Despite the challenges, more and more companies are designing successful compliance packaging.
Ben Van Houten
Compliance--or more accurately, noncompliance--is a bigger problem than ever for healthcare manufacturers. Just look at the staggering statistics: An estimated $100 billion in lost sales and more than 300 deaths a day, according to the Healthcare Compliance Packaging Council (HCPC; Falls Church, VA), all as a result of patients failing to take their medications in the proper dosage or at the right time. In addition, the American Health Care Association (Washington, D.C.) reports that 10% of hospitalized patients are admitted because of incorrect medication usage, with 23% in nursing homes for the same reason. Even more startling: a 2002 study published in Pharmacotherapy revealed that up to 28% of all emergency-department visits were related to misuse of prescription drugs, with 70% of these having been preventable. A 2003 study by the World Health Organization (Geneva), titled Adherence to Long-Term Therapies: Evidence for Action, essentially sounds the call to action. It concludes: "Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the world population than any improvement in medical treatment."
And while use of unit-dose, blister, and other forms of compliance packaging is certainly at an all-time high, the challenges remain big, too. Whether it's the higher manufacturing costs, the challenge of designing packaging that meets strict child-resistant/senior-friendly (CR-SF) regulations, or simply the struggle to convince patients to be compliant, manufacturers and packagers have a Herculean task on their hands when it comes to producing effective compliance packaging.
"The biggest challenge to package design and process engineering is to deliver packages that are practically manufactured at high speed and low cost," says Joe Lally, director of sales at Howell Packaging (Elmira, NY). "Simply capturing a single blister inside a printed card, the most basic form of compliance packaging, is no real challenge. It is the additional custom requirements that add complexity."
Child resistance is chief among those requirements. Not only is it often complex and costly to manufacture a CR blister, but when senior-friendly requirements and compliance enhancement are factored in, it can get downright overwhelming.
"The requirements are tough to meet," says Glenn Groskopf, vice president of product development, Colbert Packaging Corp (Lake Foreset, Il). "I've been through the CR tests, and they're brutal. Kids are throwing packages around and pulling off caps."
The CR-SF Challenge
Despite the roadblocks, a growing number of companies are successfully meeting this challenge head-on, with designs that combine innovation with practicality. Nowhere is that more evident than in the winners of HCPC's 2003 compliance packaging awards. Procter & Gamble's Actonel 35-mg Dosepak, Merck's Emend packaging, and TAP Pharmaceuticals's Prevacid Napra PAC Combination Therapy Dosepack utilize CR features coupled with unique design elements.
The Actonel Dosepak, patented by MeadWestvaco (Mebane, NC), has passed CR protocol testing, achieving the highest rating of F1. (In this rating, access to one unit constitutes a failure.) Procter & Gamble (Cincinnati) adapted the Dosepak for Actonel, a once-per-week dose regimen to prevent and treat postmenopausal osteoporosis. It contains an extra flap on the top of the package to provide more space for instructions. A fifth and sixth panel combination produces a pocket containing the patient information leaflet.
Similarly, the Emend package was particularly noted by HCPC for its CR feature. The drug, which consists of a postchemotherapy regimen of three tablets dosed in two days, is packaged in a carton that employs tear-off pull-down strips designed to restrict child access. Ginny Chang, PhD, senior project engineer for Merck (Whitehouse Station, NJ), notes that the package's CR features are the most critical. "Kids are getting so much smarter," she says. "But I also had to create a CR feature that was accessible for seniors, too. You don't need a lot of strength to open the package, which makes it ideal for seniors."
Chang adds that when she began designing the Emend, the challenge was obvious. "How could one package do all this? What would be the easiest way to design it, with the least amount of parts?" she says. "We talked with manufacturers who didn't think it was achievable." Chang and her team worked close to three years to develop the final result, which seniors tested in malls throughout Toledo, OH. "It's difficult to balance the CR and SF features," she admits. She also wanted to make sure Merck's contract packager wouldn't struggle with production. "We made it as easy as we could for them, in that it's a one-step process: fold it and heat seal it," she says. "We wanted to make it as machinable as possible for them."
Another company, Caraustar Industries, worked with GlaxoSmithKline (GSK; Research Triangle Park, NC) on Lamictal, an antiepilepsy drug which took first place in HCPC's competition last year. Caraustar provided heat-sealed carding and final assembly of the package, which was originally designed with five weeks of dosing on four separate cards. However, the two companies redesigned the package to incorporate the same amount of dosing on a single card. The card folds down into one compact package.
