Figure 7: Machine in active closed RABS. The RABS has its own air-handling unit. If necessary, recirculating air is prefiltered
over mechanisms that permit a contamination-free filter change.
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Closed RABS can be operated with positive or negative pressure, which requires good sealing and pressure control. In these
applications, a closed RABS is similar to an isolator (see Figure 8).
The next level of aseptic operation and production safety is not attainable with RABS because of the lack of a biodecontamination
system and the reduced air sealing. Closed RABS, as opposed to isolators, also require additional expenditures that must be
considered (e.g., the surrounding area must be an ISO class 7 cleanroom). Each RABS installation balances pharmaceutical security, industrial
safety, building support systems, operational flexibility, and the money invested in the system.
If the RABS is operated according to the guidelines, the component-transfer techniques, sanitation processes, format-change
procedures, and maintenance procedures required are different from those of a cleanroom installation.
Operating a RABS
Glove integrity.
Before the beginning of a production run, the integrity of the barrier must be guaranteed. In particular, the gloves must
be tested for leakage and damage regularly. To reduce dependence on SOPs, a regular physical testing method should be used
in addition to the visual examination of the gloves. Two options for examination are:
- testing the gloves before mounting them on the RABS and sterilizing them;
- testing the gloves in the mounted position.
Both options have advantages and disadvantages. When the gloves are mounted, the entire glove assembly, including the mounting
ring, can be tested. When the glove is tested before mounting, the isolator can be prepared for production, thereby reducing
setup time. The sterile installation of the gloves is a challenge in each case. The gloves must be pre-sterilized, transferred
into the cleanroom, and installed to the mounting ring in a sterile manner.
Figure 8: Active closed RABS with pressure-zone control.
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Glove sterilization can occur in an autoclave bag. The material of the glove is a key factor for sterilization. Common glove
materials such as chlorosulphonated polyethylene (Hypalon) will physically change after 8–10 cycles in an autoclave. More-stable
materials such as ethylene propylene diene monomer, however, are stable for a nearly unlimited number of cycles in an autoclave.
Assembling the gloves at the glove-mounting rings in a sterile way is difficult and requires experienced operators. Reversing
the mounting ring can facilitate this operation by allowing the glove to be mounted from outside the isolator, rather than
from inside. This arrangement reduces the length of the glove, however, so longer gloves may be necessary.
Sterile transfer.
Components, tools, and growth media for monitoring the microbiological state of the air in the RABS must be transferred in
a sterile manner. A RABS can incorporate systems such as double-door transfer and steam sterilizers. A transfer chamber or
simple transfer door also can be used. Transfer chambers possess inner and outer doors that are interlocked so that only one
door can be opened. The interior of the transfer container, from which components such as stoppers are taken out of bags and
introduced into the production process, should be ISO category 5. Simple transfer doors should be installed below the process
level to reduce the influence of ambient air on the aseptic area. Opening the main doors to transfer components is not permissible,
according to FDA's draft definition, because a RABS has no positive-pressure plan that could prevent outside air from entering
the system. Closed RABS can be operated with positive pressure, but opening the doors during operation is not permitted for
industrial-safety reasons.
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