Purdue Pharma Blazes a Trail for Drug Security

Last fall, Purdue Pharma (Stamford, Conn.) took drug product security where no other company had ever gone before — putting radio frequency identification (RFID) tags on commercial pill bottles. At its Wilson, N.C. plant, Purdue began applying labels with one-inch tag inlays to every 100-count bottle of the painkiller OxyContin headed to distributor H.D. Smith and retailer Wal-Mart, two willing partners in the pilot project. A few months later, the same was done for bottles of its new painkiller, Palladone, at the company’s Totowa, N.J. facility.[Editor’s Note: On July 13, FDA asked Purdue to withdraw Palladone from the market for safety reasons. See sidebar below.]This has allowed Purdue to monitor the products as they move through production at Wilson and Totowa, and to coordinate with H.D. Smith and Wal-Mart to track and trace individual bottles throughout the supply chain — all the while gaining more robust information than would be possible with bar codes or other technologies.Other manufacturers have dabbled in item-level RFID — Pfizer is tagging some bottles of Viagra — but none to the degree that Purdue has. Purdue is driven by the desire for state-of-the-art product and brand protection. As narcotics, OxyContin and Palladone are highly attractive targets to drug diverters and counterfeiters, and drug abusers.The company is responding to a number of other factors as well:

• Wal-Mart’s mandate that, by scheduled dates, all products being shipped through its key distribution centers must have RFID verification, at least at the case level;
  
  
• FDA’s backing of RFID as a preferred means for drug manufacturers, especially those producing high-risk medications, to better control their products and supply chains;
  
  
• Pending legislation by states such as Florida requiring that drugs being shipped across their borders have valid “pedigrees.”

Purdue initially invested some $2 million to make its plants RFID-ready — installing equipment such as RFID reader systems by Northern Apex (Huntertown, Ind.) at various stages in production, then making sure they would read tagged bottles properly and with minimal interference from the surrounding environment. It also committed to spending 30 to 50 cents for every RFID device affixed to a bottle — in this case, basic read-only (i.e., non-programmable) Class O tags made by pilot partner Symbol Technologies (Holtsville, N.Y.). To date, more than 200,000 tagged bottles have been shipped.“We didn’t really prepare an ROI from a dollar perspective,” says Chuck Nardi, the company’s information officer. “Item-level tagging is great technology that we wanted to use and understand and feel like it will be beneficial in the industry going forward.”Tracking successIs it working? Yes, says Aaron Graham, chief security officer. The company has met its goals of performing 100% on-line verification of individual bottles in the plant and of those bottles once packaged in 48-count cartons, says Graham. It is also successfully using RFID capabilities to monitor product flow throughout the supply chain. And it is associating the electronic product code (EPC) data with other business transaction data to gain better oversight of shipments and leverage existing processes. “We have proved that we can use RFID to monitor and authenticate a product and protect the patient from counterfeit, adulterated, mislabeled drugs,” Graham says. “We now know it can work.”No one, least of all Purdue, views RFID as the cure-all for supply chain security. It is only one facet of the company’s comprehensive, multi-layered security approach for drugs like OxyContin and Palladone. In its facilities, Graham notes, Purdue employs closed-circuit TVs and “Vegas-style” surveillance cameras, puts color-coded, pocketless uniforms on workers, and uses advanced biometrics and the latest access controls, all in an effort to reduce the potential of internal product theft.When drugs leave the plant, the company’s transportation security protocol kicks in. Drug shipments are delivered by armored vehicles with armed drivers, tracked by GPS systems, and watched by independent countersurveillance experts.“This is what everybody should be doing now,” says Graham, a former undercover investigator for FDA. The biggest surprise for Graham is that organizations along the pharmaceutical supply chain have not yet grasped the impact that RFID will have. “Ten years ago when I was working for FDA we knew this technology was needed,” he says.Designing an RFID landscapeSymbol Technologies and Northern Apex have been the major equipment providers for the pilot. Symbol manufactures the RFID chips and inlays that are affixed to the OxyContin and Palladone labels.Northern Apex has supplied reading systems — including Symbol RFID scanners, an industrial PC and software, and an operator interface—used in manufacturing and shipping. Integrating the readers into production was the greatest manufacturing challenge Purdue faced. Handheld scanners were incorporated into receiving operations to monitor incoming raw tags for effectiveness. In addition, Purdue placed mounted, stationary reader systems:

• On the packaging line, after the label applicator
• At the case pack station
• At both inbound and outbound vault locations.

