’ clothing. Therefore, while VLFs do create a very clean localised environment, they can, when used in conjunction with powder-weighing, actually contaminate a facility.
The clean booth is a powder/dust control system intended to capture dust with minimal risk to the powder that gives rise to the dust cloud.
With conventional dust capture systems (sometimes called “local exhaust hoods”), dust capture is dependent upon a single force, namely exhaust air movement. This movement of airflow from the workroom into the exhaust system can be responsible for drawing contamination over the materials and ingredients being handled. For example, cross- contamination from surrounding materials, contamination from previous waste or even operator-borne contamination may all become airborne and pass through the powder-handling zone and over the products being weighed.
Another critical shortfall of this old technology is the sensitivity of local exhaust hoods to distance. At the proper design position, the distance between the exhaust hood and the dust source is correct and allows effective capture of dust without excessive product loss. However, any increase in the distance between the hood and dust cloud to twice the norm can see the effective capture fall as low as 5% of design specifications.
Unlike local exhaust hoods, the clean booth system provides two complementary dust-capture forces to ensure a more effective and safe dust capture. Clean booths generally have a combination of overhead vertical laminar airflows over the work zone. The laminar flow provides two benefits: first, the laminar airflow will assure a cleanroom quality environment (typically between “class 10,000′” to “class 100”) around the materials to be handled; and secondly, the vertical laminar flow ensures that the entire area of the clean booth is filled with a moving airflow that entrains airborne dust clouds, irrespective of position.
The supply airflow set up by the vertical laminar flow travels at approximately 0.5m/s, vertically through the height of the clean booth until it meets the second capture force. At low levels across the width of the clean booth an exhaust intake evacuates captured dust and laminar air at high velocity. This exhaust flow, travelling at 2–3m/s, captures dust clouds effectively over a distance of around 700mm. This is a far greater distance than is attainable with local exhaust hoods.
The key to the very high dust-capture ability of the clean booth lies in its relatively high airflows. A typical exhaust hood employs an exhaust volume of around 0.2–0.4m(3)/s. By comparison, a typical 2.5m clean booth will recirculate an exhaust flow of 2.5–3.0m(3)/s. This high air-change rate utilises two dust control forces: gentle laminar supply air from above, and high-velocity, low-level exhaust. In practice it has been found to be beneficial to position additional high-velocity exhaust grilles above/behind bulky dust-generating sources, such as IBC bins and milling machines.
The majority of clean booths utilise recirculatory airflows due to their high air-volume requirements. This means that high-quality filtration is essential in order to safeguard against accidental recirculation of therapeutic materials.
Clean-booth materials’ management
The starting point for any powder-dispensing project is to analyse the flow of materials and personnel, to provide optimum routing and minimise any risks of cross- contamination. Traditionally, dispensing clean booths have been formed as a “cul-de-sac” off the main workroom, with the objective of containing airborne dust within the clean booth.
The disadvantages of such traditional designs are associated with material flow, as both raw and dispensed materials can come into close contact. The operator’s own access is often difficult, due to the congestion of drums and materials awaiting his/her attention. From an overall flow perspective, traditional “cul-de-sac” dispensing clean booths are problematic and may, therefore, limit the scope for future upgrades, such as automatic storage and retrieval systems, as well as other automation devices.
The alternative to “cul-de-sac” clean booths is the “cross-flow” concept. Cross-flow material dispensaries are becoming increasingly popular, as this design positions the dispensary room as a “barrier” between the warehouse and production facility. Pressurised corridors are often used to provide a pressure-gradient to alleviate warehouse contamination entering the main facility.
Two main types of cross-flow systems are common: first, the pallet-entry-capable (PEC) clean booth; and secondly, the drum-entry-capable (DEC) clean booth. As the terminology suggests, the PEC setup permits a pallet load of materials to be entered, which permits a degree of flexibility in the handling of containers, both large and small. The DEC dispensary is perhaps the most technically advanced design, wherein roller tracks, or other conveying methods, convey a single raw materials container from the warehouse to the weighing area. The drum is then returned to storage after the weighing of empty batch containers, which are positioned onto a scale-mounted conveyor track and are then guided into the production facility after weighing and labelling.
The key advantages of the drum-entry-capable design are:
- No pallet entry within the dispensing clean booth, thus eliminating pallet damage.
- Ease of upgrade to future automation systems.
- Ease of upgrade to higher-containment design by implementing partial or complete barrier isolation between operator and materials.
The overall facility layout, and the process operations involved within the facility, will determine which of the three classic dispensing room layouts is best suited.
Irrespective of whether one selects a “cul-de-sac” or “cross-flow” design, consideration should be given to clean-booth specialisation.
High-volume excipients that require dispensing into 50 or 100kg lots involve considerable operator-exertion. Bag or drum transfer of such materials can be greatly improved by the incorporation of a drum/bag lifter or tipper.
For even larger volumes, the excipient clean booth may be set up for vacuum transfer via an air-swept screen, within which an overhead weigh-hopper and automated discharge system may be used to fill drums or intermediate bulk container (IBC) bins in a hygienic and dust-free manner.
The clean-booth system is a widely accepted powder- handling dust-containment solution within the international pharmaceutical industry. When provided by an experienced contractor, the clean-booth system will usually be provided in conjunction with site validation installation qualification/ operational qualification, dust-level monitoring to a pre-agreed, guaranteed level, and almost always with thorough operator-training to ensure that work practices and standard of operating procedures are all geared to minimise any potential cross-contamination. The clean booth is widely accepted by the FDA and MCA, as well as other regulatory authorities, as a valuable tool for preventing dust-escape and cross-contamination of sensitive pharmaceutical materials.