Medical Device Link.

Originally Published PMPN November 2001

SUPPLEMENT

Unit-dose tubes, trays, pouches, bottles, and blisters keep product sterile and at the ready.

Daphne Allen, Editor

Unit-of-use packaging, also called unit-dose packaging, is widely considered to be effective at helping consumers adhere to drug regimens. "Studies have shown that unit-of-use packaging with compliance-prompting features offers better persistency in simple and complicated drug regimens, which improves efficacy," says Renard Jackson, executive vice president of sales and marketing for PCI Services, a Cardinal Health Co. (Philadelphia).

Adds Angela Roggenhofer, healthcare marketing manager for Hueck Foils LLC (Wall, NJ): "It is quite obvious that unit-of-dose packs such as blisters considerably improve compliance, with the result of increased efficacy of the drug, leading to higher probability of its being represcribed or rebought."

Physicians and pharmacists appear to agree. According to a survey of 3000 physicians and pharmacists by Honeywell (Morristown, NJ), the maker of Aclar, 82% of responding physicians and 87% of responding pharmacists would like to see drugs packaged in compliance-enhancing designs, explains Honeywell's healthcare market specialist Bill Sharpless.

Improved drug compliance is certainly an important benefit. However, a number of other benefits of the unit-of-use package make it an appealing option. Cleanliness. Convenience. Ease of use. Safety. Accuracy. "The benefit of unit-of-use packaging is enhanced compliance, sterility, and cleanliness. It is also the most portable and discreet way to package," says Greg Shaw, director, business development–contract packaging for Margo, an Alcan Packaging company (Montreal). "The disadvantage is higher packaging costs. However, this balances out due to higher sales from a more-compliant use of the medication."

NO MESS

When Kevin Thomas of Omnii Oral Pharmaceuticals (West Palm Beach, FL) set out to market his firm's new fluoride varnish, he knew he couldn't introduce it in packaging similar to that of products already on the market. Competing products are packaged in 10-ml tubes. "When dental professionals use these tubes, they often forget to recap them, and the product, which has the consistency of tree sap, dispensed on its own and got very messy," he explains.

Plastic unit-of-use tubes from James Alexander can be customized with unique applicator tips. Shown here are a swab tip and a dropper tip.

Instead, Thomas wanted to employ some sort of unit-of-use package, like some of his firm's other dental products were packaged in. A consultant pointed out Lollipack single-use packages displayed by Centrix Inc. (Shelton, CT) at a dental products show, and Thomas was intrigued.

The Flexible Packaging Association gave Glenroy a Top Packaging Award in 1998 for its plastic and foil pouch for Cool Mint Listerine Antiseptic Mouthwash.

After having test packages filled and sent to pediatric dentists for product trials, Thomas was convinced that the Lollipack eliminated the mess of multiple-use packaging. Consisting of a polypropylene tray divided into eight wells and covered with a scored foil/polypropylene lid, the Lollipack package allows users—in this case dental professionals—to break away each well of product as needed. The design is ideal for "materials that normally come in a jar or a tube that would be opened and reclosed," explains Bill Dragan of Centrix. "It eliminates mess at the point of use."

ENSURING INTEGRITY

Neatness isn't the only virtue of a unit-of-use package. One of its biggest benefits is its ability to keep its contents intact and away from contamination. "Unit-of-use packaging offers sepsis control," says Thomas. Adds Dragan: "Our biggest competitor would be bulk packages like jars, squeeze tubes, and bulk syringes, which promote contamination of the unused materials."

Glass ampules and snap-top vials from James Alexander can be provided in borosilicate (USP-type I) glass.

Steve Dilts, director of sales and marketing for Unicep (Sandpoint, ID), a provider of unit-dose packaging, says that "a growing number of dentists have come to expect unit-dose packaging for almost every product they use. In fact, many dentists consider their use of unit-dosed products as a way to build patient confidence in the cleanliness and safety of their dental operatory. Patients are made aware that each product to be used in the procedure is being opened just for them."

Gary Bobko, vice president of sales and marketing–packaging film for Glenroy Inc. (Menomonee Falls, WI), agrees that unit-of-use packaging keeps products cleaner. "A critical concern of our medical and pharmaceutical customers is package integrity. By individually packaging their product, their customer is assured of cleanliness," he explains. Glenroy offers a variety of laminations that can be formed into pouches, die-cut into a variety of shapes, used as hangers, and included with other packaging materials such as blisters and folding cartons.

