FEATURE
Editor
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Some technology providers argue that drug security should exist on multiple levels. NanoGuardian offers nanotechnology for use on tablets, capsules, and packaging.
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Spurred on by state and federal interest in securing the drug supply chain with electronic pedigrees, many pharmaceutical companies are looking at item-level serialization to uniquely identify products. They are studying how either bar codes or RFID (or both) can be used on packaging to convey unique identifiers that could be used in electronic pedigree programs. Most companies are still in pilot stages.
But are electronic pedigrees all you need for securing the supply chain? Some industry stakeholders believe so, given the promise of item visibility. If you tag or mark a salable unit with a unique serial number and track that numbered unit through the supply chain, you can follow it to its eventual disposition. If another unit pops up somewhere with that number or with an unregistered number, that unit would have a questionable pedigree and be subject to further investigation.
Other experts, however, suggest complementing the track-and-trace functions of unique IDs and electronic pedigrees with authentication technologies. They argue that pedigrees track numbers not products, and therefore product packaging needs to be verified in some manner. Further, there is some debate as to whether the product itself needs to be authenticated. There is also discussion about who should be carrying out authentication—authorities, company auditors, pharmacists, doctors or nurses, even patients.
As these debates unfold, pharmaceutical companies are still left with deciding what weapons to use to fight drug counterfeiters and diverters. The answer may lie in building a well-stocked arsenal.
“The promise of a secure supply chain is with both track and trace and authentication,” says Gregg Metcalf, industry market manager, strategic initiatives, for Nosco. “Until a complete RFID infrastructure can be put in place to systematically electronically manage drug product distribution, I believe authentication tools will be required with sampling-based manual processes as a bridge solution.”
STANDARDS
FDA is charged under the FDA Amendments Act of 2007 (FDAAA) with developing standards for numerical identifiers and for authentication tools. The agency invited industry comments earlier this year. Some respondents spoke of track and trace and authentication as being distinct functions; others did not.
Many drug manufacturers expressed interest in the identification standards developed or under development by GS1, namely the Global Trade Item Number (GTIN) or the Serialized Global Trade Item Number (SGTIN). “The standardized numerical identifier should be comprised of random recognizable codes based upon the GS1 EPC global standards rather than on recognizable characteristics,” Abbott wrote to FDA. Further, “tracking and tracing of pharmaceutical products is possible if the appropriate visibility is designed into the electronic system to support the discovery process. Proof of delivery, expiration management, recall management, anticounterfeiting capabilities, expiration notice, and alert management can only be realized by [ensuring] appropriate trading partner visibility to the data captured during transactions in the supply chain.”
TAP Pharmaceuticals expressed that “electronic pedigree is the cornerstone in meeting FDAAA’s mandate because it can be used with lot-level information to secure the supply chain now for all products, and when standards exist for numerical identifiers, Standard Numerical Identifiers (SNI) can be integrated with pedigree to provide additional security for those products most at risk . . . an SNI should comprise the following elements: NDC-related number, such as the GS1 GTIN; a unique serial number (sequential or random to be determined by the manufacturer); and flexibility to allow companies to use additional security technologies (e.g., public key/private key encryption).”
Pfizer wrote that “authentication of the serial number found on the product packaging can be achieved with various technologies including RFID, 2-D bar codes, linear bar codes, etc.” In addition, packaging can also be authenticated “with other overt and covert technologies such as color-shifting ink, holograms, etc. Such technology may be sufficient for many products that might not require serialization and tracking and tracing throughout the supply chain. It is our belief that FDA should not mandate the use of any particular technology but rather leave this to the market and individual organizations to decide.”
A supporter of GS1 standards, Johnson & Johnson explained to FDA that serialization and track and trace will “allow each supply-chain partner downstream from the manufacturer to authenticate the package only.” However, “these technologies will not single-handedly eliminate the threat. Johnson & Johnson utilizes a variety of counterfeit-resistant technologies including overt, covert, and tamper-evident packaging and labeling features. These technologies make our products more difficult for counterfeiters to reproduce accurately and are also useful for assessing the authenticity of drug products.”