Once the equipment is in place and functioning, Northern Apex software relays data to SAP asset management and ERP applications. The key to hardware and software integration was getting representatives from packaging, IT, internet security, engineering and supply chain groups all involved in the process and meeting on a regular basis, says Nardi.A concern going into the project was the effectiveness of the RFID tags themselves. Tag technology, while improving, is still somewhat immature. Nardi says that 20% to 30% of the labels supplied for the pilot have experienced read failures, whether due to the design of the silicon chips, problems in equipping the chips with RFID antennae, or in applying the tag inlays to product labels.Purdue takes great pains to weed out dead or poorly functioning tags. It tests all tags (rejecting or recycling the bad ones) before and after they are applied to product labels at its label integrator, after they arrive at the Purdue sites as label rolls, after they are individually applied to bottles, and finally when the bottles are placed in cases.“We put quality control steps as early as possible in the process to vet out all the bad tags,” says Nardi. “We only start reading the data and collecting information when we’ve got 100% success rate.” Only a handful of the hundreds of thousands of bottles tagged have experienced tag failures after leaving the plant, Nardi claims.As tag chip and labeling technologies improve, tag yields are improving, says Phil Lazo, VP and GM of Symbol’s RFID infrastructure division. Just as bar coding and clothing store antitheft tags had their growing pains, so will RFID technology, Lazo and experts agree.Capturing and managing the dataEquipment notwithstanding, what distinguishes Purdue’s RFID pilot from what are considered “slap and ship” projects is how data is gathered and put to use. “Ours is not just a system of tags and readers,” says Nardi. “That EPC number alone is just a serial number like a license plate. If you don’t tie it into your back-end ERP and other software systems and associate it with key data points, then it’s not that valuable.”SAP has been an integral partner in the pilot. Its Auto-ID infrastructure provides the middleware layer that sends data (through its XML translation engine XI, or Exchange Infrastructure) into an event manager in supply chain management component. The EPC data resides in this environment, and can be connected to the R/3 ERP environment.The pilot has spurred SAP to upgrade its RFID offerings, such as configuring its R/3 ERP system to better accommodate RFID data, says Jim Sabogal, who manages SAP’s life sciences business. In turn, vendors are aligning RFID technologies with the software giant. Sabogal cites Zebra Technologies’ (Vernon Hills, Ill.) new RFID printer line that functions out of the box with SAP. “When we first started working with Purdue, we had to have new drivers and printers and all sorts of thing,” Sabogal says. “When you’re an early adopter, there are a lot of things that don’t work quite well.”Sabogal credits Purdue for blazing a trail. “If you’re a pharma company to come along, you’ll use software that Purdue has already proven,” he says. “Our larger customers are now looking at RFID and saying, ‘We can probably do this in one plant, but what happens when I have 30 plants and 20 distribution sites?’”Taking this step will depend upon firmer standards from EPCglobal, the body designated to develop standards for RFID equipment and protocols. “We have the infrastructure to take data from around the world, consolidate it and have high visibility within the whole organization,” Sabogal says. “Everyone is sort of waiting for EPC to make its standards decision as to how they’re going to handle data. That’s what’s going to drive pharmaceutical companies and software vendors as well.”Adding e-pedigree to the mixA sure sign that the Purdue pilot is progressing is that two more partners, Unisys (Blue Bell, Pa.) and SupplyScape, Inc. (Cambridge, Mass.), were recently brought into the mix to provide electronic pedigree capabilities to the shipped product. Unisys will lend its ES7000 enterprise-class data management platform, while SupplyScape will contribute its e-pedigree software package.With this added wrinkle, Purdue and H.D. Smith will not only be able to track and trace OxyContin bottles throughout the supply chain, but also be able to generate paperless documentation regarding which individuals handled and signed off on the product, when they did so, which dock doors that the bottles traveled through, and so on. The addition means that RFID becomes not just a supply chain and inventory management tool, but also one for product authentication and compliance.The e-pedigree software integrates data from both the ERP and RFID applications, and processes it into authenticating documentation for each individual bottle, says Peter Spellman, senior VP of products and services for SupplyScape. A company such as Purdue can also maintain real-time surveillance over all product shipments as they change hands, using XML data interfaces. “What you have is events being percolated up to a responsible individual” at any given time, Spellman says.By 2006, Florida and several other states will have laws dictating that all drugs passing through them have credible paper or electronic pedigrees (for details, see "The State of E-Pedigrees"). While RFID is not mandatory for establishing pedigrees — barcodes are fine — it is by far the most efficient and robust technology available, Spellman says.The standards debateHow quickly Purdue takes its lessons learned and begins using RFID for any or all of its other products will depend upon interest from other distributors and retailers that they do so. It also wants to be sure there will be enough tags available. The tag market, in terms of both supply and demand, has been hampered by the lack of widely accepted equipment standards due to an ongoing debate within EPCglobal and its health care and life sciences contingent over which operating frequency, 915 MHz or 13.56 MHz, is best for item-level tags and readers.EPCglobal has approved “Generation 2” standards for 915 MHz ultra-high frequency (UHF) equipment, and the standards are expected to be adopted soon by ISO without major changes. This has encouraged RFID OEMs to develop and market much-needed Gen 2 products. ISO standards already exist for 13.56 MHz high frequency (HF) equipment.Purdue is using UHF tags and readers based on Wal-Mart’s original recommendations. However, many in the pharmaceutical industry feel that HF equipment is better suited for item-level pharmaceuticals. There are concerns that UHF signals may, for instance, interfere with existing hospital equipment, while HF tends to have higher accuracy and better performance near metals and liquids.Until the dust settles surrounding the HF/UHF debate and until ISO standards are set, tag production will lag. “You don’t want to start shipping product and not have tag availability,” says Nardi, an active EPCglobal participant. “It has not been an issue for us yet. Our volume hasn’t highlighted any problems, but I’m sure the potential is out there.”Symbol’s Lazo says his company is readying its Gen 2 tags for greater production. More importantly, Lazo says, it has developed its multiprotocol readers so that they may read Class 0 (read-only) and Class 1 (programmable) tags from either Gen 1 or 2 — an ability that will be necessary to accommodate RFID projects across the supply chain with multiple partners, and lead to the advancement of critical “plug-and-play” technologies.Another challenge for Purdue will be to maintain cycle times while broadening RFID implementation. Cycle time slowdown has not been a significant issue due to the limited scope of the project at present, Nardi says. The company has been able to apply tags, read them, and check for failures while maintaining a typical 120 to 130 bottle-per-minute line speed. Currently, it takes three to five seconds to read 48 bottles, Nardi says.As volumes increase, Purdue will need to reconfigure how it uses RFID downstream. At present, each of the 48 bottles in every case is being read from manufacturer to distributor to retailer. Cases are serialized with bar codes. “What we’d like to do next is tag the cases so we’ll be able to associate the tag on the case with the bottles inside,” Nardi says. “Today, there’s still a lag time to read 48 bottles in a case.”That would likely involve an integrated mix of equipment at different RFID frequencies, he says — 13.56 MHz at the item level, and 915 MHz at the case and pallet level due to UHF’s longer read ranges.Keeping knowledge in-houseWhatever the next step, Purdue has prepared itself for moving ahead by developing its internal expertise on how to run an RFID-enabled operation. It has made a conscious effort to involve as many people as possible in the plants in the design and feedback phases, and to limit its dependence upon outside consultants.“RFID isn’t really a type of department,” explains Nardi. “It’s part of IT, part of engineering, part of packaging, and all the groups need to work together. We could have hired an RFID group, but it made sense to keep the understanding and intellectual capital with us.”