When unit-of-use packaging is made with barrier materials, the combination provides a packaging environment that remains stable until product use. Glenroy's Bobko and Jim Gilstrap, a product manager at Rexam Medical Packaging (Mundelein, IL), both point out that demand for high-barrier materials is increasing, particularly at the unit-of-use level. "High barrier is being driven by more moisture-sensitive products, often due to the new emerging, fast-dissolving technologies," explains Gilstrap. For example, Rexam provides barrier pouches for transdermal- delivery patches and other moisture-sensitive products.

"The use of high-barrier films for pharmaceutical unit-dose packaging not only offers protection from moisture ingress, it ensures that drugs will be protected under the harshest conditions that may be encountered in the distribution channel," adds Kent Sides, pharmaceutical business manager for Klöckner Pentaplast of America (Gordonsville, VA). "This is why high-barrier films are more frequently used to ensure maximum speed to market for new healthcare products."

Howard Thau, president of Sonic Packaging (Westwood, NJ), explains that many of the unit-of-use pouch materials that his firm is "presently using offer a great barrier to properly contain the product, offering extended stability and compatibility."

Chosen for Blue Copper 5 was James Alexander's one-piece molded plastic unit that remains intact until activated by a one-handed squeeze.

For example, Wyeth-Ayerst chose a high-barrier pouch for its Rapamune product, a prescription immunosuppressant liquid. According to Bob Hargesheimer, vice president and general manager of West Pharmaceutical Services Inc. (Lionville, PA), which worked with Wyeth-Ayerst, the pouch was chosen instead of a bottle primarily to maintain stability.

Unit-of-use glass ampules have also extended the shelf life of streptococcus test kits, explains Francesca Fazzolari, president of James Alexander (Blairstown, NJ). Previously used packages had limited shelf life, but isolating the liquid in a glass ampule protected the product from breaking down and from contamination, she says. Now, more than a million glass ampules are used every year in these kits.

Unicep's Dilts has seen an interest in preserving active ingredients. "Many actives are sensitive to oxygen, light, or moisture contamination that occurs with an opened jar or tube. Unit-dose packaging can eliminate this problem."

Unit-of-use packaging is especially useful for medical devices that need to remain sterile until deployment in a surgical suite, adds Hueck's Roggenhofer. For such devices, in 2001 Hueck introduced a gamma radiation–sterilizable lidstock that can seal to PETG, which is commonly thermoformed for medical device trays.

Medical procedure kits also allow ease of use, with all procedural components packaged within a single sterilized kit, notes Richard Ryder, business manager of medical device films, for Klöckner Pentaplast.

Bobko says that some unique laminations have been used to package syringes. For instance, BD Pharmaceutical Systems' UniJect, a prefilled injection system containing a liquid vaccine for use in developing countries, needed a multilaminate pouch with a foil layer. "The foil helps minimize moisture loss," explains Peter Heyman, manager of customer process development. "It also provided a light barrier."

Rexam's Gilstrap also finds unit-of-use packaging to be appropriate for sterile medical products. "The main purpose of unit packaging has always been to maintain sterility for medical devices. In bulk packaging, once the package is opened to remove a product, the protection has been compromised."

SAFETY NET

Thomas's choice of the Lollipack for his firm's fluoride varnish did much more than create a cleaner, easier-to-use package. It also limited the amount of product applied. This is especially important in Thomas's case: The fluoride varnish would be used by dental professionals on children. "It is a high-strength product with known toxicity levels. We had to package it in a way that would promote safety," he explains.

Single-dose packages from Glenroy were selected for (clockwise from top left) Cholestech Lipid Profile, Triaminic Softchews, Cyclofemina syringes, Perform pain-relieving gel, Maalox antacid tablets, and Checkmate blood glucose tests.

Thomas and his team chose to package the product in two different volumes—a 0.25-ml product for primary dentition and a 0.40-ml product for mixed dentition consisting of both primary dentition and permanent teeth. Each package has its own applicator, a Benda brush that dentists use much like a paint brush.

For added safety, these brushes are color coded: A yellow brush is used for the 0.25-ml product that Thomas says indicates "Caution—fluoride product," and a red brush is used for the 0.40-ml product to signal "Warning—Don't use on children with primary dentition."

