BFS expertise will help keep sterility through the biologics manufacturing course of.
Blow-fill-seal (BFS) expertise presents a number of benefits over different aseptic strategies, akin to flexibility in packaging design, the power to make sure a excessive degree of sterility assurance, and sustaining low prices (1). As well as, using BFS expertise limits human involvement, which additional improves the extent of sterility assurance by eradicating a major contamination issue from the method fully. The expertise enhances the power to kind the container and closure through the packaging course of, which permits for a extra customized design of the container. BFS expertise can thus be used to satisfy particular wants and enhance container ease-of-use (1). As a way to study extra on the logistics, advantages, and potential drawbacks of BFS expertise, Pharmaceutical Know-how spoke with Waiken Wong, PhD, supervisor of improvement engineering at Woodstock Sterile Options, an Illinois-based supplier of sterile improvement and business options.
Advantages of BFS expertise
PharmTech: Are you able to please clarify what BFS packaging expertise is and the way it applies to bio/pharmaceutical manufacturing?
Wong (Woodstock Sterile Options): Blow-fill-seal packaging expertise is a technique the place the container is shaped, stuffed with product, after which sealed in a sterile setting. What comes out is a completely sterile completed product. It’s an excellent presentation for a lot of medicine, together with biopharmaceuticals. Sterility is essential for biologics and plenty of different medicine as a result of it prevents microbial contaminants in merchandise.
PharmTech: What advantages does BFS packaging expertise supply, in comparison with conventional glass vial manufacturing?
Wong (Woodstock Sterile Options): There’s far much less human intervention when BFS packaging [is employed], and people are the largest reason for contamination. Contamination can have a detrimental affect on microbial sterility. As a result of the BFS course of occurs fully inside the cupboard of the machine, there’s little probability for exterior contamination and issues with sterility. With BFS, the setting inside the cupboard of the machine is frequently monitored for viable and non-viable particulate, and there’s a fixed, optimistic strain bathe of high-efficiency particulate air (HEPA)-filtered air that covers the filling part of the BFS machine. With these controls in place, together with the automation of the BFS machine, the operator doesn’t need to be within the room. It’s designed to function by itself, with none human intervention. An extra profit is that there are fewer parts in comparison with glass vials, so that you don’t need to cope with stoppers, crimp tops, and different closures. There are not any equal cleansing steps to those glass vials have to undergo. There are additionally no equal therapy steps to those glass vials have to undergo, akin to depyrogenation. Uncooked resin is used; it goes straight into the BFS machine and is molded straight. So, there are fewer parts, fewer steps within the precise manufacturing course of, and there’s far much less human interplay.
PharmTech: Are you able to clarify chilly temperature BFS and its advantages in comparison with common BFS?
Wong (Woodstock Sterile Options): Chilly temperature BFS requires implementing a mixture of strategies all collectively in a single manufacturing course of to assist management the quantity of warmth that’s imparted onto a drug product. Throughout the typical BFS course of, there’s naturally fairly a bit of warmth, as a result of uncooked resin is being melted to make bottles. The bottles themselves additionally must be heat all through the method in order that the containers may be sealed shut within the remaining step. There’s latent warmth, however Woodstock Sterile Options has discovered methods to manage that warmth in order that biomolecules can survive with no affect via the manufacturing course of. With a chilly BFS course of, there are further drug merchandise which you can bundle, because you should not have to fret about medicine which might be thermally delicate. Many biomolecules are warmth delicate, and there are numerous proteins that may denature or degrade with warmth, so historically, the biopharma business has stayed away from BFS and caught with glass—a tried-and-true choice. Having this assortment of producing steps expands what is feasible for drug merchandise in blow-fill-seal.
Implementing BFS expertise
PharmTech: What are some key issues when implementing BFS expertise?
Wong (Woodstock Sterile Options): One essential consideration is knowing the drug product’s compatibility/interactions with plastic. Earlier than choosing BFS, there must be an understanding of how the product interacts with plastic—if there are issues about adsorption or absorption, for instance. Moreover, plastic containers are permeable in a means that cup will not be, and it’s essential to grasp if that may have an effect on the product all through its shelf life. That being mentioned, there are methods to counter permeation, whether or not it’s water vapor transferring out or oxygen transferring in, with the intention to keep the standard of the product inside. Lastly, though BFS can be utilized to fill liquids which might be extremely viscous, if the product is extra ointment-like, then it will likely be troublesome to fill utilizing BFS. That makes it tougher to push via the piping and different components of the system, however the expertise can deal with a variety of viscosities.
PharmTech: What are the drawbacks of utilizing BFS expertise, if any?
Wong (Woodstock Sterile Options): The permeability talked about earlier is one problem, as are the fabric interactions I famous. Additionally, there are challenges with warmth and thermally delicate merchandise, however these may be addressed utilizing chilly BFS.
PharmTech: What are the regulatory and compliance issues when utilizing BFS, if any?
Wong (Woodstock Sterile Options): FDA considers BFS as a complicated aseptic manufacturing approach, recognizing its capability to provide sterile drug merchandise reliably whereas additionally making certain a excessive degree of high quality for sufferers. The business is held to the identical requirements, as all drug packaging applied sciences are, to make sure product security and high quality.
S. Bondre, et al., ARPB 3 (4) 494–499 (2013).
In regards to the writer
Alivia Leon is an assistant editor for Pharmaceutical Know-how, Pharmaceutical Know-how Europe, and BioPharm Worldwide.
Vol. 46, No. 9
Pages: 37, 51
When referring to this text, please cite it as A. Leon, “Bettering Sterility Utilizing Blow-Fill-Seal Know-how,” Pharmaceutical Know-how 46 (9) 37, 51 (2022).