BFS technology can help maintain sterility during biologics manufacturing.
Blow-fill-seal (BFS) technology offers several advantages over other aseptic techniques, such as flexibility in packaging design, the ability to ensure a high level of sterility assurance, and keeping costs low (1). In addition, the use of BFS technology limits human involvement, further increasing the level of sterility assurance by completely eliminating important contamination factors in the process. The technology enhances the ability to form containers and closures during the packaging process, allowing for more bespoke designs of containers. Therefore, BFS technology can be used to meet specific needs and improve the ease of use of containers (1). To learn more about the logistics, benefits and potential drawbacks of BFS technology, Pharmaceutical Technology Talk to Dr. Waiken Wong, Development Engineering Manager at Woodstock Sterile Solutions, an Illinois-based aseptic development and commercial solutions provider.
Advantages of BFS Technology
Medical Technology: Can you explain what BFS packaging technology is and how it applies to bio/pharma manufacturing?
Wong (Woodstock Sterile Solution): Blow-fill-seal packaging is a method in which a container is formed, filled with product, and then sealed in an aseptic environment. What comes out is a completely sterile finished product. This is a good introduction to many drugs including biopharmaceuticals. Sterility is critical for biologics and many other pharmaceuticals because it prevents microbial contamination in the product.
Medical Technology: What are the advantages of BFS packaging technology compared to traditional glass vial manufacturing?
Wong (Woodstock Sterile Solution): Much less human intervention when packaging BFS [is employed], and humans are the biggest cause of pollution. Contamination can negatively impact microbial sterility. Because the BFS process takes place entirely within the machine’s cabinet, there is little possibility of external contamination and sterility issues. With BFS, the environment inside the machine cabinet is continuously monitored for the presence of live and non-live particles, and there is a constant, positive pressure spray of high-efficiency particulate air (HEPA) filtered air that covers the fill of the machine part. BFS machines. With these controls, coupled with the automation of the BFS machine, the operator doesn’t have to be in the room. It is designed to run on its own without any human intervention. Another benefit is that there are fewer components compared to glass bottles, so you don’t have to deal with stoppers, crimp caps and other closures. There is no equivalent cleaning step to glass bottles. There are also no equivalent processing steps that glass bottles need to go through, such as depyrogenation. Raw resin is used; it goes directly to the BFS machine and is directly molded. As a result, there are fewer components, fewer steps, and far fewer human interactions in the actual manufacturing process.
Medical Technology: Can you explain low temperature BFS and its benefits compared to regular BFS?
Wong (Woodstock Sterile Solution): Low temperature BFS requires the implementation of a combination of technologies in one manufacturing process to help control the heat transfer to the drug product. In a typical BFS process, there is naturally a fair amount of heat as the raw resin is being melted to make the bottle. The bottle itself also needs to be kept warm throughout the process in order to seal the container in the final step. There is latent heat, but Woodstock Sterile Solutions has found ways to control this heat so that biomolecules can survive unaffected by the manufacturing process. With the cold BFS process, you can package other medicines because you don’t have to worry about heat-sensitive medicines. Many biomolecules are heat-sensitive, and there are many proteins that can be denatured or degraded by heat, so the biopharmaceutical industry has traditionally moved away from BFS and stuck with glass—a tried and true choice. Having a collection of these manufacturing steps expands the possibilities for pharmaceuticals in blow-fill-seal.
Implement BFS technology
Medical Technology: What are the key considerations when implementing BFS technology?
Wong (Woodstock Sterile Solution): An important consideration is understanding the compatibility/interaction of pharmaceuticals with plastics. Before choosing a BFS, you need to understand how the product interacts with plastics – for example, if adsorption or absorption is a concern. Additionally, plastic containers are not permeable to glass, so it is critical to understand whether this will have an impact on the product’s overall shelf life. Having said that, there are ways to fight permeation, whether it’s water vapor moving out or oxygen entering, to maintain the quality of the product inside. Finally, while BFS can be used to fill high viscosity liquids, filling with BFS becomes difficult if the product is more like an ointment. This makes getting through pipes and other parts of the system more difficult, but the technology can handle a wide range of viscosities.
Medical Technology: What, if any, are the disadvantages of using BFS technology?
Wong (Woodstock Sterile Solution): The aforementioned permeability is a challenge, as is the material interaction I mentioned. Also, there are challenges with heat sensitive and heat sensitive products, but these can be solved using cold BFS.
Medical Technology: What are the regulatory and compliance considerations (if any) when using BFS?
Wong (Woodstock Sterile Solution): The FDA recognizes BFS as an advanced aseptic manufacturing technology for its ability to reliably manufacture sterile drug products while ensuring a high level of quality for patients. Like all pharmaceutical packaging technologies, the industry follows the same standards to ensure product safety and quality.
S. Bondre et al., ARPB 3 (4) 494–499 (2013).
About the author
Alivia Leon is Pharmaceutical Technology, European Pharmaceutical Technologyand Biopharma International.
full. 46, no. 9
Pages: 37, 51
When citing this article, please cite A. Leon, “Improving Sterility Using the Blow-Fill-Seal Technique” Pharmaceutical Technology 46 (9) 37, 51 (2022).