Go with the flow

Increasingly, materials used in the modern pharma industry pose a health danger to operators involved in the production process. But clean booth containment technology can reduce the risk

Regulatory compliance factors and GMPs in today's pharmaceutical industry stipulate that production must be conducted in a safe, contamination-free environment. But aside from the product quality issues that ineffective powder and environmental control can cause, there is growing concern that many materials being handled in today's pharmaceutical industry may cause severe health risks to those operators involved in direct production operations.

The use of so-called 'potent compounds' is increasing at an alarming rate. In 1990 only 5% of all solid dosage form materials were considered potent, but by 2000, 35% or more of all materials handled were considered potentially harmful to operators. Certain compounds now in use are sufficiently active to cause irreversible operator sensitisation after only a single exposure. With these very real threats to product quality and operator health many pharmaceutical manufacturing organisations are turning to containment technology to provide solutions.

One of the most critical areas in a solid dosage form plant 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.

It is important to dispel the belief that vertical laminar flow modules (VLFs) provide a safe method of controlling the environment during powder dispensing and weighing. VLFs will provide a clean environment over certain work operations and are generally intended to provide a localised class 100 environment around critical areas, such as syringe filling. However, they should never be confused with a true clean booth for powder weighing.

cross-contamination risk

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 specifically developed for use in the pharmaceutical sector. This technology is 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 depends on a single force, namely exhaust air movement. Room air around the work area (drums or weigh-scale) is accelerated to a capture velocity, which can be as high as 2m/s. This high velocity airflow will capture airborne dust and then sweep the captured material into the exhaust hood and extraction pipeline for collection in the filtration system.

But 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 conventional 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, due to the fact that any suction opening induces air from all directions – even from behind in the case of a freestanding hood. This unfocused flow means that the system designer has to engineer a hood that will concentrate the exhaust airflow from the desired position.

Nevertheless, the physics of air flow will never permit effective capture of a dust cloud unless the exhaust hood is correctly positioned, making dust capture systems with adjustable hoods highly dependant upon the operator – and hence, in many cases, ineffective.

Unlike local exhaust hoods, the clean booth system provides two complementary forces to ensure a more effective and safe dust capture. Clean booths generally have a combination of overhead VLFs over the work zone. The laminar flow provides two benefits: first, it will assure a cleanroom quality environment (typically between class 10,000 and class 100) around the materials to be handled; and second, the VLF 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 – far more 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 0.2-0.4m³/s, whereas a typical 2.5m Clean Booth will recirculate an exhaust flow of 2.5-3.0m³/s.

combination of forces

This high air change rate uses a combination of two dust control forces – gentle laminar supply air from above, and high-velocity, low-level exhaust. In practice it has proved 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 use recirculatory airflows due to their high air-volume requirements. This means that high quality filtration is essential to safeguard against accidental recirculation of therapeutic materials. In 1989 Extract Technology conducted a material recirculation and dust-egress test on a simple two-level filtration clean booth, in response to QA concerns. The test was conducted using micronised acetaminophen powder, which was dispensed back and forth within a 2.0m clean booth over a 5-day period. In all, around 1000kg of powder was transferred during the test period, after which pre-determined swab sites were analysed using sterile throat swabs and an HPLC assay method.

The data was analysed by a QA expert, and the system was qualified as not creating a cross-contamination risk . The 1989 test clean booth featured terminal HEPA filters with EU8 filtration only, ahead of the pressurised plenum chambers. From a reliability standpoint, it has been found to be beneficial to mount both EU8 and HEPA filters on the negative pressure side of the fan, with non-filtration distribution screens in the clean booth ceiling. Some clients elect to place a second or 'redundant' HEPA filter beyond the fan to trap contamination in the event of bearing failure. This second HEPA filter also provides a valid back-up to the main HEPA filters.

Some concerns have been expressed about the life expectancy of the filtration elements fitted to clean booths, as opposed to local exhaust hoods, which use low volume, high-velocity airflows and collect valuable product powder. The clean booth, with its high-volume sweeping airflows, collects only around 0.1% of weighed material. This low level of product powder pick-up means that the pre-filters can last 3-9 months, and the HEPA filters have a typical life of 4-6 years.

Another benefit of the low levels of powder collection is the minimised risk of dust explosion. In a well-designed clean booth the ratio between contaminated (soiled) filter volume and the open-pressure venting area means explosion venting is unnecessary. In contrast, dust collectors associated with local exhaust hoods must be explosion-vented or fitted with explosion-suppression systems.

The starting point for any powder-dispensing project is to analyse the flow of materials and personnel in order to provide optimum routing and to minimise any risk of cross-contamination. Traditionally, dispensing clean booths have been formed as a 'cul-de-sac' off the main workroom, with the aim of containing airborne dust.

limited scope

The disadvantages of such traditional designs are that both raw and dispensed materials can come into close contact, while the operator's own access is often difficult, due to congestion from drums and materials. Traditional 'cul-de-sac' dispensing clean booths may therefore limit the scope for future upgrades, such as automatic storage and retrieval systems, and other automation devices.

The alternative to 'cul-de-sac' clean booths is the 'cross-flow' concept. Cross-flow material dispensaries, which position the dispensary room as a 'barrier' between the warehouse and the production facility, are becoming increasingly popular. 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. The pallet-entry-capable (PEC) clean booth permits a pallet load of materials to be entered, which offers a degree of flexibility in the handling of both large and small containers. But the drum-entry-capable (DEC) clean booth is perhaps the most technically advanced design, wherein roller tracks or similar convey a single raw materials container from the warehouse to the weighing area. The drum is 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 this design are:

The overall facility layout and the process operations involved will determine which of the three classic dispensing room layouts is the most suitable. But irrespective of whether a 'cul-de-sac' or 'cross-flow' design is selected, 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 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 for preventing dust-escape and cross-contamination of sensitive pharmaceutical materials.