Purdue Ceases Palladone Manufacturing Citing safety concerns, FDA has forced the drug off the market By Gregg Carlstrom Purdue Pharma L.P. is halting production of its prescription painkiller Palladone, amidst new FDA concerns about the drug’s side effects. July 13, FDA asked Purdue to voluntarily remove the drug from the market, citing concerns that the drug could have potentially fatal side effects if mixed with alcohol. Purdue had disclosed information regarding alcohol-related dangers — that alcohol could accelerate the rate of release of the drug’s active ingredient, hydromorphone — when seeking regulatory approval for Palladone last winter. The drug’s label carries a warning advising doctors and patients of the risk. A recently completed study by Purdue suggested that the combination of Palladone and alcohol could be deadly. To date, there have been no documented cases of patients experiencing life-threatening side effects. But in light of the new study, the Agency said it had no choice but to recall the drug. “When FDA approved Palladone, the Agency had evidence from laboratory studies that alcohol could accelerate the release of hydromorphone from Palladone capsules,” the Agency said in a press release. “Neither the Agency nor Purdue Pharma anticipated that this would be life-threatening to patients themselves.” Purdue has begun work to reformulate the drug and reduce the risk of a deadly alcohol interaction. Purdue’s CEO and president, Michael Friedman, says his company has always made a policy of complete disclosure to FDA. “We acted responsibly and worked closely with the FDA in launching Palladone on a limited basis with a rigorous risk management program,” said Friedman. “We will continue to work collaboratively with the Agency to resolve all open issues and to reintroduce the reformulated product as soon as possible.”