Pharmaceutical Aseptic Processing-Barrier Systems

Barrier Systems

Barrier systems are physical controls put in place to prevent contamination in pharmaceutical manufacturing cleanrooms.

There are 2 types of barrier systems used which are Restricted Area Barrier System (RABS) and Isolators

Restricted Area Barrier System (RABS)

These are physical barriers in aseptic processing used to physically separate operators from sterile product during manufacturing.

Inside RABS, cleanroom grade is always grade A and surrounding environment should be grade B. A positive unidirectional airflow from the RABS critical zone to the surrounding environment should be maintained. This is to avoid contamination from surrounding environment

RABS uses a glove system which personnel uses to make contact with production. Glove integrity should be tested on timely intervals to ensure there is no tear or leakages. Testing gloves integrity include visual inspections regularly

Gloves should be sterile always and this means sterilizing them before installation and after every production batch.

Cleaning and Sterilization method used on gloves should not affect gloves integrity

Parts which comes into contact with product should be sterilized and aseptically assembled prior processing. After processing, these parts should be cleaned and sterilized. In-Place-Sterilization is preferred for most parts, but if it’s not feasible, the parts can be disassembled cleaned and sterilized

Cleaning and bio-decontamination of RABS should be performed at regular intervals using a method that has been validated.

In some cases where the RABS doors are opened, extra caution should be taken to prevent contamination. These include always maintaining a positive airflow from RABS to surrounding environment.

Each time the RABS doors are opened, it is important to document that down and the purpose for opening the doors

Isolators

Isolator is a totally enclosed stainless steel equipment. There are 2 types of isolators which are used, which are open isolators and closed isolators. Open isolators do have a breach which allow for transfer of material.

Mainly open isolators are found in grade C cleanrooms. Closed isolators are sealed system which offer maximum containment and protection from contamination. Closed isolators are found in cleanroom grade D

Isolators are mainly used in containment of hazardous material which maybe harmful to personnel or environment OR aseptic filling of potent material

Isolators, depending on design can have positive airflow or negative airflow. Positive airflow is used to prevent surrounding environment from contaminating the aseptic process in the isolators.

Negative airflow is used when there is hazardous material inside isolators which might spread into surrounding environment and cause harm to personnel or environment

Isolators systems make use of gloves system as well. I t is important to ensure glove and glove port integrity by performing regular inspection upon installation and after production batch. The inspections should be performed at predetermined intervals

Bio-decontamination of Isolators should be automated and validated that occurs at determined intervals. One of the automated bio-decontamination method used in Isolators is use of vaporized hydrogen peroxide. This method is easily automated, repeated and validated, thus making it easy to achieve the set Sterility Assurance Level (SAL).

Robotics In Aseptic Processing

Robots are now being integrated into these barrier systems to improve quality of products. Since the aseptic process is mainly repetitive, robots can be programed to perform the set task with higher accuracy and greater speed than a human could. This increases product output, saves time and reduces human errors.

With the advancement of Artificial Intelligence and Automatic Robot Tool Changer Technology, we will see a future where robots take on more roles in the aseptic manufacturing processes to the extent of completely running the whole manufacturing with little or no personnel intervention

Read Also

Annex 1 Manufacture of Sterile Medicinal Products EudraLex Volume 4(EU 2022)

Restricted Access Barrier Systems (RABS) & Isolators: The Perfect Combination of Robot System Safety and Aseptic Drug Manufacturing by Joshua Russell (2010)