ReinRaumTechnik 3/2015 Englische Ausgabe:
During the emerging of aseptic processing the objective was to create isolators to minimize the product risk in a way that the operator was separated from the critical zone. With help of Restricted Area Barrier Systems, isolators or RABS, it is possible to reduce an intervention.

A major source of pollution in aseptic manufacturing is personal handling. Therefore, the reduction of human interventions in the critical zone leads to higher purity in the products. For aseptic manufacturing in pharmaceutical processing, Restricted Access Barrier Systems (RABS technology) as well as isolators offer improved sterility assurance for the product and an efficient protection of the staff against risks caused by hazardous substances. These aseptic barrier systems fulfill many applications in pharmaceutical production lines, such as finish manufacturing and packaging.

RABS: Solution for Flexible Handling
Isolators include an automated bio-decontamination system and are suitable for long-lasting campaigns. A RABS, on the other hand, is an appealing solution for cleanrooms and guaranties the quality needs for applications which require more flexibility. If necessary, a RABS can be opened to allow for process intervention, while the Isolators must be kept closed during the entire operation.
A major advantage of isolator technology over conventional cleanroom technology in aseptic environments is the high security level of protection of the product which is still not achievable with other methods working with aseptic products.
A RABS provides separation by the barrier on the basis of a closed system for processing, which reduces the risk of contamination of the product because of reduced contact surfaces in comparison with handling in a normal cleanroom. In other words: It contains a barrier system with HEPA-filtered air flow, which allows a faster start and handling of processes compared with isolators and more flexible changes. Also, remodelling and renovations are cheaper.
RABS air handling units operate similar to laminar flow fume hoods in a way that they get clean air from fan units through HEPA filters and the air vents from the unit into the RABS (overpressure airflow). Air exits through openings into the environment at a low level on the equipment. During operation, there should be no reason to open the RABS doors. If there is a severe cause to open the doors, the laminar air flow system and other elements must be able to prevent a collapse of the ISO 5 conditions. Each opening of the doors will be considered as a serious intervention and must be documented.
An open RABS enables measurements and monitoring. RABS can – similar to an isolator – be driven as doors close system, with a very low risk of contamination. But a RABS contains not only a clean air maintenance system, it also includes an air lock zone, a well-designed equipment, laminar air flow, ISO 5 conditions in the critical zone, a quality system in place, SIP (sterilization in place), standard opterating procedures for interventions, disinfection plans and a documentation of all processes.

Isolators: Solution for Occupational Safety and Product Protection
An isolator is a closed system which has to perform two functions. It is a key control measure in preventing staff-exposure to cytotoxic substances, some of which may be carcinogens. It also has to protect the product from microbiological contamination during drug fabrication.
Overpressured or underpressured isolators are enclosed units which rely on a steady flow of filtered air during use supplying ISO 5 conditions. Air entering and leaving the isolator will do so through HEPA filters. Access to an isolator is performed through glove ports and sterile transfer systems. Isolators can work in an ISO 5 to ISO 8 environment.
Cleaning can be done manually or automated. Bio-decontamination of the isolator occurs through an automated cycle with H2O2 decontamination. Should there be a leak of the isolator, the system is not airtight. For an overpressure system, the leak will allow air, which might be contaminated with cytotoxic substances, to enter the workplace. For a negative pressure system, air that may contain bacteria could enter the isolator and contaminate the preparation.
A good leak detection system should therefore be in place in order to ensure that the leak is identified by once. It is included in an environmental monitoring system with built-in sampling ports.

Comparison of Isolators and RABS
Compared to isolators, RABS guarantee for a faster start ups and easy change procedures. They offer more operational flexibility and reduced costs for validation processes.
On the other hand, isolator air handling requirements are more complicated because the air is recirculated, requiring return fans and piping. In order to maintain an overpressure, the air handling unit must be absolutely leak-tight.
Differences in cleaning and bio-decontamination for RABS and isolators also concern cleaning routines. RABS typically undergo manual cleaning, or a CIP system (cleaning in place) can be used after a manual clean-up of resources. Isolators are decontaminated automatically with hydrogen peroxide. A validation of the manual cleaning procedures in RABS is more challenging than an automated cleaning cycle of a CIP system as in isolators.
Isolators are a good choice for small facilities and provide significant investment reductions and operational cost savings. Gowning costs and expenses for Lab and maintenance are reduced.
The implementation of an advanced aseptic processing technology also includes an appropriate surrounding building and room design, including HVAC and air handling systems. Suitable disposal procedures for decontamination waste are also to be kept in consideration. What’s more, the building system utilities can have an impact on isolator pressure control plans.
A continuous monitoring system is an absolute must for the qualification process. Supervisors should also have a look on proper gowning procedures, training of the personnel in current good manufacturing practice (cGMP), SOP`s for interventions, and documentation protocols. These routines must be instituted and consistently evolved.