Expanding Options for Blow-Fill-Seal Packaging

Biologics are driving some process modifications.

The growing biologics- and protein-based drugs market continues to be a bright spot in the pharmaceutical industry. Pharmaceutical Business Review recently reported that “by 2010, annual sales of biologics will have increased by $26 billion, compared to a $13 billion increase for small molecules.”

Blow-fill-seal packaging (BFS) is an option for many of these emerging products. Some of the more heat-sensitive biologics, in particular, may be protected by the aseptic handling inherent to BFS processing.

“We have demonstrated recent success in research and development and with an actual product the stability of a heat-sensitive product,” says Chuck Reed, director of sales and marketing for Weiler Engineering (Elgin, IL). “We are also working with materials maintained cryogenically, where the products would be kept at sub-zero temperatures, using a proprietary resin.”
Reed sees increased awareness of BFS processing and FDA’s recognition of the aseptic method. FDA issued “Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice,” in September 2004.

“Advantages of BFS processing are known to include rapid container closure processing and minimized aseptic interventions,” the guidance reads. “However, only a properly functioning process can realize these advantages. We recommend affording special attention 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 to address in validation and qualification studies.”

Ever since the guidance’s release, Reed has seen increased inquiries. He credits such interest to the growth in biotech, but also to growth in the traditional niches for respiratory and ophthalmic products. “Some of these established products are coming off patent, and the generics makers are looking at BFS packaging, even if the brand was in another packaging
format,” he says.

FDA notes that BFS “is often used for filling and packaging ophthalmics, respiratory care products, and, less frequently, injectables.”

So if you are marketing an injectable biological drug, the data you gather during validation and qualification studies “should ensure that BFS containers are sterile and, if used for parenteral drugs, nonpyrogenic,” FDA advised in 2004. “This can generally be achieved by validating that time temperature conditions of the extrusion process are effective against endotoxin or spore challenges in the polymeric material.”

New BFS requests are looking at novel delivery methods. While the primary focus is on the unit-dose formats BFS offers, potential BFS users are asking about new delivery systems for both single and multiple doses.

Multidose BFS packaging for vaccines, for instance, is being considered because the package could get vaccines into the hands of practitioners and serve the greatest number of patients, Reed says. The novel delivery systems include Weiler’s designs for multientry inserts.

By adding a rubber or silicone stopper to the blow molded container, Weiler creates a package similar to traditional multiple-entry vials. Weiler has provided this technology to a contract packaging firm for use in its own technology.

In addition, Weiler offers technology for welding caps onto BFS packages. A fully automated cap-welding system is available, as is a semiautomatic, manually loaded system. Recent upgrades include making “the systems easier to maintain and more flexible to accommodate competing systems’ geometries,” Reed says.

To fully accommodate the biologics market, however, requires working with smaller batch sizes than those typically seen for pharmaceuticals. It is a challenge, as BFS is often adopted for its economy of scale. “Vaccines are a definite growth market for BFS, given the volumes in the vaccine market,” says Reed. “To accommodate the smaller batches, though, we are looking at potential process modifications.”

Reed adds that he is also working with PDA to start a “noncommerical, grassroots effort to promote the
science of BFS and its potential for parenterals.”

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