OR WAIT null SECS
Heightened concern over adherence and product stability may win over more pharma clients
Fig. 1 AstraZeneca’s Seroquel (top), the 2014 HCPC winner; Lilly’s Strattera (middle); Novartis’ Exforge (bottom)
Pharma manufacturers (and their contract packaging providers) who are considering compliance (unit-dose) packaging have three trends to take advantage of:
Unit-dose packaging (mostly blister cards, but including foil pouches and, in some contexts, single-use prefilled syringes) has been a source of struggle for its proponents for years; while many European markets are accustomed to unit-dose packaging for many oral solids, and were ahead of the US in adopting prefilled syringes, the US market is dominated by the ubiquitous amber bottles with 30-day supplies dispensed at the local pharmacy. While pharmacists sometimes complain of the chore of filling our prescriptions by manually counting out pills, they are also protective of that step as part of their reimbursed services. Manufacturers, for their part, have long identified filled bottles as the lowest-cost option for delivering either 30-day supplies of an oral solid, or bulk containers whose pills are then counted out at the local pharmacy.
“In the US, less than 20% of oral solids are in unit-dose packaging; outside the US, the proportion is reversed,” notes John Zripko, president of Bilcare Research (Delaware City, DE), which provides a full range of films and cards for unit-dose packaging. He sees growth in this type of packaging being propelled by two drivers—an overall goal of higher quality standards in packaging (an element of which is stability issues); and the greater degree of branding that the combination of cartons and blister cards affords. The company has been a provider to WalMart, which private-labels a number of chronic-care drugs that are sold through its pharmacies; these packages include calendar features to aid in patient compliance, and are labeled with WalMart’s logo.
The range of compliance features in unit-dose packaging have been exemplified by the annual winners of the Compliance Package of the Year, conducted by the Healthcare Compliance Packaging Council (Bon Air, VA); this year’s winners were announced at its RxAdherence meeting (March 31, Florham Park, NJ). The 2014 winner is a blister-carded 14-day sample kit from AstraZeneca, for its Seroquel XR (extended release quetiapine), an “atypical antipsychotic” for treatment of a variety of mental health conditions. First runner-up is Eli Lilly’s Strattera (atomoxetine, for ADHD) physician’s sample pack, and second runner-up is the Exforge HCT blister package. Novartis’ Exforge HCT (amlodipine, valstartan, hydrochlorothiazide) is indicated for high blood-pressure treatment and is taken daily.
All three products make use of package designs from MeadWestvaco (Richmond, VA); specifically the Dosepak design for Strattera and the ShellPak Renew for Exforge. Packaging Coordinators Inc. (Philadelphia, PA) is the contract packager for Strattera and Exforge.
Both Seroquel and Strattera kits include carefully laid-out processes for titrating appropriate dosages for patients beginning therapy. For Seroquel, noted John Grinnell, managing director, Secondary & Adherence, MWV Healthcare, in a statement, “The initiation of this medication regimen is complex, with daily doses and numbers of pills adjusting throughout the titration process. Both patients and providers needed a hands-on tool to help guide medication initiation.”
A number of patient-support features also stand out among these award winners. The Strattera package includes patient education facts regarding ADHD as well as information directing patients to a supporting website to establish an online goal-setting progress resource, as well as information for prescription savings for the patient. The Seroquel package has a multi-panel insert (instead of the usual loose leaflet) for convenient storage and reading.
Rondo’s SafePack carton both packages and protects fragile biopharmaceuticals. Credit: Rondo-Pak
Innovative packaging designs are a hallmark of the packaging suppliers and contract packaging organizations serving the pharma industry, which thus has a multitude of options to choose from. At Rondo-Pak (Norristown, PA), there is a focus on the cartons needed for containing biotech products (for example, prefilled syringes or glass vials); the company is introducing SafePack, an all-paperboard container that has shock- and vibration-resistant features to protect the drug, as well as patient convenience in opening the container and gaining access to the syringe. “Patients using therapies for, as an example, rheumatoid arthritis need ease-of-use features for access to the drug,” notes Victor Dixon, president of Rondo-Pak.
