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BFS technology can help maintain sterility during the biologics manufacturing process.
Blow-fill-seal (BFS) technology presents several advantages over other aseptic techniques, such as flexibility in packaging design, the ability to ensure a high level of sterility assurance, and maintaining low costs (1). In addition, the use of BFS technology limits human involvement, which further improves the level of sterility assurance by removing a significant contamination factor from the process entirely. The technology enhances the ability to form the container and closure during the packaging process, which allows for a more custom design of the container. BFS technology can thus be used to meet specific needs and improve container ease-of-use (1). In order to learn more on the logistics, benefits, and potential drawbacks of BFS technology, Pharmaceutical Technology spoke with Waiken Wong, PhD, manager of development engineering at Woodstock Sterile Solutions, an Illinois-based provider of sterile development and commercial solutions.
PharmTech: Can you please explain what BFS packaging technology is and how it applies to bio/pharmaceutical manufacturing?
Wong (Woodstock Sterile Solutions): Blow-fill-seal packaging technology is a method where the container is formed, filled with product, and then sealed in a sterile environment. What comes out is a fully sterile finished product. It’s a good presentation for many drugs, including biopharmaceuticals. Sterility is critical for biologics and many other drugs because it prevents microbial contaminants in products.
PharmTech: What benefits does BFS packaging technology offer, compared to traditional glass vial manufacturing?
Wong (Woodstock Sterile Solutions): There is far less human intervention when BFS packaging [is employed], and humans are the biggest cause of contamination. Contamination can have a negative impact on microbial sterility. Because the BFS process happens completely inside the cabinet of the machine, there is little chance for external contamination and problems with sterility. With BFS, the environment inside the cabinet of the machine is continually monitored for viable and non-viable particulate, and there is a constant, positive pressure shower of high-efficiency particulate air (HEPA)-filtered air that covers the filling section of the BFS machine. With those controls in place, along with the automation of the BFS machine, the operator doesn’t have to be in the room. It is designed to operate on its own, without any human intervention. An additional benefit is that there are fewer components compared to glass vials, so you don’t have to deal with stoppers, crimp tops, and other closures. There are no equivalent cleaning steps to the ones glass vials need to go through. There are also no equivalent treatment steps to the ones glass vials need to go through, such as depyrogenation. Raw resin is used; it goes directly into the BFS machine and is molded directly. So, there are fewer components, fewer steps in the actual manufacturing process, and there is far less human interaction.
PharmTech: Can you explain cold temperature BFS and its benefits compared to regular BFS?
Wong (Woodstock Sterile Solutions): Cold temperature BFS requires implementing a combination of techniques all together in one manufacturing process to help control the amount of heat that is imparted onto a drug product. During the typical BFS process, there is naturally quite a bit of heat, because raw resin is being melted to make bottles. The bottles themselves also need to be warm throughout the process so that the containers can be sealed shut in the final step. There is latent heat, but Woodstock Sterile Solutions has found ways to control that heat so that biomolecules can survive with no impact through the manufacturing process. With a cold BFS process, there are additional drug products that you can package, since you do not have to worry about drugs that are thermally sensitive. Many biomolecules are heat sensitive, and there are many proteins that can denature or degrade with heat, so traditionally, the biopharma industry has stayed away from BFS and stuck with glass—a tried-and-true option. Having this collection of manufacturing steps expands what is possible for drug products in blow-fill-seal.
PharmTech: What are some key considerations when implementing BFS technology?
Wong (Woodstock Sterile Solutions): One important consideration is understanding the drug product’s compatibility/interactions with plastic. Before opting for BFS, there needs to be an understanding of how the product interacts with plastic—if there are concerns about adsorption or absorption, for example. Additionally, plastic containers are permeable in a way that glass is not, and it is critical to understand if that will have an impact on the product throughout its shelf life. That being said, there are ways to counter permeation, whether it is water vapor moving out or oxygen moving in, in order to maintain the quality of the product inside. Lastly, although BFS can be used to fill liquids that are highly viscous, if the product is more ointment-like, then it will be difficult to fill using BFS. That makes it harder to push through the piping and other parts of the system, but the technology can handle a wide range of viscosities.
PharmTech: What are the drawbacks of using BFS technology, if any?
Wong (Woodstock Sterile Solutions): The permeability mentioned earlier is one challenge, as are the material interactions I noted. Also, there are challenges with heat and thermally sensitive products, but those can be addressed using cold BFS.
PharmTech: What are the regulatory and compliance considerations when using BFS, if any?
Wong (Woodstock Sterile Solutions): FDA considers BFS as an advanced aseptic manufacturing technique, recognizing its ability to produce sterile drug products reliably while also ensuring a high level of quality for patients. The industry is held to the same standards, as all drug packaging technologies are, to ensure product safety and quality.
S. Bondre, et al., ARPB 3 (4) 494–499 (2013).
Alivia Leon is an assistant editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International.
Vol. 46, No. 10
Pages: 37, 51
When referring to this article, please cite it as A. Leon, "Improving Sterility Using Blow-Fill-Seal Technology," Pharmaceutical Technology 46 (10) 37, 51 (2022).