BFS know-how can assist keep sterility in the course of the biologics manufacturing course of.
Blow-fill-seal (BFS) know-how presents a number of benefits over different aseptic strategies, corresponding to flexibility in packaging design, the power to make sure a excessive stage of sterility assurance, and sustaining low prices (1). As well as, the usage of BFS know-how limits human involvement, which additional improves the extent of sterility assurance by eradicating a major contamination issue from the method totally. The know-how enhances the power to kind the container and closure in the course of the packaging course of, which permits for a extra customized design of the container. BFS know-how can thus be used to fulfill particular wants and enhance container ease-of-use (1). To be able to be taught extra on the logistics, advantages, and potential drawbacks of BFS know-how, Pharmaceutical Expertise spoke with Waiken Wong, PhD, supervisor of growth engineering at Woodstock Sterile Options, an Illinois-based supplier of sterile growth and industrial options.
Advantages of BFS know-how
PharmTech: Are you able to please clarify what BFS packaging know-how is and the way it applies to bio/pharmaceutical manufacturing?
Wong (Woodstock Sterile Options): Blow-fill-seal packaging know-how is a technique the place the container is fashioned, full of 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 medication, together with biopharmaceuticals. Sterility is important for biologics and lots of different medication as a result of it prevents microbial contaminants in merchandise.
PharmTech: What advantages does BFS packaging know-how provide, in comparison with conventional glass vial manufacturing?
Wong (Woodstock Sterile Options): There may be far much less human intervention when BFS packaging [is employed], and people are the largest explanation for contamination. Contamination can have a adverse impression on microbial sterility. As a result of the BFS course of occurs fully inside the cupboard of the machine, there’s little likelihood 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. A further profit is that there are fewer parts in comparison with glass vials, so that you don’t need to take care of 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, corresponding to depyrogenation. Uncooked resin is used; it goes instantly into the BFS machine and is molded instantly. 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. Through 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 might be sealed shut within the remaining step. There may be latent warmth, however Woodstock Sterile Options has discovered methods to manage that warmth in order that biomolecules can survive with no impression by way of the manufacturing course of. With a chilly BFS course of, there are further drug merchandise you can package deal, because you would not have to fret about medication which can be thermally delicate. Many biomolecules are warmth delicate, and there are numerous proteins that may denature or degrade with warmth, so historically, the biopharma trade 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 know-how
PharmTech: What are some key issues when implementing BFS know-how?
Wong (Woodstock Sterile Options): One necessary 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 manner that tumbler will not be, and it’s important to know if that may have an effect on the product all through its shelf life. That being stated, there are methods to counter permeation, whether or not it’s water vapor transferring out or oxygen transferring in, as a way to keep the standard of the product inside. Lastly, though BFS can be utilized to fill liquids which can be extremely viscous, if the product is extra ointment-like, then it is going to be tough to fill utilizing BFS. That makes it more durable to push by way of the piping and different components of the system, however the know-how can deal with a variety of viscosities.
PharmTech: What are the drawbacks of utilizing BFS know-how, 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 might 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 sophisticated aseptic manufacturing method, recognizing its means to supply sterile drug merchandise reliably whereas additionally making certain a excessive stage of high quality for sufferers. The trade 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).
Concerning the writer
Alivia Leon is an assistant editor for Pharmaceutical Expertise, Pharmaceutical Expertise Europe, and BioPharm Worldwide.
Vol. 46, No. 9
Pages: 37, 51
When referring to this text, please cite it as A. Leon, “Enhancing Sterility Utilizing Blow-Fill-Seal Expertise,” Pharmaceutical Expertise 46 (9) 37, 51 (2022).