As Blow-Fill-Seal (BFS) manufacturing technology grows in popularity, pharmaceutical and biologics companies are forced to consider new challenges around cleanliness.
A blow-fill-seal (BFS) aseptic manufacturing process combines multiple critical steps of drug manufacturing into one streamlined, automated system. The first step of a BFS process is when plastic or glass material is extruded into a mold, forming a single-dose container. Next, the liquid drug product is filled into the container and then immediately sealed to the environment. This is all achieved in one integrated process without the need for human intervention.
Pharmaceutical and biologics companies are realizing the benefits of this technology. With BFS, drug dosing is more accurate, and risk of contamination by human intervention is mitigated. This technology has become increasingly more prevalent in the last 20 years as it is more recognized by regulatory agencies and the technology has improved. BFS manufacturing is expected to experience an annual growth rate of 8% between 2019 and 2029. The growth will be attributed to pharmaceutical companies, as well as other emerging therapy markets, such as biologics, that are conducting compatibility and stability testing with large molecule products.
As more companies integrate this process, they are tasked with the challenge of maintaining strict particulate and biological contamination controls. Although this process removes the risk of human contamination, forming the container in-line with BFS creates a new source of particulates when the material is extruded and cut. In other manufacturing processes, the container is formed offline and can be terminally sterilized by steam heat or EtO before it comes into contact with the drug. In a BFS process, combining these steps eliminates the opportunity to sterilize the container prior to filling.
A solution is to cleanse the containers with high-pressure sterile air after it is formed to evacuate any loose particulates. The production area where the sterilized drug product and the container are exposed to the environmental conditions is called the ‘critical area’. This area needs to maintain a high-quality level of sterility because the drug will not be sterilized again before reaching the patient. In the FDA’s Industry Guidance Document, Sterile Drug Products Produced by Aseptic Processing--Current Good Manufacturing Practice, the agency recommends placing a particulate counting probe near the critical area to take continuous air samples and implementing high-efficiency particulate air (HEPA) filters into their cleanroom conditions.
Blow-fill-seal technology is an exciting, and increasingly reliable, opportunity for the pharmaceutical industry. It is a testament, however, to the sentiment that even when technological innovation solves one problem, it also poses new challenges.