Such safety features help ensure that the product is used correctly, regardless of the user. "In some cases, fluoride varnishes are used in WIC [women, infant, and children] clinics and are often put in the hands of nontechnical personnel," Thomas says. "The Lollipack offers added protection by providing the right tools for application, contamination control, and the right dosing."

Dragan adds that Centrix offers the Lollipack with different applicators. Centrix itself markets the Lollipack to dentists filled with topical anesthetic with a cotton swab as the applicator. The product is used in dental offices and is also given to patients for home treatment of postoperative pain. "The swab mimics the dentist's current technique of dipping a swab in a jar, sometimes multiple times with the same swab, and then placing it in the patient's mouth and holding it on the area to be numbed for a number of minutes. By providing a unit-of-use pack with its own disposable applicator, a dentist can double-dip to his or her heart's content," Dragan explains. In addition, Centrix is also in the process of putting together an OEM OTC topical anesthetic in the Lollipack for consumer use. "In that case, the integral applicator gives the patient something to suck on, similar to a lollipop, while the 20% benzocaine gel takes effect," he explains.

Controlling dosing through unit-dose packaging use takes the guesswork out of drug administration. "You don't leave dose determination up to the patient," explains West's Hargesheimer. "There is little risk of under- or overdosing. It leads to better outcomes."

Glenroy's Bobko echoes the same verdict for medical devices: With unit-of-use packaging, "the serious concern of duplicate use of a device or instrument in error is dramatically reduced."

Thau finds that a premeasured, prepackaged dose makes drug administration easier: "Our custom liquid blisters are being used by marketers of ingestible products that offer the consumer a premeasured dose in an easy-to-use primary package. In one case, we designed a blister in the shape of a spoon for a children's cough remedy. Our customer wanted to differentiate themselves from the other products being offered and at the same time give the consumer an easy-to-use package."

Packaged in Lollipack, Centrix's liquid dentin desensitizer D/Sense is supplied with its own Benda Brush applicator.

And some unit-of-use packaging can increase the precision of drug delivery. Says Thau: "Tubes typically are used to dispense a unit dose of a liquid or cream and are good for dispensing one drop at a time in a specific area or region."

Unit-of-use blisters can also be used for liquids. Earlier this year, Margo introduced its line of unit-of-use liquid blisters designed to complement its line of injection-molded unit-of-use tubes, says Margo's Shaw. Formed like blisters for solid doses, the liquid blisters are "filled on the fly" in a continuous motion using a proprietary filling system installed on a high-speed thermoformer. "The blisters are more cost-effective than the unit-of-use tubes, and they may be suitable when the delivery feature of the tube is not needed," he explains.

BREAKING AWAY

An added benefit is that unit-of-use packages tend to stand out from their multiple-dose competitors. Not only are these packages distinctive in size and shape, but they can also carry dedicated text and graphics to aid in use and recognition. Michael Castaldo, vice president of technical operations and development for Reed-Lane Inc. (Wayne, NJ), points out that unit-of-use packettes give firms ample copy area.

To make full use of that space, packaging professionals often rely on printing. "A major trend that we see in the medical and pharmaceutical markets is the demand for high-quality printing," says Glenroy's Bobko. His firm relies on an eight-color flexographic operation, which he says "offers excellent print quality with fine type and small copy and allows for shorter runs and quicker changeovers in an economical fashion." This year Glenroy won six awards for its printing.

Sonic Packaging's sister company, Xtreme Printing & Packaging, also prioritizes high-quality graphics, using flexography, lithography, and gravure printing for multiple-color graphics, says Sonic's Thau.

Packaging individual doses does cost more, though. Glenroy's Bobko admits that "the cost to individually package a unit-of-use product is more expensive than multiple-dose packaging." However, West's Hargesheimer thinks that because consumers are increasingly looking for more-convenient products, "the market is willing to pay more for that convenience." Adds Castaldo, "The convenience, stability, and security of unit-of-use packaging far outweigh any disadvantages."

And, as consumers adhere to their regimens better by administering the right amount of product, Bobko says that "the liability exposure to the product manufacturer is minimized."

Photo courtesy of James Alexander Corp.

Copyright ©2001 Pharmaceutical & Medical Packaging News