Still, the difficulties associated with incorporating CR and SF features are numerous. "Achieving that delicate balance is a formidable challenge," admits Lally from Howell. "Add in the desire to have a cost-effective package that can be run at high speed, and the task is even greater." To that end, Howell has instituted a CR package development program. The program recently gained the company F1 certification for the howell.CR.III package. That package is capable of running at high production speeds and is an economical alternative to other CR packages on the market, according to Lally. "It also rates extraordinarily high in the senior-friendliness category," he says.
Compliance Still The Main Goal
While CR-SF--focused packaging is perhaps the biggest challenge, the main idea of compliance packaging--compliance itself--remains the ultimate goal. GSK had recent success designing the Trizivir Convenience Pack. This compliance package contains a 30-day supply of an antiretroviral drug for the treatment of HIV/AIDS.
Each dispensing carton contains 60 Trizivir tabs on a blister strip, giving patients a tear-off roll for twice-daily tablet dosing. The carton also provides patients with a dosage calendar to help them keep track of when they take their medication and alert them when a refill is needed. "With HIV, adherence is always a challenge. Patients take multiple drugs 2-3 times a day for the rest of their lives," says Mary Faye Dark, spokesperson for GSK. "We heard a lot from patients while we were designing the package, and they told us they don't want their lives to revolve around taking medication. But we still had to improve their ability to take the drug." Each tear-off strip is in a sealed blister and is easy for patients to drop in their pockets after using a dose, Dark explains. "In that sense, it makes compliance much easier and more convenient for them."
Cardinal Health (Philadelphia) is also committed to meeting the challenge of compliance packaging. The company's Slide-Pak was recently used in an Ohio State University study designed to test blood pressure medication compliance among the elderly. In that study, a control group using plastic prescription bottles was compared with a test group using the Slide-Pak. "The preliminary results show a significant increase in refill rates with the compliance package, as well as a significant decrease in blood pressure," says Renard Jackson, the company's executive vice president of sales and business development, packaging services.
Another company, DuPont Medical Packaging (Wilmington, DE), sees "significant unmet needs" in the compliance packaging market and plans to act accordingly within the next few years. "We've had success in medical packaging with our Tyvek protective material," says Mark Miller, DuPont director of marketing. "We want to augment that in a way that's suitable to pharmaceuticals and find a way to combine compliance with anticounterfeiting."
Collaborating With Physicians and Patients Pays Off
Some companies are also finding that the key to successful compliance packaging design is collaboration not only with pharmaceutical company clients, but also directly with physicians and patients themselves. "By working with your end-user first, and then designing your product around it, you'll have the greatest success," says Bob Carraher, group vice president of marketing for Taro Pharmaceuticals (Hawthorne, NY). Taro recently collaborated with Wal-Mart on the packaging of Warfarin, a medication for cardiac patients. More importantly, Taro collaborated with cardiologists on the design. "It's a lifelong therapy," he says. "As such, the cardiologists we spoke with called it the bane of their existence. Dose modifications were the norm rather than the exception, and their patients were switching dosing on a daily basis."
The cardiologists did a study for Taro that revealed 33% of patients were forgetting to take the medication. In response, Taro developed the SmartPak, which acts as a diary card that helps track dosing. The package's inside top flap/cover contains dosing instructions, with the days of the week presented horizontally on the inside bottom.
Taro test-marketed the package to patients in Connecticut and Texas, and the findings led directly to the final package design. "Our findings were that color-coding was a big plus, and that patients wanted a pocket with more information included. And the perforated, peel-off, push-through design was a great design in terms of CR-SF issues," he says. "Child-resistance was a big issue with this product because the medication was originally rat poison, in larger doses."
Warfarin, incidentally, costs 20% less than its name-brand counterpart, reports Carraher, which makes the SmarkPak less costly for Taro to produce.
In addition to working with a package's end-users, some companies are producing compliance products for the healthcare provider/dispensing side of the business. AmerisourceBergen (Valley Forge, PA) has just launched AutoMed technology, a new compliance packaging system for use in hospitals that dispenses patient medication in continuous strips of individual unit-dose or multidose packets. The flexible, easy-tear packets are tamperproof, can be labeled with a bar code, and contain solid oral medications in the correct dose, sequenced by administration time. The packets are divided into time of day and patient, so caregivers only pull doses needed for the immediate medication delivery, eliminating the need to stage the next dose or rotate medications. "This reduces the medication delivery time by up to 50% and improves a facility's efficiency," says Stephen Mitchell, the company's vice president.
