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8 Definition of restricted access

barrier systems
Jörg Zimmermann

INTRODUCTION
RABS—restricted access barrier systems—were developed to advance the aseptic processes that
were previously carried out in conventional clean rooms.
Traditionally, the protection of product from contamination by the operator was achieved
by putting the filling equipment under laminar airflow units. Manual interventions, operators
operating directly over open product, uncontrolled airflow patterns and frequent sterility test
failures, and media fill failures were common then.
It was widely acknowledged that the concept of isolators for aseptic filling was nearly
immediately understandable, while the design concepts and ways of operation for RABS
were somewhat more difficult to understand. Several attempts were made to exactly define
RABS, some of them creating perhaps more confusion than actually helping to understand the
technology.
In 2005, triggered by a request from the US Food and Drug Administration, a group
of industrial professionals within ISPE (International Society of Pharmaceutical Engineering)
worked out a concise definition of RABS (1). The main building blocks of this definition were
the following:

r Rigid wall enclosure

r ISO 5 unidirectional airflow environment
r Gloves for set-up and interventions
r Automation of the process wherever possible
r Sterilization of all equipment
r High-level disinfection (i.e., sporicidal disinfection)
r Rare open-door interventions

The open-door interventions need to be under a defined protocol with line cleaning/line
clearance and local sanitization. The appropriate documentation for this intervention is also
mandatory. When this definition was published, the debate continued on the inclusion of “rare
open-door interventions.” This was seen as a way out of proper aseptic technology, allowing
for inclusion of bad practices.
In this chapter, an attempt is made to define the different variants of RABS in a more
appropriate manner.

Passive RABS–Active RABS

The terms “passive” and “active” RABS refer to the way in which the RABS air supply is
designed within the core aseptic area. Generally, a passive RABS has air supply through HEPA
filters that are part of the clean room (Fig. 1) (2).
For a passive RABS to work properly, the HEPA-filter surface has to be larger than that of
the machine. This is due to the open space between the top of the machine cover and the filter
surface. If this is fully aligned, air ingress from class B cannot be avoided due to the Venturi
effect.
An active RABS has air supply through HEPA filters, which are integrated into the ceiling
of the machine barrier (Fig. 2) (2).
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HEPA filters
3–6" From
HEPAS

Filling
Class 10,000 Class 100 mechanism
(ISO 7) (ISO 5)

Nozzle

Vial

Conveyor

Figure 1 RABS (Passive) Restricted Access Barrier System. Source: From Ref. 2.

HEPA

HVAC

HEPA filters

Class Filling
Class 100 mechanism
10,000
(ISO 5)
(ISO 7)

Nozzle

Vial

Conveyor

Figure 2 RABS (Active) Restricted Access Barrier System. Source: From Ref. 2.
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78 ADVANCED ASEPTIC PROCESSING TECHNOLOGY

Closed RABS
HEPA

HEPA Filters

Class Filling
10,000 mechanism
(ISO 7)

Nozzle

Vial

Conveyor

Air
return

Figure 3 RABS (Closed) Restricted Access Barrier System. Source: From Ref. 2.

Open RABS–Closed RABS

The terms “open” and “closed” RABS refer to the manner in which the airflow at the bottom
of the machine is designed. An “open” RABS therefore is a RABS where the air spills over into
the room and is recirculated into the room heating, ventilation and air conditioning (HVAC)
system through central return air channels.
A “closed” RABS has the air recirculated into the HVAC system that is part of the machine.
Air overspill into the room is avoided through hermetic seals. This brings a closed RABS almost
to the level of an isolator, but usually without automatic decontamination (Fig. 3) (2).

RABS for Containment

A RABS used for the filling of highly potent drugs where operator protection becomes equally
important as product protection can be designed by adding clean-in-place equipment.
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DEFINITION OF RESTRICTED ACCESS BARRIER SYSTEMS 79

Operation of a RABS
All of the above-mentioned RABS variants can be operated as a best-practice RABS
where open-door interventions are strictly prohibited. When this is combined with frequent
high-level disinfection, proper aseptic technique and monitoring, a very safe and robust pro-
cess is achieved.

CONCLUSIONS
As always, product requirements, dosage forms, and economic considerations have to be aligned
when a new filling room is designed. Following the original ISPE–RABS definition and combin-
ing it with the simple distinctions between active/passive and open/closed RABS, one should
easily come to the right conclusions as the design and operation of RABS.

REFERENCES
1. Lysfjord J, et al. Restricted access barrier system (RABS) for aseptic processing. Pharm Eng 2005;
25(6):116–117, 120.
2. Lysfjord J. Aseptic Processing: Advancements in Manufacturing—RABS & Isolators. PDA Conference
on Risk Management, Bethesda, MD, May 15–16, 2008.