To minimize the operator intervention required for cleaning and changeover, the machine's product pathway is generally steam-sterilized
in place in an automated process. In the fill zone, a laminar flow of positive-pressure sterile filtered air maintains International
Organization for Standardization (ISO) 5 (Class 100) conditions. "The window of opportunity to have any type of contamination
is very small," says Tim Kram, general manager at Rommelag USA (Evergreen, CO), a builder of BFS equipment (Bottelpack BFS
machines). In addition, carefully designed ductwork and airflow manage the particulates generated when the parison is cut
off.
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Highly versatile, BFS is compatible with many products, container sizes, and packaging formats, including unit-dose containers.
Virtually any viscous or suspension fluid can be accommodated, and liquid-handling systems can be configured to blend multi-ingredient
formulations.
BFS container options include vials, ampuls, bottles, plungerless syringes, and custom containers. Designs often are squeezable
and may be equipped with bellows to aid dispensing. Containers also can incorporate a number of built-in features such as
twist-off opening; dropper, stopper, piston, or cannula inserts; cutting-ring or self-piercing threaded closures; and Euro-Caps
for infusion bottles.
Changeover time varies. If a BFS machine is used to make a family of containers, changing mold inserts to switch between 2-,
3- or 5-mL sizes, for example, can take two to four hours. Full mold changes will take longer, probably about eight hours.
However, many pharmaceutical packaging lines minimize changeover downtime by dedicating machines to a single style and size
of container or by running a narrow size range so only mold inserts need to be changed.
BFS container sizes extend from 0.1 to 10 L, although no single machine is capable of running this entire range. "BFS is especially
well suited for small unit doses," says Kram, noting that it's impossible to buy a glass vial in a size smaller than 3 mL,
and that prefilled syringes cost more than BFS containers.
Output speeds depend on the machine model, number of mold cavities, container size, container weight, type of resin, and product
characteristics. Smaller containers can be produced faster (i.e., at a maximum rate of 500/ min), but the run rate for the
largest sizes is not likely to exceed 30/min.
A typical automated line integrates the BFS machine with inspection equipment and, sometimes, cap welding, labeling, pouching–overwrapping,
cartoning, or case packing. But inspection and secondary packaging operations are often performed off-line or even manually.
The servo-controlled, high-speed Bottelpack 4010M BFS machine eliminates hydraulic components and features a continuously
rotating chain of molds. (IMAGE IS COURTESY OF ROMMELAG)
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In general, every container is inspected. A visual inspection checks for particulates, while a high-voltage or vacuum leak
test verifies container integrity. Inspection systems also may check container shape and lot number or date coding. Like that
of other sterile packaging processes, the validation of aseptic BFS systems includes media fills and microbial challenges.
Costs
Initial capital costs and a well-established base of glass packaging lines remain hurdles to the adoption of BFS technology.
Installing a BFS line at a brand-new site can easily cost $10 million. Although much of this investment relates to infrastructure
and space for related operations such as compounding, resin handling, and quarantine, the price tag for a BFS machine is substantial,
typically in the $1.5- to $2-million range. Prices for high-speed systems approach $4 million. Other costs relate to "the
quality of staffing required for qualification, validation, and continued support," says Gary L. Hanley, business director
and chief executive officer of Asept Pak (Malone, NY), a packager of sterile water, saline, technical products, and medical
devices and owner of four BFS machines.
However, when one compares the overall cost of aseptic BFS with that of packaging in traditional sterile glass ampuls, vials,
or bottles, BFS cuts expenses by about two-thirds because it eliminates the purchasing and storage step for containers and
components, as well as handling related to cleaning, sterilizing, filling, and sealing. "If container forming, filling, and
sealing can be done in one machine, you're light years ahead in labor and cost alone," explains Reed.
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