At the pharmacy level, Mitchell says, a series of devices hold the medications in bulk form in a machine, which is used instead of vials. "For the dispenser, it eliminates the need for difficult-to-open blister packs, as well as any manual filling or labeling," he says. "It also has optional bar coding that allows bedside verification, which can help reduce errors associated with improper dosing or drug administration." In addition, the compliance system lets self-reliant patients take their medication with them when they're not in a hospital or care center.
New Technologies And The Future
Most are in agreement that the need for compliance packaging will continue to grow in the future. "As more sophisticated products are introduced, the need to strictly adhere to the dosing regime will be critical," says Lally of Howell Packaging. "The trend toward more compliance packaging will likely continue."
"Now is our time. I expect big growth in the next five years," adds Shawn Reilly, vice president of marketing for Anderson Packaging (Rockford, IL). "We have momentum. When these big companies realize that they'll sell more pharmaceuticals and make more profit with unit-dose, they'll jump on it more. Ed Hancock, president ofAmerican Health Packaging (Columbus, OH), is similarly optimistic. "It's accepted that this is a need, and there's a groundswell of interest out there. I think we're on the threshold of a revolution in compliance packaging."
If that is true, new technology will likely lead the way. "I'm seeing lots of interest in medications for diabetes and other diseases that require unit doses," says Hancock. Ned Simpson, of CSC Global Health Solutions (El Segundo, CA), likewise sees more future movement in the unit-dose direction. "New drug-delivery systems in particular will drive packaging toward unit-dose," he says. Cardinal's Renard Jackson concurs. "Numerous new technologies out there are moving away from tablets," he says. "Whether it's a patch or a fast-dissolving strip, you're talking about materials that lend themselves to unit-dose blisters."
The growth of tracking technologies might also lead to more compliance packaging. "RFID is going to generate an enormous amount of interest. How it can be used not only for security but also for compliance will help accelerate some new package designs that are in the works," suggests Peter Schmitt, president of Montesino Group (Wilmington, DE).
"Anti-counterfeiting has taken off as FDA has raised its profile," adds Scott Denley, marketing manager for Alcan Packaging (Shelbyville, KY). "We expect a big push for CR-SF compliance packaging when RFID becomes mandated."
Denley is also seeing an increase in carded blister production, which he sees as a growing trend. "We are also actively looking at new solutions with our current customers," he says.
Alcan's current product line includes peelable, peel-push, and tear-open packages. "Compliance packaging is an ongoing trend, and we will continue to focus on developing new products," he says.
Walter Berghahn, director of sales and marketing for Uhlmann Packaging Systems Inc. (Towaco, NJ), already sees more and more companies looking to bring wallets into the market. We are also seeing a huge increase in prefilled syringes."
However, some companies realize that compliance packaging still has limitations. "Blisters are popular, but the current standard of blister foils is limited," says Miller of DuPont. "There hasn't been much improvement in lidding and primary packaging in the last 20 years, and we see great potential there." Miller also sees a need for new package engineering ideas. "Sometimes it seems like packages are sophisticated but overengineered," he says.
There are still other reasons that compliance packaging hasn't exactly taken off. "The major companies haven't gotten on the bandwagon enough, even though the capacity in the marketplace is there," says Jackson. "It will take awhile until the major companies switch over to blister packaging. They've put together a capital structure to run millions of products in a bottle. For them to shift to blisters all of a sudden is a huge capital investment." He also notes the difficulty of complying with CR regulations. "Especially in the United States, that's tough," he says.
In Europe, however, it's a slightly different story. Only 20% of drug products are packaged in bottles there, as opposed to 80% in the United States. In addition, much of the equipment used in blister packaging comes from Germany. "There's a real push over there for compliance packaging," says Berghahn from Uhlmann. "Hopefully, we'll end up in the same place." There is also a newly formed European Healthcare Compliance Packaging Council. "Research is already increasing, says Tassilo Korab, director of business development, Teich AG (Vienna, Austria) and a board member of the European HCPC. "We have asked the Institute of Public Health at the University of Vienna to investigate the role of packaging in compliance."
Others have cited a fear that manufacturers will actually move away from blisters in response to ongoing FDA regulations, such as the recent bar code ruling. "That's a concern," says Ned Simpson of CSC. "We feel that FDA comes up short in requiring how the pills are sent to hospitals. We as an industry need to be providing hospitals with unit-dose products. How do we do that? It is a challenge."