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Besides the ongoing debate over serialization, drug labels are playing a greater role in anti-counterfeiting, preventing medication errors and improving patient adherence
Depending on your perspective, the pharmaceutical package label is either practically the last thing done on a packaging line, or the first thing a patient sees upon opening a carton. In either case, the label is a workhorse element of pharma packaging: providing basic identification of the drug bottle or carton contents (and, in the near future, unique identification of that package); critical usage instructions for the patient; anti-counterfeiting features (when used); and a linkage for patient education, medication adherence and other desirable tasks for therapy value. As such, the label is of concern not just to the packaging engineer concerned with its placement, but also to brand managers, compliance personnel, distribution workers, pharmacists and, in some cases, prescribing physicians. Hospital systems, now under the gun under healthcare reform to raise their level of patient outcomes, are seeking functional changes in all their suppliers to that aim, including the drugs they purchase. Getting the labeling right is a critical element of successful drug marketing and distribution.
Fig. 1. 3C Packaging’s newly installed flexo press handles multiple label substrates.Credit: 3C Packaging
“Pharmaceutical companies are looking for intelligent and cost-effective packaging solutions that meet diverse requirements and can be adapted to their specific needs,” observes Gene Dul, president, Schreiner MediPharm US (Blauvelt, NY). “Sophisticated labels can offer special functionalities while decreasing the environmental footprint and helping to ensure drug and patient safety.”
For years, FDA has emphasized the importance of providing accurate and readable information on drug labels to help educate and involve patients in their care. FDA recently took this initiative one step further by publishing a new guidance covering safety considerations for container labels and carton labeling design for Rx drugs and CDER-regulated biological products. The guidance provides a set of principles and recommendations for ensuring critical elements of a product’s container labels and carton labeling are designed to promote safe dispensing, administration, and use of the product.
“The guidance mentions design features that can distract the consumer or provider’s attention away from critical drug information, including product name, strength and dosage form,” notes Hung Le, senior director, innovation, MeadWestvaco Healthcare (MWV; Richmond, VA). “Specifically, FDA notes that adequate container label size is critical to enabling container label designs that help minimize medication errors.”
Patient adherence is a critical issue as industry studies reveal more than $300 billion in avoidable medical spending each year. “While patient attitudes play a significant role in adherence, pharmaceutical companies also share in this responsibility,” says Guillaume Kerboul, business consultant director, life sciences industry, Dassault Systemes (Lowell, MA). “Clear, concise directions on packaging are critical to bridging the adherence gap and directing patients to take medication regularly and call out expiration dates.”
Indeed, there is a movement among pharma companies to focus their packaging toward the end-user patient as part of an effort to sufficiently engage with them, industry members say. “What that means is rather than including as much information into packaging as possible, pharmaceutical companies are making critical information more accessible through a variety of techniques, including larger fonts and inserts,” Kerboul says. “Focusing on the end user helps pharmaceutical companies play a larger role in helping physicians treat patients.”
While patient adherence is a major consideration for drug label design, equally important is the effect it will have on deterring drug counterfeiting. In a report released earlier this year, the Institute of Medicine of the National Academies (IOM; Washington, D.C.) cited a drug industry study which revealed 1,623 counterfeiting incidents in 2011, with more than half involving fake packaging. “There is still much more conversation that needs to take place as an industry to obtain buy-in for the logistics of implementing a track and trace program that will function properly across the entire supply chain, including a discussion of data management at each stop along the way,” MWV’s Le says. “There should be discussion to ensure that the technology can be shared and transferred along the way as the drug moves from the manufacturer to the retailer.”
Some of these discussions are taking place on Capitol Hill. In early June, the US House of Representatives approved legislation to establish a track and trace system throughout the pharma supply chain. Supporters hope to reconcile the US Senate version, the Pharmaceutical Distribution Supply Chain Act, in time to submit to Pres. Obama in mid- to late summer, according to published reports.
Figs. 2, 3. Schreiner MediPharm’s Pharma-Tac Plus label (left) offers patient-administration advantages, and its Pharma-Comb Security labels (right) provide enhanced brand protection. Credit: Schreiner.