SafePack has a double-walled construction and auto-actuating cushion flaps on its top and bottom that protect against severe impact and provide higher crush resistance than standard cartons (Fig. 2). It was also designed to accommodate on both manual and automated packaging lines. Other containers make use of thermoformed plastic trays and/or foam cushioning; this design replaces all of that with 100% recyclable paperboard.
The branding capabilities of paperboard cartons are also being featured in another Rondo-Pak offering, the Multi-Media Carton, which incorporates a thin, lightweight video display screen. The device is intended for starter kits, clinical trial packaging or sales demonstrations; the advantages of providing video-based instruction for patient compliance are compelling. In an era where drug regimens can cost patients and their insurers thousands of dollars monthly, Rondo-Pak is betting that the cost of the package can be justified by a better patient experience.
Fig. 3. PCI performs both clinical packaging (top) and commercial packaging (bottom); patient instructions can accompany packaging in both instances. Credit: PCI
The clinical element
Mention of clinical packaging brings up the trend in overlapping industry needs between clinical packaging, starter kits and compliance packaging for commercial use. Research organizations running clinical trials have a constant worry that patients are keeping on therapy during the course of the trial; at the same time, patients who have been prescribed a product (especially for chronic care) need better resources to address adherence, as evidenced by the industry’s average of 50% compliance after initial fill.
“Clinical packaging designs come out of close consultation with the study manager,” notes Justin Schroeder, director of marketing at Packaging Coordinators, Inc. (PCI). That company, in addition to its substantial capacity for commercial contract packaging, has expanded its clinical packaging services, partly through the acquisition of Biotec Services International (Bridgend, UK) last year.
Schroeder notes that multinational trials have a pressing need for providing the instructional materials in multiple languages; by thoughtful design of the package carton, instructional pamphlets and the like, these needs can be accommodated economically. The parallel with starter kits is apparent; similar packaging designs can be used in that case as well (Fig. 3). PCI performed the design and manufacturer of the Eli Lilly Strattera package that was the first runner-up in the 2015 HCPC competition.
Fig. 4. Rondo is marketing a Multi-Media Carton with an integral video screen. Credit: Rondo-Pak
HCPC, together with Bilcare Research (as coordinator) and Legacy Pharmaceutical Packaging, LLC (St. Louis, MO), Klockner Pentaplast of America (Gordonsville, VA), Constantia Flexibles (Wall, NJ) and Morristown, NJ-based Honeywell (as materials suppliers) published a study last fall, “Prescription Packaging In-Use Stability,” to demonstrate an acknowledged concern in pharma distribution: the stability of products after they have been received by patients. The premise, simply put, is that the barrier properties of unit-dose packaging offer better protection of shelf life than the conventional package of pills in a bottle that are doled out (usually) once daily from the patient’s medicine cabinet.
Concern over the effects of light and humidity are well known; there are vendors of desiccant packs that are often packaged with pill bottles to protect the drug. The study concluded that “Degradation results indicate that simvastatin, lisinopril and metformin when dispensed in vials, HDPE (high-density polyethylene) bottles or PVC (polyvinyl chloride), undergo changes through daily exposure to typical home environments. Whether these changes can affect these drugs’ specific efficacy or their absorption rates needs further investigation.”
Bilcare’s Zripko notes that the issue is bigger than what occurs in the typical medicine cabinet in the typical US home. “As pharma markets become more international, dealing with more climate conditions, there will be a greater need to deal with these stability concerns,” he says. And while manufacturers are required to conduct stability studies as part of the drug-approval process, Bilcare has developed a service called Optima, to simulate stability characteristics based on the design and composition of the unit-dose packaging being used. The service is gaining greater acceptance among pharma drug developers, he says.