Tapping the Potential of Blow-Fill-Seal
The trend toward unit-dose packaging is adding momentum to adoption of blow-fill-seal (BFS) technology, as applications expand in areas including parenterals, oral liquid formulations, and diagnostic testing.
BFS containers are being investigated for supporting new drug delivery systems, and for new uses in the home, where unit-dose formats support precise, convenient administration.
|Blow-fill-seal packages courtesy rommelag USA Inc. (Evergreen, CO). Photography by Hector Torres.|
BFS unit-dose ampoules have taken hold in OTCs, another promising growth segment where BFS’s production efficiency and cost-effective sterility assurance are advantageous.
McNeil Consumer Healthcare’s Childrens’ Zyrtec and Childrens’ Benadryl feature Perfect Measure single-dose packaging, where each container holds a 0.5-ml dose. Robitussin-To-Go from Wyeth Consumer Healthcare features two and ten-count unit-dose packs of BFS ampoules.
In this packaging, the user twists off the top, places an integrated spoon device in the mouth, and squeezes to channel the liquid to a hole at the tip.
“We are seeing a broad spectrum of BFS applications, with the fastest growth in unit-dose applications. The advent of personalized medicine and the drive to more simplified dosage formats including the need for increased patient compliance with multiple drug regimens is creating opportunities for BFS,” says Chuck Reed, director of sales and marketing, Weiler Engineering Inc. (Elgin, Il).
BFS unit-dose containers are established as preferred packaging for respiratory drugs. Companies are favoring unit-dose formats in ophthalmic, inhalation drugs, oral liquids, and vaccines, to derive benefits in consumer use.
“Delivering the drug in the proper concentration and dose size is important to many drugs. Ophthalmic and oral dose liquid companies are moving products into unit-of-use dose from existing multi-dose preparations. Unit-of-use formats also allow for product preservative removal which reduces adverse reactions to the product,” says Tim Kram, general manager, rommelag USA Inc. (Evergreen, CO).
Generics have been quick to embrace the technology, in packaging that follows the brands.
“The cost pressures in the generics markets are strong drivers for this extremely cost effective technology. Most BFS products are produced at less than one-third the cost of a comparable conventional aseptically packaged product,” says Reed.
“We are seeing particularly strong growth in the BRIC nations (Brazil, Russia, India, and China), where the generic market for injectable products has been a growth area. There is tremendous interest in BFS as a sustainable technology due to the relatively low carbon footprint, and the use of easily recyclable material in the process,” Reed adds.
Several large global pharmaceutical companies are using rommelag’s BFS bottelpack machines for high-speed, large-volume IV solution packaging that replaces traditional IV dosage forms like bags, glasses, and other pre-manufactured bottles, says Kram. “Worldwide, the only major countries not utilizing BFS bottles for IV solutions are the United States and Canada,” he adds.
As BFS is adopted for packaging biologics, new resins and processes for material and process compatibility are being evaluated.
“We view BFS as both a high-quality and efficient means of packaging unit-dose and multiple-dose sterile pharmaceuticals,” says Michael Riley, VP, business development Catalent Pharma Solutions (Woodstock, IL).
“The BFS market is most highly developed in the respiratory and ophthalmic segments. We have had good experience and success bringing biological products in BFS to market (such as) with unit-dose vials of respiratory drugs used with nebulizers. We also see the potential for expanded use of BFS in the injectable area,” Riley says.
“You have to do a feasibility study in each case to determine the compatibility with the packaging material, and if products will require special handling. With biologics, we have used traditional BFS materials (LDPE and HDPE), as well as polypropylene,” Riley adds.
With biologics, the temperature the product will see in the filling process has to be managed. “The plastic resin is extruded at very high temperatures, which promotes the molding and also sterility. Though the bottle rapidly cools in the mold, it still contains some heat when the product is filled. We have had good success in limiting the heat exposure,” Riley says.
Weiler-designed ASEP-TECH Blow/Fill/Seal systems have successfully produced millions of vials of heat-sensitive products, including biologics, says Reed. “We are continually evaluating new resins for specific applications. We can assist customers in their verification of the compatibility of the drug with the container. Each drug must be individually characterized specifically with the proposed packaging for extractables, leachables, and vapor transmission” Reed says.
Reed says BFS is promising for packaging pandemic virus vaccines, though this market has not yet been open to the technology.
“There is a great deal of interest in both multi-dose and unit dose formulations for these types of drugs. BFS supports the need for pandemic virus vaccines to be produced in multiple locations rapidly for simple delivery to a large population. The fact that BFS systems can be placed in relatively limited spaces and are self-contained with minimal operator intervention makes them ideally suited for placement in emerging markets,” Reed says.
In enlarging the applications for its BFS bottelpack technology, rommelag has developed Co-Extrusion technology for multi-layer containers addressing contact layer compatibility and barrier protection. Co-Extrusion heads that handle up to seven layers can be fitted to most rommelag BFS bottelpack machines, Kram says.
Holopack Verpackungstechnik, a Stuttgart-based contract packager, is installing a rommelag multi-purpose CoEx BFS bottelpack machine with the co-extrusion technology for manufacturing unit-dose and larger volume bottles for packaging oxygen-sensitive solutions.
In the Holopack application, five servo-driven extruders create a five-layer parison of LDPE, EVOH and LDPE, with binding layers of a modified-LDPE.
“Other plastic and barrier material combinations are possible (dictated by) products’ needs. Holopack has been developing products for several years on a CoEx BFS bottlepack test machine. With the installation of the new production machine, we expect to see an acceleration of new contract-manufactured products (using this technology) coming to market,” Kram says.
NEW DELIVERY SYSTEMS
Companies are exploring the use of BFS closed aseptic containers in single and multi-dose with novel delivery systems. Weiler is working with device suppliers to produce BFS packaging in cartridge formulation for home application of specific drugs, Reed says.
Rommelag also reports device projects in progress. “The device may use one container per use or be set up with a BFS cartridge for multiple use prior to refilling—the device opens the sealed container in a controlled method,” Kram says.
For injectable applications, BFS containers with twist-off cap and luer connection replicate the rubber-stoppered glass vial. “Rubber or silicon stopper inserts provide a multi-dose option to the traditional glass ampoule, while offering improved safety in handling—there is no glass breakage,” says Reed.
A single Weiler unit often incorporates the stopper insert design, along with the capacity for placement of integrated tip and cap inserts for permitting tight drop control and delivery from multi-dose ophthalmic product containers, Reed says.
Weiler’s insertion technology can insert custom injection molded delivery devices, such as dual-chamber designs separating a liquid fill and an inserted lyophilized pellet.
“ASEP-TECH BFS systems have the added advantage that a non-insertion design such as a standard spike top or twist off top container can be produced on the same machine with a simple change tooling by turning off the insertion feature,” Reed says. 0