The House version of this bill, the Safeguarding America’s Pharmaceuticals Act of 2013, would establish a national standard of tracking requirements for drug makers, distributors, pharmacies and re-packagers based on changes in ownership. Products are to have serial numbers attached to the individual unit level, and to have some mechanisms in place to trace a drug lot through the distribution process. At the same time, the bill proposes to supplant multiple state laws with a uniform national standard—a desired goal for manufacturers and distributors, who would otherwise contend with a mishmash of varying state laws. However, there is widespread concern that the House bill undercuts the goals of the California e-pedigree law, set to go into force in 2015, which would enhance safety and eliminate redundant regulations, according to published reports.
The Senate bill, ratified by committee on May 22, would create a plan for transitioning from a lot-level to unit-level tracing system. During a seven-year period, the major areas of the supply chain would pass and maintain transaction data and history, as applicable, for individual pharma products. At the same time, FDA would create a guidance for industry participants on uniform standards to build an interoperable electronic tracing system.
Industry watchers say anti-counterfeiting solutions aimed directly at protecting the patient from fraudulent medication are commonly incorporated into the drug’s primary packaging label. The best security features meet the common sense criteria of “hard to duplicate, easy to authenticate.” Which raises the question of whether anti-counterfeiting features will be necessary if the serialization mandate is approved.
The answer, experts say, largely depends on the details of the mandate and how it will be enforced. In California, for example, the state drug pedigree law for prescription drugs will take effect in 2015, requiring product serialization and electronic pedigrees to accompany/validate drug distributions to prevent the entry of counterfeit medicine. “Many pharmaceutical manufacturers are not waiting for a serialization mandate,” says Kregg Albrecht, vice president, solutions engineering, Nosco (Waukegan, IL). “They have built security features into their printed packaging to protect their brand and patients alike.”
In the near future, some observers predict the combination of anti-counterfeiting efforts, regulatory aspects, and Obamacare will meld into a formidable force that will demand unique serialization. “The minimum mandatory requirement of the lot and batch of the medical device will make the implementation of unique serialization a logical step for corporate entities to limit liabilities and fight counterfeiting,” says Ken Koldan, new business development manager, FLEXcon (Spencer, MA).
Customized brand protection can be ensured by multi-level security systems. For example, 3C Packaging (Clayton, NC) says it develops a unique brand security strategy for each client to safeguard against medication errors. Schreiner MediPharm’s new Pharma-Comb Security label combines diverse overt and covert features. “Depending on the customer’s specific demands, the label could, for instance, be equipped with holograms, color-shifting security inks and guilloche patterns as well as covert features like voiding effects and LaserSecure, which uses special pigments that are only visible with the help of a reading device,” Dul explains. “Integrated, detachable label parts with additional security features make authentication checks possible, even after the label has been attached to the patient’s medical records.”
Pre-coding labels for serialization
Traditionally, packaging managers make a choice between generating label information on the packaging line (through various printing technologies that “convert” the label from a blank to a meaningful message, or to obtain pre-coded labels from a dedicated label converter. Label generation is now an example of “variable printing” whereby each label can be a unique identifier of the pharma package. Making the choice between dedicated label generation and outsourced generation is case-specific to each drug and how it is to be used, say industry experts.
There are many critical elements to developing a proper serialization program, experts say, starting with the physical printing of the code itself. Ideally, the code needs to be durable so it won’t scuff or abrade during its lifecycle and requires a reliable print method that does not add to packaging line down-time or bottlenecking. “One solution that should be considered is sourcing labels that are pre-printed with the serialized data,” Nosco’s Albrecht says, “thereby removing the headaches of variable printing in-line.”
Nosco offers pre-serialized labels produced digitally at a high resolution, protected by an abrasion and chemical resistant coating, and vision-inspected and verified. One challenge to consider with pre-serialized codes is the logistics associated with lot and expiry data. “Currently, some pharma companies have chosen to include this information within the variable barcode and others have not,” Albrecht points out. “If the pre-printed codes are to contain lot and expiry data, then a rapid cycle time model must be deployed, i.e. a digital print model.”
