FDA Revisits RFID and Drug Pedigrees

The US Food and Drug Administration must decide by the end of the year whether to implement a rule that requires drug manufacturers to have a system in place that can track a drug's pathway from the manufacturer to the final dispenser, even if it means starting with an outmoded paper-based pedigree system. The policy aims to thwart drug counterfeiting, which is on the rise around the world, threatening public health as well as manufacturer revenues. Although FDA has delayed action, individual states and major retailers are responding by implementing their own drug pedigree requirements. Manufacturers are participating in pilot tests of new systems to see how well they can track drugs through the distribution chain, as well as prevent tampering and identify fakes. So far, most solutions appear costly but promise to earn their worth by modernizing inventory and distribution systems and avoiding legal and regulatory problems.

Jill Wechsler

Pedigrees on hold

FDA held a public workshop in early February to examine what progress has been made in implementing electronic track-and-trace technologies during the past two years, focusing particularly on incentives and obstacles to establishing a radio frequency identification (RFID) system (see Glossary of security and anticounterfeiting terms). As part of its anticounterfeiting objectives, the Prescription Drug Marketing Act of 1987 (PDMA) requires unauthorized wholesalers to provide purchasers with a statement (or pedigree) presenting a history of prior sales of the drug and the names and addresses of parties to these transactions. The legislation also aimed to control drug counterfeiting and illegal diversion by requiring states to license wholesale distributors of prescription drugs and by controlling drug sampling. Those provisions were implemented years ago, but wholesalers objected strongly that a pedigree system would be costly and impossible to establish. FDA agreed to delay implementation until manufacturers, distributors, and pharmacists could develop a workable approach.

By 2004, the solution appeared to lie in establishing an electronic tracking system that uses RFID technology. An FDA counterfeit drug task force issued a report that examined technological and policy developments related to drug counterfeiting and concluded that the agency should postpone the pedigree requirement once more to provide time to implement an electronic tracking system by 2007.

Nonetheless, at the FDA workshop in February, participants acknowledged that the implementation of a workable tracking system using RFID technology is still years away. Progress has been "disappointing," commented FDA Deputy Commissioner Scott Gottlieb at a drug anti-counterfeiting forum sponsored by the Parenteral Drug Association (PDA, Bethesda, MD, www.pda.org) this past month. He noted a lack of agreement on key issues such as who pays for RFID and who owns transaction data.

Now, the agency's Counterfeit Drug Task Force, which is chaired by FDA Associate Commissioner for Policy and Planning Randall Lutter and Associate Commissioner for Regulatory Affairs Margaret Glavin, is scheduled to report back in May about whether to delay the pedigree rule once more or to implement the requirement, possibly with some changes.

With pressure mounting to do more to protect the nation's drug supply from counterfeiting, tampering, and diversion, another stay seems unlikely. The task force will lay out the options, examine available tracking and authentication technology, describe the multiple levels of protection needed to better secure the nation's drug supply, and provide additional policy guidance to spur all parties in the supply chain to move forward. Policy makers now recognize that RFID is not a magic bullet and that an effective system requires universal standards, new information systems, and access to a range of protective strategies.

Glossary of security and anticounterfeiting terms

Divergent viewpoints

One problem is that manufacturers, wholesalers, and pharmacists disagree about how best to address these issues. Pharmaceutical companies want FDA to implement the pedigree policy, predicting that this will force everyone to agree on strategies for securing the supply chain. Companies support joint efforts to harmonize standards for data transmission, but want control over how they use those standards.

Pharmaceutical companies also want to stick with linear barcodes as the basic method for identifying drug products, keeping options open to provide more information through more sophisticated identifiers. FDA currently requires drugs and biological products to have linear bar codes with the product's national drug code (NDC) on their labels, but expiration dates and lot numbers are discretionary.

Wholesalers and retail pharmacists insist that any national drug pedigree system must be electronic. The Healthcare Distribution Management Association (HDMA, Arlington, VA, www.nwda.org), which represents national drug wholesalers, wants FDA to phase in an RFID system using electronic product codes (EPC) and mass serialization at the item level. HDMA opposes two-dimensional bar codes that must be scanned directly; RFID chips can be read remotely, making it unnecessary to open packages to track a product. Wholesalers also are lobbying for national licensing standards to replace multiple state requirements.

Similarly, retailers would like anticounterfeiting initiatives to focus on high-risk products. They advocate broader public education and awareness efforts, and they support stricter licensing requirements for wholesalers by state pharmacy regulators.

Outside involvement

Added pressure for action comes from a growing number of states that are adopting their own drug pedigree requirements. Florida enacted a law in 2003 to discourage drug counterfeiting and diversion by requiring wholesalers to provide paper pedigrees for prescription drugs; it becomes fully effective in July 2006. California expects to implement a drug pedigree policy in 2007 or 2008. It envisions an electronic tracking system that can transmit extensive product data on all drugs moving from a manufacturer through final sale to a pharmacy or dispenser.

In addition, major retailers such as Wal-Mart (www.walmart.com, Bentonville, AR) are requiring suppliers to ship goods with RFID tags to certain warehouses and stores. The program calls for identifiers to be added to pallets and cases, as opposed to individual products, and primarily involves controlled substances in the pharmaceutical field.

