FDA hopes pharmaceutical manufacturers will address packaging- and labeling- related errors before they even occur. Sound impossible? Not if you consider the agency’s interest in human factors engineering and its design control requirements for medical devices.
FDA has expressed its concerns related to pharmaceutical packaging in two recent draft guidances, “Safety Considerations for Product Design to Minimize Medication Errors,” released in December 2012, and “Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors,” released in April 2013.
Irene Chan, PharmD, with FDA’s Division of Medication Errors Prevention and Analysis (DMEPA), spoke about the two drafts and mentioned an upcoming additional document at RxAdherence April 8 in Florham Park, NJ. As its name suggests, DMEPA works with pharmaceutical companies in an effort to prevent medication errors, beginning in 1999 as a consultative arm of the agency.
“DMEPA determines whether there is enough evidence to release a design in terms of usability,” explained Chan. FDA’s first draft guidance urges companies “as early as possible in the design process to think about the environment of use and of patients,” she said. “Is there more than one patient group? What about caregivers? What critical tasks must they perform? What are the environmental factors? How are drugs stored and obtained in the environment? What other products are used?”
Manufacturers should “evaluate designs using proactive tests using risk assessments,” she explained. Such early testing can help companies “identify error-prone features and eliminate them from designs.” Testing can include FMEA, which systematically evaluates a proposed product design, Chan said. It gives designers the chance “to step back and see the whole picture to see the largest concerns and their serious outcome,” she explained. And then there’s simulated-use testing, which can “help determine whether users can safely and correctly perform critical tasks,” she said.
CDER recommends human factors studies . . . to address issues before they occur,” she said. For such testing to be effective (as well as cost effective), designers should employ them as early on as possible. “Don’t rely on controlled clinical studies to evaluate product performance,” warned Chan.
FDA’s second guidance on container and carton labeling refers users to these analytical methods discussed in the first guidance while giving specific direction on ideal approaches to package and label design. For instance, the “Principal Display Panel” should feature the following as most prominent: proprietary drug name, established drug name, and product strength. USP also requires expiration dating.
“Crowded labels make it difficult to find what is most important,” Chan said. “Exemptions are not available when label space is available.”
FDA would also like “easy-to-read font” to be used, such as a 12-point san serif, when space is available. There must be “adequate legibility,” Chan said. Tall-man labeling, in which dissimilar letters are placed in caps to avoid mix-ups between two look-alike names, as well as differentiating between different product strengths, can also be helpful.
The agency “discourages the use of logos, bars, stripes, lines, symbols, watermarks, and graphics,” she added. “Don’t superimpose text over images or logos, and images of tablets should not compete in size or prominence with the three most prominent features mentioned.”
Color coding should be “avoided in most instances,” added Chan. “It could increase error when relied upon as a shortcut.”
Speaking about “unit-dose blister packaging,” Chan said the agency is “all for innovation and ways to improve compliance.” However, listing “days of the week” on blister cards “could lead to delays in starting therapy,” and numbering doses could “be confused with product strength.” And “dosage” should match dosing.”
FDA is working on a third guidance on proprietary names, and the agency expects a draft to be published sometime in the summer of 2014. Chan urged the audience to “ask for a meeting with the agency on design,” and to do so early on during development.
“The earlier you can come to talk to the agency to bounce ideas off us, the better it would be. Our goal is better outcomes for patients.”
Wrapping Up Support
Packaging and labeling suppliers welcome FDA’s proposed changes to packaging and labeling design.
“The FDA draft guidance on ‘Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors’ is an important step in the right direction,” says Gene Dul, president of Schreiner MediPharm U.S. “Considering how crucial safe and efficient processes are in healthcare practice to avoid potential risk for the patient, labels can play an important role in supporting healthcare personnel in safe drug administration. The draft guidance lists recommendations on how good label design can mitigate the risk of medication errors and underlines how important it is to consider the end users and their environment of use when developing and designing a drug product’s label. Actually, this is an approach every label supplier should have in mind when developing a customized solution for a pharmaceutical manufacturer’s product and its specific application.”
George Toso, prepress manager, Lean Six Sigma Green Belt, Clondalkin Pharma & Healthcare, says that “the new labeling format provides an easier format for the consumer to find important information. The structured approach that the FDA has mandated provides a standard for displaying information that is useful to the consumer, regardless of the manufacturer or drug.” Suppliers are actively working toward solutions. “Every new item or revision we receive from our customers can have an impact on the safety of patients,” says Toso. “We continually assist customers in designing packaging that ensures that all information is captured in a way that helps guide proper use.”
But pharma companies most likely will need to make room for such labeling changes. “FDA’s recommendations mainly refer to graphic design to make products more likely to be correctly identified, however, in all cases what they suggest will require more space,” says Marc Oosterlinck, director of new business development for CCL Label HealthCare. “The Expanded Content Label has space for far more information than the conventional label type, and our ECL and two-ply and three-ply constructions would help pharmaceutical label designers comply with these FDA recommendations.” The two- and three-ply labels have up to five surfaces for additional information: the top ply, the back of the top ply, the front and back of the middle ply, and the base, he explains. “Between the layers of this label is a repositionable adhesive with a thin strip of a permanent second adhesive to form the hinge. There is a non-adhesive tab that facilitates opening, revealing the additional information on the two inside panels,” he adds.
Toso says many of Clondalkin’s customers “are converting to our Extended-Content Label designs as label copy requirements expand.” Dul says that mistakes with reconstitution could also be addressed with labeling. “According to the FDA, reconstitution processes harbor a high risk of medication errors. When refilling injection solutions, for example, from a vial or ampoule into an unlabeled disposable syringe, this might lead to administration of the wrong drug or wrong strength. Therefore, the FDA recommends transferable or peel-off labels for injectable medications. By equipping the primary container with a label that includes an integrated peel-off part, the peel-off section is instantly available at the point of product preparation and can be easily and reliably attached to the unmarked syringe. Also, it cannot be accidentally discarded as in the case of auxiliary labels provided with the carton.”
To meet FDA’s recommendations, Dul suggests Schreiner MediPharm’s Pharma-Comb SW solution, a member of the Pharma-Comb product family. “Pharma-Comb SW is a single-layered peel-off label, which is suited for labeling small containers for single-dose applications. The label is wrapped around the vial or ampoule and provides sufficient space for all critical information, as well as for the inscription of variable data and printing of barcodes. The peel-off part contains the product name, bar code, an area for post-printing of variable data, as well as space for manual inscription of dose, date and administrator’s signature. Thus, all crucial information is directly available at the disposable syringe after reconstitution. The peel-off part can be applied to the syringe like a flag without covering the graduation lines. The product details are easy to read and scanning of the code is simple. For greater ease of use when wearing gloves, the detachable part slightly lifts, so it can be easily peeled off when the label is opened.”