A major benefit of utilizing pre-coded labels is minimal capital equipment investment. The use of pre-printed labels does not require special printers or software. “The labels come ready to apply,” notes Russell Hill, technical innovations manager at 3C Packaging. “So there is no additional equipment to maintain and no need for validating new equipment.”
Some industry members believe on-demand printing may be the best way to go, as it allows changes to be made quickly and—if the label is designed as a template that draws its information from a database—without additional time for design or changes. “There will, of course, be the initial capital cost associated with new equipment,” Hill says. “But the overall residual label cost would be less, especially over an extended period of time.”
On the flip side, pre-coded labels can be expensive, as there are charges for performing services such as art work and die cut. And while pre-coded labels may save time at the packaging stage, there is concern about serializing labels that are not associated directly with product. “It brings into question how pre-coded labels will be managed and secured,” MWV’s Le says. “On the other hand, the use of pre-coded labels could provide drug packagers with an easier solution, as there would be less retrofitting required on their existing packaging equipment.”
Propagating data through the supply chain while maintaining record connectivity to the source data element is considered critical. Some companies will outsource that label data storage to a converter of label material and then use the pre-printed labels to increase line speed and throughput. “The downside is the loss of control that could stop the line and inventorying point a company is creating in the supply chain,” FLEXcon’s Koldan says. “There is no one-size-fits-all solution.”
While many packaging lines are outfitted with ink jet printers, lasers, or other marking equipment, efficiencies will be challenged with the added complexity of variable printing. If and when serialization becomes a mandate, packagers may have to think broadly, experts say. “How will hand packed items be coded?” Albrecht asks. “What about specialty items—is there enough space and tolerance for small containers? In this regard, pre-serialized labels can be a complementary solution and fill the voids that are incapable or not practical for in-line serialization.”
Fig. 4. MeadWestvaco’s Shellpak Renew container provides generous space for label and patient messaging. Credit: MWV
Safeguarding against medication errors
At the same time, labels can play an important role in ensuring patient safety and helping avoid medication errors. Problems with medication errors are well documented and estimated to cause 100,000 deaths annually in the United States, according to IOM. FDA has encouraged manufacturers to explore approaches to create larger container labels or unique packaging to accommodate all critical information on the immediate product container.
Schreiner MediPharm offers a multi-functional solution called Pharma-Tac Plus, which serves as a hanger label for infusion bottles with extended space for text information and additional detachable label parts. “Due to the multi-layered design, the label offers enough space for detailed product descriptions, while the integrated hanger allows the administering caregiver to quickly and easily hang the infusion bottle on a bedside rack,” Dul says. “And by utilizing the integrated, detachable label parts, the infusion can be documented in the patient’s medical records as well as the hospital’s files, ensuring reliable documentation and traceability of the administered infusion.”
Indeed, new technologies are changing the way pharmaceutical leaders think about patient adherence. For instance, next-generation diagnostics are already helping provide critical information in a wide variety of therapeutic areas—such as diabetes—and allow customized approaches for each patient. The development of the electronic pill bottle equipped with a wireless transmitter tracks compliance and reminds patients about the time of medication by flashing the bottle top and playing a tune. “There are companies working on packaging in 3-D to support this type of project,” Dassault Systems’ Kerboul says.
Meanwhile, barcode technology is becoming more sophisticated to help patients avoid medication errors. Observers say this is helping drive increased use of 2-D barcodes which contain additional data. For instance, the AIDC technologies being employed today with 2-D barcodes are able to implement systems inside their IT enterprise systems.
“This creates the ROI that the healthcare industry requires in their business model,” FLEXcon’s Koldan says. “Enabling the patient-safety and business-efficiency benefits will outweigh the incremental costs of the IT implementation.” FLEXcon provides polymer labeling solutions for medical devices and pharmaceuticals.
A technology which holds the promise of driving life-saving innovation to drug labeling is barcode-enabled medication administration (BCMA). BCMA is used to verify all medications electronically before they are administered to patients. Healthcare providers who implemented bar coding solutions report improved patient safety through the reduction of preventable medication errors.