Amgen, too, sees the safety in a multitiered approach. “Amgen recognizes that the deployment of a well-designed serialized, track-and-trace system could help to ensure the authenticity and proper distribution of medicines,” the company wrote to FDA. “Amgen supports the ultimate adoption of a sealed and serialized approach based on the use of legally protected sealing of outer packaging
to ensure the physical integrity of the packaging medicine and serialization of the package to ensure the source and authenticity of the packaged product.”
Further, Amgen argued that “FDA should allow manufacturers to select the technologies for use in protection of their products . . . while Amgen has implemented packaging lines designed to apply our optically variable, tamper-evident carton closure label . . . other companies may have chosen to use very different technologies.”
Tim Marsh, Co-Chair GS1 Healthcare, explains that an “anticounterfeiting program is somewhat independent of a pedigree program. Most pharmaceutical companies with high-risk products have anticounterfeit platforms in place for authenticating products. A pedigree program simply expands on that platform and directly involves the other major players of the supply chain in the process. A global standards–based pedigree platform offers benefits over proprietary anticounterfeit platforms. Verifying a unique serial number—i.e., the SGTIN—with supply-chain partners allows distributors and retailers to authenticate the package. The visibility and detection of counterfeit product has the potential to occur very quickly if everyone participates in a pedigree program.” But, he cautions, “authenticating the data in the SGTIN on the package doesn’t mean that the container has authentic product.”
Marsh adds that drug companies “trip up with a lack of standards or ambiguity in standards. The best thing is for companies is to get involved in standards development regarding automatic identification. It is a unique opportunity for pharmaceutical companies to work in a collaborative environment towards a common goal.” However, he cautions against mandates for specific anticounterfeit technologies used for authentication. “Technology evolves quickly, so legislation could become outdated soon after it is enabled,” he says.
MORE THAN A NUMBER?
The International Authentication Association (IAA) wrote to FDA to encourage standards for authenticating pharmaceuticals. The group is working with the European Standards Committee (CEN) to devise a Protocol for the Detection of Counterfeits. “As these standards are completed and adopted, they will, we believe, benefit the work that both the EC and the FDA are now embarked upon,” IAA wrote.
IAA sees the security benefits of item serialization, but only if layered with “authentication features directly associated with the physical item,” the group expressed to FDA. Appropriate authentication features would “not require access to databases” and include “holograms, optically variable inks, taggants, invisible inks, etc.”
Serialization is not a complete solution, the group argued, because some healthcare supply-chain participants without computers or cell phones wouldn’t be able to access pedigree data. In addition, pedigree databases could be vulnerable to unauthorized use or duplication and potentially mislead buyers or pharmacists.
Mark Davison of IAA member SICPA said that “for systems that verify a serial number by phone, with little or no security, fake call-in systems could be created in almost a parallel universe of authentication.” He spoke at the Fourth Global Forum on Pharmaceutical Anticounterfeiting held June 4–6 in Washington, DC.
“Packaging ID is only one step,” he told attendees. “Physical and material security is also needed.” SICPA provides security inks for banknotes and labels as well as other complementary technologies. “Pharma doesn’t need to relearn—you can look at other industries. The tobacco industry can code, track, and authenticate relatively cheap products in a cost-effective manner.”
Jim Rittenburg, vice president, healthcare and life sciences, for Authentix, also spoke at the forum. He spoke of “confusion between digital verification and physical authentication.” Davison agreed, asking, “How do we move from tracking something to making sure what we are tracking is the right thing?”
IAA’s suggestion is the use of a packaging seal defined as “a tamper-evidencing closure or seal with product authentication components [that] cannot be copied, removed, or altered once affixed by the manufacturer.”
Rittenburg urged attendees to consider “mass serialization at the salable unit level along with authentication features in the package.” In other words, develop a “layered” solution, he advised. “Different features can be layered for different points of authentication.”
Part of the counterfeiting threat may come from repackaging. “There is very little oversight,” said Rittenburg. “We need to eliminate it or reduce it.”
IAA discourages product repackaging and recommends that “primary and secondary packaging accompany the product from the manufacturer to the consumer.”
“We should not allow repackaging,” said Davison. “Why would companies invest in packaging if it ends up in the trash?”
Rittenburg advised attendees to increase use of unit-of-use packages, such as bottles with regimen counts, which could be distributed by pharmacists without having to be broken down further. Authentication features could be built into these packages.