Members of Congress also are stepping up involvement in drug security activities. In March, representatives from both sides of the aisle introduced legislation establishing a time frame for phasing in electronic tracking of prescription drugs. A bill sponsored by Rep. Dan Burton (R-IN) requires RFID tracking of the 30 most frequently counterfeited drugs (to be identified by FDA) by Dec. 31, 2007; the provision extends to all drugs by 2011. Legislation proposed this past year by Rep. Steve Israel (D-NY) goes even further in requiring paper pedigrees until RFID technology is fully established.

Several pharmaceutical manufacturers have launched pilot tests of RFID tracking systems, primarily for products targeted by counterfeiters or other illegal operators. Purdue Pharma (Stamford, CT, www.pharma.com) has tested an electronic pedigree system to track and prevent diversion of "OxyContin." Following pilot tests that shipped tagged tablets from manufacturing plant to distributor HD Smith (Springfield, IL, www.hdsmith.com), Purdue plans to fully implement an electronic pedigree program this year.

Pfizer (New York, NY, www.pfizer.com) has been testing RFID tagging of "Viagra" (sildenafil) to gain experience with mass serialization and EPC capabilities. In January, the company announced that it would add RFID–EPC tags to all Viagra distributed in the United States The company acknowledges that this current tagging system may help distributors and pharmacists authenticate genuine product, but it does not have broader track-and-trace capacity because much of the supply chain is not part of the program.

Multiple layers

A system that fully protects the US prescription drug supply from illegal use requires information systems that can read the data on the tags and make it accessible throughout the distribution system. Additional strategies are needed to distinguish genuine from bogus products and prevent tampering, including increased surveillance and enforcement by the government. Manufacturers and other parties are taking these steps to move the process forward.

Establish standards for electronic data communication. EPCGlobal (Lawrenceville, NJ, www.epcglobalinc.org), an international, nonprofit organization, has formed a healthcare action group to develop e-pedigree standards on the basis of a universal interchange format that trading partners can use to send and receive pedigrees in a secure manner. Standards address pedigree messaging, item-level tagging, serialization, RFID frequencies, and network security. Most leading pharmaceutical manufacturers are involved, along with large distributors, retail pharmacies, hospitals, and FDA. Pedigree data elements will include information about the drug product, the specific item (lot number, expiration date), date of transaction, and trading partner.

Gain consensus on data management, storage, and access. A key issue is whether all the transaction information should be stored in a single central database or throughout the distribution network. Related concerns are who should have access to what information. Manufacturers propose that data on package units be routed to distributed databases that can signal a dispensing site in real time that the identification number is authentic.

Use diverse authentication technologies. Manufacturers are adopting a range of strategies to protect drugs from illegal copying and tampering. Various inks and coatings can be used to identify genuine packages, blister packs, and individual pills. Overt technologies include color shifting inks and holograms that can double as an antitampering seal. More sophisticated covert technologies—invisible chemically reactive markers and quantum photonic markers that show up under certain lights—are more difficult for counterfeiters to detect and copy. Desirable technologies have minimal impact on manufacturing processes, are easy to authenticate in the field and can be applied to multiple products and packaging components to support a corporate approach to product security across brands and regions.

Test for effect of tags and markers on pharmaceutical and biotech products. Although most inks and colorings used on tablets and drug packaging do not cause adulteration, the heat from RFID tagging systems could have thermal effects on chemical bonds in some products.

Seek additional FDA guidance. Manufacturers hope that FDA's May report will contain further advice about how to develop unique identifiers for drug packages, handle transaction data and whether any colorants or other authentication technologies are likely to effect product dissolution, stability, or identification.

Address patient privacy. RFID tagging raises the prospect that information about an individual consumer's drug use could be fed into a data system without the patient's permission or knowledge. The Federal Trade Commission (FTC, Washington DC, www.ftc.com) has been examining how electronic data that can be read from a distance could lead to surreptitious information collection.

Develop new business models and policies. Although RFID and authentication methods may appear too costly for all but the most vulnerable products, these strategies may pay off for manufacturers by improving supply and distribution systems, enhancing public confidence in company products, and avoiding costly lawsuits from consumers who are harmed by an adulterated version of the company's product. Lack of internal security measures and failure to adequately monitor products through the distribution system may create legal and regulatory problems for manufacturers in the future.

Beef up enforcement. FDA points to a rising number of counterfeit drug cases brought by its Office of Criminal Investigations (OCI) as a sign that the agency is taking drug diversion seriously. The Department of Justice (DOJ) also is expanding efforts to combat drug counterfeiting as part of its campaign against crimes involving intellectual property protection.

More than RFID

Although electronic track-and-trace still dominates discussions about effective prescription drug protection, there is a growing realization that RFID is primarily a supply chain management tool and is not very useful in product authentication.

RFID currently is the most advanced tracking technology, commented FDA's Gottlieb, but he noted a need to pursue a multilayered approach that includes use of two-dimensional bar codes and other technologies.

Gottlieb also acknowledged a need for stiffer penalties on lawbreakers and expanded enforcement and detection efforts. And, he suggested that the government may look for new ways to encourage drug security methods. One idea, he suggested, might be to require authentication technologies on drugs purchased for the national stockpile; a case could be made that product tracking would be important for medicines distributed broadly during a national emergency.

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, jwechsler@advanstar.com