A case in point is Mercy Medical Center (Cedar Rapids, IA), which reports having implemented a drug administration system called Bedside Medication Verification/electronic Medication Administration Record throughout the inpatient areas of the hospital. To ensure patients receive the right meds at the correct dosage, Mercy states that a nurse will use a handheld scanner to scan their wristbands and the medication to ensure they match. Mercy’s commitment to providing patient-centered care with a focus on quality and safety is the reason it implemented the bar coding system, the hospital says.
Fig. 5. Nosco’s multi-layer labeling. Credit: Nosco
New labeling solutions
The latest products from carton and label providers have enough white space to allow scanners to read the barcode properly, accommodate more useful information and remove any obstacles additional components would have on packaging line efficiencies. Methods of artwork layout, including color schema and visual structure, are being targeted to help reduce medication errors. Observers say this has triggered the popularity of multi-panel labels which enables information to stay with the primary package throughout its life cycle, making it an ideal choice when communicating patient adherence information.
These efforts fall in line with FDA guidance, which suggests surrounding the label with enough white space to allow scanners to read the barcode properly. The barcode should appear in a conspicuous location where it will not be difficult to read because of distorted text. To that end, Nosco offers a three-panel label called Tri-View and Fix-a-Form (FaF) multi-panel labels which address the needs of the consumer for improved clarity and ease of information access.
“The 3-panel labels are ideal when a relatively small amount of additional copy space is required, such as a ‘drug facts’ box,” Albrecht explains. “Fix-a-Form is used when a large amount of copy is needed for information such as patient usage instructions, diagrams and professional instructions.”
Although the label has to carry a lot of information and combine user friendliness with patient safety—which demands a high level of sophistication—it still needs to be easily integrated into the production processes at the pharmaceutical manufacturer and run smoothly on dispensing machines, observers say. MWV’s Shellpak and Dosepak adherence solutions are said to offer a label-friendly, large, flat space on both the front and back of the package that readily accommodates all required manufacturer labeling, as well as providing real estate for labeling by the dispensing pharmacy. Moreover, because the Shellpak and Dosepak medication cards are designed to slide out, but not be removable from the outer container, both manufacturer and pharmacy labeling are designed to stay with the patient through the duration of the dosing regimen, rather than being discarded, according to MWV.
“The ample space provided by this type of package configuration will allow for incorporation of new technology, such as what may be required by future track and trace legislation,” Le says.
Fig. 6. Flexcon’s shrink-wrap labeling for OTC products. Credit: Flexcon
Drugmakers are also seeking to optimize quality across all product lines by implementing cutting-edge vision systems, industry watchers say. Applying this added scrutiny to labels’ print quality is, in turn, requiring printers to boost their quality as well. For example, 3C Packaging reports having recently purchased a new, servo-driven UV press with an integrated LVS Vision System. “The system detects any blemishes or defects and removes affected items from circulation,” Hill says, “enabling our customers to maximize their production lines.”
Further developments designed to minimize the risks of medication errors involve the use of peel-off labels (POLs), an application utilized prominently in Europe. FDA recommends sponsors develop, whenever possible, a transferable or peel-off label for the commercial container of injectable products. This type of label can help minimize the use of unlabeled syringes because the label would be attached to the commercial container closure, present at the point of product preparation, and not be discarded as is the case with other auxiliary labels often provided with the carton.
POLs can also provide a clear identification of the drug or vaccine and variable data pertinent to the product. Schreiner MediPharm offers a broad portfolio of labels with peel-off parts; these labels contain all necessary product information and have one or more detachable parts which help to clearly identify the drug, all the way from dispensing to patient administration.
Industry members concur that product container labels and carton labeling should communicate information that is critical to the safe use of a medication from the initial prescription, to procurement, preparation and dispensing of the product, up until the time it is given to the patient. Poor label design can contribute to medication errors by making it difficult for healthcare professionals, caregivers, and/or patients to readily locate and understand critical safety information.