Compliance prompting packaging: 'The light bulbs are coming on'

It’s been said that seeing is believing.

Such is the case with pharmaceutical companies, who for many years held the belief, but lacked the scientific evidence, concerning the impact of using compliance prompting packaging. Now following the release of two significant studies coupled with patient-cliff and healthcare-reform initiatives, demand for compliance prompting formats in both starter-pack style physician samples and commercial packaging are gaining wider acceptance as a means for generating better health outcomes, experts say.

“There have been studies in the news in the last year that have shown unit dose packaging (UDP) does contribute to increased patient compliance,” says Frederick Lutz, a regional sales manager at Constantia Flexibles (Vienna; US HQ in Blythewood, SC), a flexible packaging supplier. “Additional studies are ongoing and promising.”

Last year, Walmart (Bentonville, AR) adopted two types of calendarized blister packs for its pharma products as part of its commitment to help customers “live better,” according to published reports. This included MeadWestvaco’s (MWV; Richmond, VA) new Shellpak Renew, which features a tear-resistant, recyclable outer carton, an easy-slide blister, an integrated calendar for patients to track their medications, and billboard space for patient education. The package is available at more than 5,500 major retail pharmacies nationwide, including Walmart.

MWV says Shellpak Renew was developed based on feedback from pharmacists and patients. “Medications prepackaged in Shellpak Renew make dispensing medications quicker and easier so that our pharmacists can spend more time counseling our patients, including providing instructions on how to take their medications,” says Sandy Kinsey, VP, pharmacy merchandising at Walmart. “In addition, the calendared packaging helps reinforce to our customers how to take their medications safely and effectively for the best outcome.”

Walmart’s increased adoption of unit dose compliance prompting formats served as a major endorsement of UDP and reportedly helped create an uptake in the use of these packaging solutions. “Certainly, Walmart’s adoption of this style of packaging has fueled this momentum, and you are seeing that now with other major chain pharmacies,” observes Justin Schroeder, a senior director at AndersonBrecon (Rockford, IL), a contract packager. “The light bulbs are coming on.”

The proof is in the pudding, as recently published research reaffirms what UDP suppliers have been preaching to the pharma community for years: Increasing patients’ adherence to their medications through the use of compliance prompting packaging can positively impact patient health outcomes. Case in point: a first-of-its kind study published in the May 2011 issue of peer-reviewed journal Clinical Therapeutics conducted by Venebio and funded by MWV found that when used alone, MWV’s Shellpak calendar blister packaging demonstrated a statistically significant impact over vials, improving adherence and persistence for long-term daily medications. The study reportedly involved more than three million Walmart pharmacy patients.

Additional studies revealed similar results, proof positive that packaging pills in blister packs are far more likely to enable patients to take their medications. In a 2012 study, published in the journal Patient Preference and Adherence, researchers from Novartis Pharmaceuticals (Basel, Switzerland) and consulting firm Xcenda (Charlotte, NC) examined pharmacy claims from more than 9,000 patients taking hypertension drug Diovan HCT over the course of one year.

Approximately half the patients received their medication in MWV’s Shellpak, a calendared blister pack, says Hung Le, senior director, innovation, at MWV Healthcare; the other patients received their medication in a traditional pill vial. The study found patients using Shellpak refilled their prescriptions five days sooner and stayed on their medication 22 days longer.

While such new developments are promising, several hurdles stand in the way of greater adoption of compliance packaging for pharma products. One of the biggest relates to cost, as production, shipping and storage expenses may be viewed as unnecessary. And there remains resistance in the pharmacy community, observers say, which is reluctant to change traditional practices.

While additional evidence needs to be gathered to ascertain whether it is more cost-effective to utilize blister packs in drug-regiment adherence, some industry members believe this is negligible when you consider the annual cost of nonadherence. This figure in the US alone is estimated at nearly $300 billion, or roughly 13% of total healthcare expenditures per year. A 2012 study by Capgemini and HealthPrize Technologies, a medication adherence technology developer, saw a $188-billion gap between current US pharma revenue and the revenue level assuming full compliance. Drug makers can reap financial benefits from greater refill adherence. “We foresee a trend that pharmaceutical companies who utilize adherence packaging solutions during clinical trials will see the benefit in continuing to use similar packaging for the commercialized drug,” MWV’s Le says. “It’s important that adherence is encouraged from the very first time a patient interacts with a medication and its packaging—whether it’s in a clinical trial, a physician sample or a commercialized drug.”

The core function of compliance-prompting packaging is to ensure a patient takes their medication as prescribed by their healthcare provider. This includes dosing, frequency, timing and conditions. But approximately one-third to one-half of all patients do not adhere to their prescribed treatment plan and almost one-fifth of new prescriptions go unfilled, according to industry studies.

Poor medication adherence can lead to worsening of disease, serious and avoidable health risks, increased hospitalizations and even death. An estimated 10—25% of hospital and nursing home admissions are a direct result of medication non-adherence and 23% of long-term elder care admissions in the US are a consequence of failed adherence.

“Medication packaging has been scientifically proven to have a positive impact on patient adherence, both when used alone or in combination with other adherence interventions,” Le says.

UDP innovation

UDP is widely used for sample packages as an important brand-communication experience and considered a near-necessity for drugs with different titrations over the course of a therapy, notably birth-control pills. But a major objective for suppliers is expanding UDP into more conventional multiday-dose regimens. Walmart and Kroger (Cincinnati, OH) are among the pharmacies where blister packs with calendar markings for pills are already used for certain medications.