IAA suggests that “qualified auditors be identified or trained to ensure compliance with GMP and/or GDP.” It does urge “public awareness for any security initiatives,” it wrote to FDA. “We encourage the use of packaging elements that can trigger suspicion in all who handle the pack, not just authorized inspectors.”
However, Davison cautioned against relying solely on consumer authentication. “It is not their responsibility,” said Davison. “Consumer-empowered systems can give a false sense of security.”
David Howard of Johnson & Johnson and chairman of IAA spoke of the importance of track and trace. “I cannot authenticate what I cannot locate,” he said. However, he cautioned against adoption of a Federal Express approach to supply-chain security. “FedEx can tell you where a package is and has been, but it cannot tell you whether it is authentic.”
Speaker Dean Hart, executive vice president for NanoGuardian (Skokie, IL), told attendees that “every time you add a layer of security, you remove a layer of bad guys.” He urged both on-package solutions as well as on-dosage solutions to maximize brand-protection effectiveness.
Hart sees a way for authentication to link back into serialization. “Authentication is wonderful, but can you track it back?” he asks. His firm is using nanotechnology on dosage that can be used to authenticate and trace tablets, capsules, and vial caps back to their original packaging. Without specifying how the technology works, Hart says that unlimited amounts of information about an item can be included in every tablet, capsule, or vial cap using NanoGuardian’s NanoEncryption technology. Data can then be fed into databases and utilized in the fight against counterfeiting and illegal diversion, he says. The multilayered security features within NanoEncryption technology provides security features at the overt, covert, and forensic level. “About 350 of our NanoCodes fit in the width of a human hair,” he says. No material, however, is added to the product, he added. In May, FDA issued approval to a NanoGuardian client to use its NanoEncryption technology as an on-dosage, brand-protection technology as part of a Supplemental New Drug Application, he reports.
GOVERNMENT MANDATES?
The global forum highlighted the success of the authentication program put in place by the Ministry of Health in Malaysia. Use of a serialized hologram called the Meditag was mandated in May 2005 for nonparenteral prescription and over-the-counter drugs and in July 2005 for parenteral drugs. OTC external-use-only products, vaccines, and biologicals are exempt. Siti Aida B. Addullah explained how the hibiscus flower–bearing hologram label employs registration numbers assigned to specific products. The 8 x 16–mm sized labels are supplied by Mediharta Sdn Bhd utilizing a hologram label produced by Hologram Industries. Officers at pharmacies are trained to recognize fakes. “The program has encountered fake holograms on fake products,” she explained. “But we found the counterfeits this way.”
Penalties may serve as a deterrent to counterfeiting and tampering. The first offense brings a sentence of three years; the second offense, five years. Malaysia is currently strengthening enforcement by increasing manpower and stepping up public awareness of the program with advertisements, said Addullah.
Ed Dietrich of Hologram Industries says that Malaysia’s program is an example of a well-conceived and well-executed program. “There are benefits to the entire chain. The Malaysian government’s commitment all the way down the supply chain has made a difference on a large scale,” says Dietrich, formerly director of the Americas for Reconnaissance International, which acts as the Secretariat for the International Hologram Manufacturers Association. Such a program “is being considered by other countries in the developing world, and it is not necessarily impossible for the United States.” FDA has got to step in with standards and ultimate guidelines on authentication and pedigree, he adds.
LAYERING UP
Dietrich cautions FDA and state governments not to rely solely on a pedigree system. “In this area, government has fallen into the habit of looking for one tool,” he says. However, “e-pedigree alone will not do the job. It will have holes in it,” he says. Authentication technology advocates are confident that such tools can make a difference, but they admit that they are not foolproof, either.
The ultimate test about what works and what doesn’t may lie in practical utility. GS1 Healthcare director Ulrike Kreysa is concerned about potentially involving pharmacists in product authentication using proprietary solutions. (Kreysa spent 11 years as a hospital pharmacist and another 8 years as a retail pharmacist.) “Be aware that there are pharmacists who need tools to verify pharmaceuticals as a matter of daily business,” she says. “They need a practical, easy process that operates across businesses and across the world. It cannot be too complicated, and it cannot be individual technologies for individual products.”
Concludes Marsh: “Consider multiple technologies, but know that there are always weaknesses that will be exploited.”
Strength, perhaps, may come from a combination strategy—package visibility in the supply chain through use of a common electronic pedigree system along with product authentication by private detection using proprietary technologies.
