Product-contact parts.
The sterile assembly of filling-machine product-contact parts, including containers and component-holding parts, is difficult,
especially when the component size is considered. For example, after a production run, a stopper sorting bowl was cleaned,
dried, packed into a sterile bag, and autoclaved (e.g., in the material lock). Afterwards, the packaged bowl was taken from the air lock. The bowl was unpacked outside the sanitized
RABS because of its physical dimensions. The heavy and bulky sorting bowl subsequently had to be installed into the aseptic
area through an open RABS door. The draft of the RABS definition states:
"Sterilization-in-place (SIP) is preferred for contact parts such as fluid pathways. Where this cannot be achieved, such parts
should be sterilized in an autoclave, transferred to the RABS via a suitable procedure and aseptically assembled before processing (6)."
Disinfection.
The sanitation of a RABS is substantially more complex than that of a machine with no barrier system. More surfaces and larger
surfaces must be sanitized, and some surfaces are harder to reach because of the barrier. Operators try to achieve aseptic
conditions with a RABS, which is impossible with open production systems.
The draft RABS definition refers to a "'high-level disinfection' of all nonproduct contact surfaces within the RABS with an
appropriate sporicidal agent before batch manufacture" (6). The draft defines high-level disinfection as a microbiological disinfection that increases product security and is a precondition for long production runs. A partition
between operators and aseptic production areas is insufficient for better product security. The correct interface solutions
and the correct handling are highly significant. RABS allow long production runs, but impose more restrictions than isolation
systems. The definition draft carefully states:
"In certain circumstances, multiple day operations are possible depending on design, appropriate disinfection plan, risk mitigation
steps, early regulatory review (i.e., pre-operational review is recommended), and a subsequent ongoing evaluation of process control data (6)."
To avoid an open-door intervention, the machine function should be highly automated and as reliable as possible. Each intervention
risks contact contamination or the ingress of low-quality outside air. For this reason, a RABS should have an automatic clean-in-place–steam-in-place
(CIP–SIP) system as an isolator does. This system prevents manual handling of product-contact parts such as pumps and filling
needles. The draft RABS definition supports this in the following passage:
"Design to prevent door openings can be achieved by a number of measures which include Clean-In-Place/Sterilize-In-Place
(CIP/SIP) to the point of fill for liquid filling operations, remote or automated sampling for in process control testing
(IPC) including monitoring for viable and non-viable particles, and the use of enclosed transfer systems which offer greater
protection during introduction of components and pre-sterilized equipment (6)."
Closed RABS
Figure 9: Mousehole in active closed RABS.
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Closed RABS are a special case because they take both aseptic requirements and industrial safety into account. The draft RABS
definition states, "There are occasions where containment of toxic materials is required and special closed or containment
RABS may be used" (6). Recirculating air must be prefiltered in a closed RABS before it returns to the air-recycling system.
Prefilter changes must occur either under full protection or through a contamination-free procedure (i.e., bag-in–bag-out). Pressure-isolation zones, or pressure buffers, can protect upstream and downstream equipment from filling-area
contamination. Implementing pressure zones, however, requires sealing the closed RABS sufficiently and separating the pressure
zones with mouseholes (see Figure 9).
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