Barrier Systems

Barrier system basics

Barrier System is a term generally used to describe a physical and aerodynamic barrier between the ambient clean room and the area where the fill- and closing process of the containers actually happens.

A history review

... and the approach to reach a higher SAL, by separating the operator from the drug.

Drug manufacturing in the 1950s-70s was far more prone to microbial contamination problems and the biggest source for contamination was identified as human intervention.

The fill-finish process therefore had to be examined more closely and solutions needed to be found to increase the Sterility Assurance Level (SAL).

First installations of passive open RABS were seen in the late 70s.

For better control of the airflow and to eliminate room design restrictions another evolutionary step was made towards active open RABS designs.

The early open RABS installations were not independent from ambient room conditions. Controlling the temperature at point of fill was not possible without influencing the room, so the time was set in the late 80s for first closed RABS installations, which came with their own air handling units. This made temperature, laminar-flow, humidity and pressure control independent from the ambient room.

The late 80s and early 90s also brought up isolator technology — a closed RABS design, but additionally to standard cleaning procedures with an integrated and automated sanitization process, for example VHP — Vaporized Hydrogen Peroxide.

RABS vs. Isolator

METALL+PLASTIC GmbH

Let’s start comparing the systems while in operation

All types of RABS are operated in ISO 7 / EU cGMP Grade B, while isolators are operated in ISO 8, which equals EU cGMP Grade C/D.

Isolators come in two different versions besides variants like closed and open systems.

There are isolators for standard products and containment isolators for toxic products. The design elements and processes are slightly different.

The focus of a containment isolator design is to protect the operators. For regular isolators, the primary objective is to protect the drug product.

What is different?

• Better leakage rate for containment isolators, for example 2% compared to 3% for standard isolators.
• The sealing / gasket is different on containment isolators because hazardous drug products are processed.
• Redundant sealing concept for doors and mouse-holes due to operator risk.
• Wash-down for containment isolator interior is needed before opening.
• Return air ducts if no point-of-use filters are in place.
• No isolator-to-room air recirculation possible; production exhaust air needs to go outside.
• Air can be taken from the room.
• Point-of-use return air filtration or Bag-in-Bag-out filters in recirculation / exhaust duct are needed.
• Different programming logic: in case of sterility loss, sealing issues, spills, leakage or malfunction, the system needs to evacuate the interior of the barrier system and switch to negative pressure, for example -5 Pa.

Aseptic risk reduction by raising sterility level

Increasing confidence level

Another advantage of closed systems — such as cRABS, isolators or containment isolators — is that the confidence level of safety in dealing with toxic substances is also increased.

Facts & Figures — Pros & cons at a glance

Summary

• Traditional clean room applications are becoming history.
• Isolators continue to gain a greater percentage of overall barrier applications.
• RABS systems are more and more treated like isolators.
• Regulators lean more and more towards isolators.
• The higher initial investment for an isolator can be covered well by lower running costs compared to RABS.
• The future brings more reduction / elimination of human intervention, gloveless systems and fully enclosed processes.