“Unit-dose packaging is more diverse and has the capability to protect the product, not only from environmental factors, but also serve or solve compliance issues, brand identity issues, counterfeiting problems and communication issues,” says Ajith Nair, SVP of research and development, Bilcare Research (New Castle, DE), a packaging solutions provider. While such benefits position UDP as an attractive alternative to other packaging solutions, such as bottles, it is harder to navigate the safety requirements of the Consumer Products Safety Commission (CPSC), which pushes manufacturers to provide both “child-resistant” and “senior-friendly” packaging, and has testing protocols for both. This is a necessity for many over-the-counter cough/cold/allergy products.

“Functionality is always an issue, as care must be taken into design to maximize the child-resistant aspect of the package while still ensuring that adults—and especially seniors—can access the medication without great difficulty,” Constantia Flexibles’ Lutz says. “It is always a fine line to walk, but design elements can be engineered into the blister—such as greater land area, good access to peel area, clean perfs, etc., to meet both objectives.”

Achieving the appropriate child resistance level by dexterity and overcoming cognitive barriers to accessing the actual blister card are said to be among the biggest benefits of new compliance packaging solutions. There has been a great deal of work done in recent times to improve functionality in compliance prompting packaging, particularly related to consumer friendly features. “The industry has long ago accepted that packages will need to have F1 Child Resistance (CR) ratings,” says Walter Berghahn, executive director at the Healthcare Compliance Packaging Council (HCPC; Bon Air, VA). “The features required to make packages F1 frequently increase the difficulty for adults to access as well as the intended audience of children under 48 months.”

In the last few years, there has been increasing interest in new ways to package drugs in F1 CR/Senior Friendly formats in a blister. Companies such as MWV, Constantia Flexibles, AndersonBrecon, Keystone and many others spend a great deal of time designing, testing and redesigning features to increase the senior friendliness of the package without compromising the F1 CR rating.

For instance, Constantia Flexibles developed its “Easy-Piesy” CR blister material which utilizes film instead of paper, Lutz says, allowing for a cleaner peel, and keeps paper fibers out of the equation. Keystone Folding Box (Newark, NJ), a producer of paperboard packaging solutions, has introduced a child-resistant F1 senior-friendly compliance package called Ecoslide-RX made from 100% recyclable material. Ecoslide-RX enters the market as a solution for Rx products, physician samples and clinical trial materials that meet and exceed sustainability objectives adopted by an increasing number of organizations, according to the company.

On the Rx side of the business, suppliers report utilizing higher barrier films, as more products require better protection, both in thermoformed and cold-formed “foil-foil” structures. This would also include films with integrated desiccant and/or oxygen scavengers due to the moisture or oxygen sensitivity of some newly developed molecules. The use of desiccants and oxygen scavengers are driven by the stability needs of the drug.

This form of “active” packaging—which interacts, in some fashion, with the tablet—is reportedly gaining traction in the pharma community. “This is certainly being explored, along with ways to better interact with users/patients,” says Victor Dixon, president and COO, Rondo-Pak (Eagleville, PA), a designer and producer of cGMP compliant pharmaceutical folding cartons. “Active packaging and interactive technologies, such as digital watermarking, can combine to provide a host of benefits to both the brand owner and the consumer/patient.”

There are suppliers who support several commercial programs using desiccated materials or integrated oxygen scavengers within the packaging. For example, AndersonBrecon reports having commercialized blister designs using PET films as well as high-barrier applications with such materials. AndersonBrecon is planning to launch the first commercial application of its IntuiPac CR/SF design as well as for an NDA product, pending FDA approval of the drug. “The IntuiPac has an intuitive push-thru access to the patient and requires no special patient instruction to access the product,” Schroeder explains.

Active packaging can also mean intelligent packaging with embedded electronics, providing prompting for the consumer or links to other “smart” devices. The latest developments in this area are being driven largely in response to the complexity of products produced. “As drugs become more complex, they are often more susceptible to environmental impact—moisture, oxygen, and light—and can require special packaging features to protect them and their efficacy until the patient uses them,” HCPC’s Berghahn points out. “But this discussion should not be limited to complex features embedded in materials or housed in the package.”

Smart packaging is considered a reliable and proven method for electronically capturing and analyzing patient adherence data. MWV offers several smart packaging solutions, including its Medication Event Monitoring family of products: MEMSCap, Cerepak and Helping Hand. “These products are currently used primarily as part of our adherence monitoring and analysis solutions for clinical trials,” Le says, “but are also available for commercial usage.”

At Bilcare Research, significant development in the smart packaging realm is underway, Nair says. “Possibilities include communicating or indicating the state of drug products packed, or the exposure conditions they have undergone—even indicating exposure time, temperature, humidity level, etc.”

Emphasis on visual aids

Further developments in UDP packaging center on providing a visual cue to act as a reminder in two different fashions. The first is a reminder if the patient took the medicine as prescribed and the second is an indication of doses remaining so the patient knows when the prescription needs refilling. “UDP brings enhanced patient communication through visuals and designs, and lead directly to improved compliance,” Nair says.

To that end, Cardinal Health (Dublin, OH) introduced a multi-dose packaging solution last October, to help its retail and long term care pharmacy customers make it easier for their patients to adhere to their medication regimens. Cardinal Health is now the exclusive reseller of multi-dose medication packaging kits, blister packs, labels and other supplies from Dispill-USA. The cold-sealed, patented, multi-dose packaging system is marketed as a simple, safe and convenient way for patients to ensure they are taking the right medication, at the right dose, and at the right time.