Achieving Liquid Process Quality with Aseptic BFS Technology
By Chuck Reed, BSc/MS
Director, Sales and Marketing, Weiler Engineering Inc.
Blow-fill-seal (BFS) aseptic processing has established itself as a highly efficient and safe system to fill and package sterile pharmaceutical liquids and other healthcare products, such as creams and ointments.
The inherent safety of the process—packaging sterile products under aseptic conditions without human intervention—has led FDA and the United States Pharmacopeia to characterize BFS technology as an “advanced aseptic process,” indicating its use as a preferred technology.
|Aseptic BFS technology could protect patients from contaminants.|
In the advanced aseptic BFS process, containers are formed from a thermoplastic granulate, filled with a liquid pharmaceutical product, and then sealed within a continuous, integrated, and automatic operation without human intervention. Bulk solution prepared under low bioburden or sterile conditions is delivered to the machine through a system that has been previously sterilized using an automated steam-in-place process.
The forming, filling, and sealing steps are achieved in one automatic unit operation—the cycle being completed within seconds. Automation of BFS process steps eliminates manual intervention and reduces risk to the product. No production personnel are present in the filling room during normal operation.
The sterility of BFS polymeric containers, materials, and processes is validated by verifying that the time and temperature conditions of the extrusion, filling, and sealing processes are effective against endotoxins and spores.
A critical aspect of BFS technology is that it molds containers and ampules without pyrogens, which can lead to serious reactions in patients, particularly through injections. Extensive experiments confirming the efficacy of the BFS extrusion process have been performed using high levels of spores and endotoxin-contaminated polymer granules. The typical BFS extruders have demonstrated spore contamination rates of 0.000001%, and 0.00001% for endotoxins.
BFS equipment design typically uses specialized measures to reduce microbial contamination and particle levels that can contaminate the exposed product. Provisions for carefully controlled airflow protect the product by forcing created particles outward while preventing any inflow from the adjacent environment. These can also incorporate designs that separate them from the surrounding environment, providing additional product protection.
The BFS critical processing zone is continually supplied with HEPA-filtered air by an air shower device (shroud). The BFS critical zone is the area where the containers are exposed during filling. Air in the critical zone meets Class 100 (ISO 5) microbiological standards during operations. The critical zone is continuously monitored to ensure a positive differential pressure is maintained between the shroud and the adjacent cleanroom.
Many BFS machines are configured to produce more than one bottle shape or format. This simplifies changeover from one container size to another. A BFS machine might produce a family of 2, 3, and 5 ml, then switch to a family of 5, 10, and 15 ml, moving from one to the other with relative ease of machine setup. This is ideal for manufacturers performing contract packaging of aseptic liquid pharmaceutical solutions, because of their need for changeover flexibility.
Growing use of biologics demands packaging in different formats. They usually require smaller process runs and are typically heat sensitive. Many do not withstand steam sterilization or irradiation and so are best treated aseptically. More-advanced BFS machines have been designed so they can handle these heat-sensitive products.
These advances are significant, if not fully realized yet within the aseptic liquid pharmaceutical marketplace. But it is apparent that advanced BFS aseptic technology is destined to become a major player in this arena. ■