Appropriate guidelines, manuals, and drafts for isolators are available in the three major pharmaceutical markets: the United
States, Europe, and Japan. The recently rewritten FDA guidelines, Annex 1 of the European Union good manufacturing practice
guidelines, and the detailed PIC/S recommendations are helpful for the planning and use of an isolator (3, 4, 8). The Japanese
admission authority also is presently working on an appropriate document.
Classifications of RABS
RABS are more than just a safety covering for production machines. Incoming air passes through suspended high-efficiency (of
at least HEPA Class H14) filters and is distributed evenly by a sterile manifold. The doors of the RABS are locked, and the
gloveports are the only means of access. Users must transfer materials and components by means of special aseptic transfer
systems. Air flows out of RABS the same way it does with simple barriers: through openings underneath the doors or through
holes in the lower sections of the doors. The air returns to the same room from which it came. In a closed RABS, air is prefiltered
and recirculated through ducts.
Figure 4: Machine in an active RABS. The RABS has its own air-handling system that draws air from the area and through openings
below the product transport.
RABS can be classified as either active or passive systems. A passive RABS does not have its own air recirculation, filtering, or conditioning. Its high-purity air supply comes from the cleanroom.
Air flows downward from the ceiling and returns to the surrounding room through openings under the doors. The air from the
room returns through air ducts to the room air-handling unit (see Figures 3 and 4).
An active RABS typically has an air-handling unit directly attached to it. This unit always contains a HEPA filter and provides even
air-flow distribution with the help of a sterile air manifold. A cooling system also can be integrated for temperature-critical
products. Air-conditioning expenditure is limited because fresh air is drawn from the cleanroom (see Figure 4).
Figure 5: Machine in a passive closed RABS. Air is recycled from the room air-handling system. A prefilter also is used, which
helps prevent contamination of the air-handling system.
A closed RABS is different. Closed RABS also may be passive systems that use the cleanroom's ventilation system and filter ceiling. The air does not return
to the surrounding area, it passes through prefilters and ducts into the room's airconditioning system (see Figure 5). Because
closed RABS concepts are used with toxic and dusty product applications, operators must pay special attention to cleaning
the return air ducts and changing the prefilters without contaminating them (see Figure 6).
Figure 6: Aseptic powder-filling line in passive closed RABS.
Active closed RABS have air-filtration and air-conditioning systems (see Figure 7), which are needed to keep conditions constant
within the aseptic area, especially when air cooling is required.