Blow-Fill-Seal: Guiding Quality
FDA’s aseptic processing guidance adds blow-fill-seal operations to the mix, giving users some direction
If you run blow-fill-seal (BFS) operations, chances are you welcomed FDA’s latest guidance on aseptic processing. Issued in September 2004, “Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice” spells out FDA’s expectations of industry in terms of contamination control and quality assurance in BFS operations, among other things. The agency’s recommendations are included in Appendix 2.
Sidebar 1: Dey LP Chooses High-Speed Unit-Dose Pouching
Before issuing this document, FDA offered little or no guidance on BFS.
Chuck Reed, sales manager, Americas, for Weiler Engineering (Elgin, IL), a provider of BFS machinery, says that FDA incorporated many of industry’s suggestions into the appendix. Weiler provided comments, Reed says, and FDA listened. As a result, “industry now has a clear definition of blow-fill-seal and understands how it fits into the aseptic processing world.”
In the guidance, FDA identifies three BFS steps that present the “greatest potential for exposure to particle contamination and/or surrounding air.” These include the steps “in which the parison is cut, moved under the blow-fill mandrel, and the mandrel is removed, just prior to sealing.”
FDA says that “BFS machinery and its surrounding barriers should be designed to prevent the potential for extraneous contamination.” The environment surrounding the machinery should meet or exceed Class 100,000, and air in the critical area should meet Class 100 microbiological standards during operations.
To help users follow these suggestions, Reed says that Weiler’s equipment features advanced components such as isolation systems as well as environmental monitoring and control systems. “Local protection of the environment” is key, he says.
Users who haven’t “looked at new technology may need to upgrade their equipment,” says Reed. To address environmental control issues, Weiler is “working to get away from the use of hydraulics above the base of the machine and toward the use of electronics, such as servo-driven filling systems,” he says.
Training may also be an issue for some users, says Reed. According to FDA, “only personnel who have been qualified and appropriately gowned should enter the classified environment surrounding the BFS machinery.” Section V of the guidance should be consulted when training, qualifying, and monitoring personnel, writes the agency. “Some companies may need to retrain their employees,” says Reed.
Rommelag’s latest machine is a new generation of the company’s bottelpack aseptic blow/fill/seal machine, model 324. “All movements are electrically controlled by way of servomotors,” explains Anke Henke. “No hydraulic system is installed, but could be used as an alternative, if so requested.” She says that the new machine features exact and precise positioning and repeatability of all drives; speed, acceleration, and changes are all adjustable at the control panel. Less maintenance is required, and there is easier control of complex movement sequences and less start-up time after design change.
Henke adds that Rommelag also offers its bottelpack machine for coextrusion, for handling five layers (PE or PP, binder, barrier material, binder, and PE or PP).
Sidebar 2: Blow-Fill-Seal Blow-Out
Using insertion systems inside BFS packaging environments is likely to increase. Isolation systems for component insertion is particularly important, says Reed. Weiler builds systems for tip-and-cap insertion for controlled drop delivery of ophthalmic drug products as well as for multiple-entry rubber stopper insertion. These systems are “in vogue” right now at FDA, since they “get people out of the room,” says Reed.
Gary Hanley, CEO of start-up Asept Pak (Malone, NY), believes that BFS holds the future for liquid unit dosing. He believes that FDA will begin to encourage unit-dose packages in the future, given its sterile presentation. The firm has purchased three Rommelag machines and is seeking another for large-volume production. “I believe our facility may be able to serve the smaller market in terms of unit numbers per run. We have made a particular effort to obtain very versatile machines in this vein,” he says. Asept Pack plans to be fully operational in June 2006, initially packaging sterile eyewash, saline rinse, and saline as well as water for injection.
There is also demand for nonsterile blow-fill-seal packaging. John Snedden, president of Unicep Packaging (Sandpoint, ID), describes a growing market for OTC cold products, homeopathic drugs, and nutritional supplements for retail sale in unit-dose BFS packages, all nonsterile. To meet such demand, the company has just scheduled installation of two Weiler 624 BFS machines in the next three to six months. “Unlike most BFS machines, these are nonsterile machines,” he explains. “Unicep wants to provide a lower-cost alternative for customers who want high volume BFS but do not need sterility. Simply put, sterile filling costs more than nonsterile filling, so this will give nonsterile customers a price alternative.” Both machines will run polypropylene and low-, medium-, and high-density polyethylene.
CRUCIAL SET UP
FDA clearly sees the benefits offered by BFS operations. “Advantages of BFS processing are known to include rapid container closure processing and minimized aseptic interventions,” the agency writes in its guidance.
But maintaining the integrity and consistency of these systems is crucial for product and package quality. FDA therefore encourages users to pay close attention to “to setup, troubleshooting of equipment, and related aseptic personnel procedures. Equipment sterilization, media fills, polymer extrusion/sterilization, product-plastic compatibility, forming and sealing integrity, and unit weight variation are among the key issues.”