Catalent Pharma Solutions continues to develop its in-house processes and product portfolio for ADVASEPT technology, a glass-free, polypropylene vial produced by blow-fill-seal (BFS) operations that is suitable for a range of biopharmaceuticals and pharmaceuticals, including injectables. The company has completed several studies demonstrating its suitability as an alternative to glass packaging and continues to invest in enhancements.
Catalent’s BFS operation in Woodstock, IL, employs equipment from Weiler Engineering. The facility was formerly Automatic Liquid Packaging, which Cardinal had acquired in 1999. (Catalent divested from Cardinal as a private company in 2007).
“BFS has already been well adopted for sterile inhalation and ophthalmic drug products,” notes Bill Hartzel, director, strategic execution, advanced delivery technologies, for Catalent Pharma Solutions. He suggests that the technology should also be considered as an option for packaging injectable drugs, given some of the recent manufacturing challenges with traditionally glass-packaged injectable drugs.
“There have been quality challenges in the manufacturing of injectable drugs, which have resulted in a number of product recalls. These market actions have put a strain on supply and have even led to drug shortages,” says Hartzel. “FDA and industry organizations point out that the majority of the injectable drug shortages have been caused by quality and manufacturing issues such as the presence of particulates and microbial contamination.”
As an alternative, BFS containers are formed, filled, and sealed in seconds, within a class-A environment. “With the BFS processes, the container formation and filling operations are contained within the machine, eliminating the need for human intervention and never breaching the sterile boundary,” he says. “Additionally, our BFS processes are well studied and characterized to understand the critical control parameters such as the continuous monitoring for viable and nonviable air.”
The BFS technology also “eliminates glass management issues, such as cleaning, depyrogenation, and handling,” he adds.
Given polypropylene’s (PP) “inert nature, it offers an excellent chemical stability and eliminates glass interaction concerns,” Hartzel says. “PP has a significant amount of product contact history.” In addition, PP “is a robust and thermally stable polymer, so it can withstand the higher temperatures of an autoclave terminal sterilization process if needed.”
Hartzel adds that using the BFS technology offers “primary container design freedom when compared with glass, which is just tubular with size-change flexibility. With BFS, packages can be flat, feature multiple ports, or even serve as a delivery device all the while providing sterility assurance and an efficient manufacturing process.”
There is also “a lot of flexibility” in what components can be inserted into the BFS container during the process. “Pre-assembled and pre-irradiated product components such as stoppers can be fed to the BFS machinery via an isolator and hopper, which are then handled through automatic insertion and then sealed to form an integral container,” says Hartzel.
In addition to understanding the BFS process, Catalent has worked to provide a more comprehensive data package on the container closure. They have generated two-year real-time stability data on the packaging of WFI and saline in the BFS vial. They have performed a full extraction study on the primary and secondary components of the BFS vial.
Additionally, Catalent is conducting a long-term stability study with a model monoclonal antibody in the BFS polypropylene vials compared to glass. “After 9-months, the biologics case study data shows that packaging products in ADVASEPT is comparable to packaging them in glass,” says Hartzel. “After 16 different tests, we have found no statistically significant difference.”
In terms of concerns about the heat associated with BFS processes, Hartzel says the drug is exposed to such heat for a short time. “Heat is evacuated and the mold temperature returns to equilibrium in about two seconds,” he says.
Last year Catalent presented the technology at the Manufacturing Technology Seminar Series hosted by FDA’s Office of Compliance and Biologics Quality. According to Catalent, FDA had specifically invited the company to present its ADVASEPT technology as well as Zydis, its fast-dissolving technology in a freeze-dried oral dosage form that disperses almost instantly in the mouth, requiring no water.
Catalent’s profiles can help streamline some of the work drug manufacturers would need to perform, Hartzel believes. The company offers regulatory and analytical services to help drug manufacturers transition from existing packaging to BFS vials.
Catalent has also conducted a concept study with nurses that demonstrated that over 90% of those interviewed “saw value in glass-free container closures over traditional glass vials,” the company reports.
Catalent’s current BFS capacity is flexible, and Hartzel says much of that flexibility comes from Catalent’s established knowledge of BFS machinery and processes. “Our knowledge of the machinery is foundational to our capability,” he says. “Our goal is to have the right size equipment to match the drug product need at the right phase of the development lifecycle,” he says. “We can handle smaller pilot runs for development, which is what we are seeing with more expensive products these days to minimize product loss and have the processing expertise to efficiently scale these up to commercial production.”
In addition to adding to its stability data, Catalent’s future plans include expanding its product portfolio to support custom sizes and more insertions.
For more information, visit www.catalent.com.