The lettering above the entrance to the Food and Drug Administration’s main building in suburban Maryland says Naval Ordnance Laboratory, and on February 15, it almost seemed like a warning to anyone entering for a meeting held to advise the FDA on pharmaceutical packaging track and trace systems. Industry executives certainly detonated some rhetorical bombs during the two-day meeting.

At one point, Jim Dowden from Genentech strode to one of the microphones in the audience during a Q&A session and prefaced his remarks by saying he promised others there that he would keep his mouth shut, but couldn’t hold himself quiet. “When would you like that by?” he asked in exasperation, implying that the FDA would be requiring track and trace of drug packages at some set date, which is not the case (at least not yet).

Mr. Dowden’s question underlined some of the confusion at the fully-subscribed, two-day workshop attended by 130-plus industry figures. Connie Jung, senior policy advisor for pharmacy affairs, said she had to turn people away. Rick Seibert, vice president, new business development, Sharp Corporation, tried to register six weeks prior to the workshop and was surprised to discover he couldn’t get in. Sharp is a top-tier contract packaging firm in the U.S. and is working with a number of pharma companies on serialization. Some of those clients large pharma companies with their own manufacturing facilities, while others are “virtual” drug companies that contract out manufacturing, packaging, distribution and everything else (except R&D). Sharp prints standardized numerical identifiers (SNIs) on 2D barcodes on the unit-of-use package and also on the larger carton, which contains numerous packages, aggregates the data, authenticates it and then ships that data to the customer for internal use.

“Trying to get in to that FDA workshop was like trying to get a seat at a new restaurant,” Mr. Seibert explained. “If it’s that crowded, you assume the food is good.”

If the FDA is in fact cooking something up it is not cuisine but rather standards that are seen as the forerunners of a federal requirement. The Food and Drug Administration Amendment Acts of 2007 requires the FDA to publish item-level track and trace standards for interoperability, authentication and data management but includes no deadline for their publication. That law does not, however, give the agency the authority to require pharmaceutical companies to track and trace their packages.

However, such a requirement appears to be a certainty because the FDA is being pressured by a 2015 California deadline that requires manufacturers to provide an item-level e-pedigree for half their drugs going into the state. The second half of all products have to be “tagged” by January 2016, and wholesalers must accept and pass e-pedigrees six months later, with pharmacies having to do so by July 1, 2017. But Virginia Herold, executive officer at the California Board of Pharmacy, appearing at the FDA workshop via video conference from California, said, “We need a federal solution, although I’m not sure when that will start.”

The FDA obviously believes it needs to set track and trace standards first and worry about a federal mandate later. It is not clear whether the FDA needs a congressional grant of authority to require pharmaceutical item-level package track and trace, or whether it could do so under its current administrative authority to prevent the adulteration of drugs. Ilisa Bernstein, acting deputy director of the office of compliance at FDA’s Centers for Drug Evaluation and Research (CDER), replied to a question on that score with, “I will defer answering that right now.”

At the moment, there are very few companies ready to meet the California requirement, much less a more robust track and trace requirement at the national level. The first step in either case is for a pharmaceutical manufacturer to print a unique identifier on each unit of use package as it comes off the packaging line, and then aggregate that number and a second unique number on the carton into which numerous packages are placed. Then that data has to be authenticated, and uploaded to a corporate database equipped with software licensed from a company such as Axway or SAP. That data can be used to create an e-Pedigree, an electronic document for a particular shipment which is digitally passed from the manufacturer’s database to, for example, a third-party logistics company, which inputs its own information and then passes the digital shipping document to a wholesaler. The wholesaler may disaggregate the cartons on a pallet, decommission some of the data, create a new event, send that back to the manufacturer to update the e-Pedigree, before the wholesaler passes the revised e-Pedigree to a pharmacy or hospital, which authenticates it.

Few companies today are serializing unit packages, much less creating data repositories or e-Pedigrees, and then passing them on. In part, that is because standards for doing so are murky, the California deadline is still a ways off, and companies are hesitant because they want to see whether the U.S. endorses full track and trace standards that may be developed by GS1, the international organization, and which could then be adopted by countries around the world.

Right now, even the e-Pedigree standard the GS1 adopted in 2007 is under fire. That was rushed into final form to meet the needs of a Florida law that was going into effect at the time. Ruby Raley, director, health care solutions, at Axway, explained that the document pedigree management system standard adopted by GS1 focuses on collecting data on the chain of custody of a package. It does not provide information about the physical location of the package at a particular moment in time, based on a standardized numerical identifier (SNI). The FDA published a guidance document in 2010 advising companies on how to create an SNI.

GS1 has been working to finish a suite of more robust standards that would meet the FDAAA requirements for track and trace of item-level packaging. However, some distribution chain participants have criticized GS1 for being insular, too heavily influenced by big pharma and unresponsive to the needs of smaller players in the chain, particularly rural and independent pharmacies and some hospitals. Bill Fletcher, managing partner, Pharma-logic.com, worked for Systech when that company developed its e-Pedigree solutions and performed pilots for Pfizer and Purdue. He is currently assisting two pharma companies, including a $17 billion company with global operations seeking to comply with emerging standards for traceability around the world. GS1 basic memberships start under $1,000 for entrepreneurs, with the largest pharma companies paying five figures for multiple services. Pharmalogic is a member, but Mr. Fletcher has mixed feelings about GS1. “They are open to new ideas but it would be easier to develop standards for pharma if we didn’t have to contend with their bureaucracy,” he stated. “The weekly participants in the workgroups are from very big pharma, wholesalers and a handful of solution providers. In fact, my joining, because I am an unbiased subject matter expert and consultant, required special approval.”

Pharmaceutical manufacturers that started serializing packaging lines five years ago in response to the California e-Pedigree requirement struggled with the initial tight timelines for serializing their drug products before the California Board of Pharmacy extended the deadline to 2015. That is true of the medical diagnostics division of GE Healthcare. In its early pilot programs, GE appended a manufacturing site prefix and lot number to the serial number data field to ensure that identical serial numbers not be printed on packages from different packaging lines. Today, GE is ready to “push the button” in Cork, Ireland on its first complete packaging line serialization program. It has taken a different tack this time, eliminating the “intelligence” it had embedded in serial numbers it printed during its early California pilot runs. GE will have full control over serial number allocation through a fully functional serialization infrastructure. The Cork plant produces contrast media products used in conjunction with x-ray and MRI devices. Once the Cork packaging line is fully functional, perhaps by the end of 2011, GE Healthcare will move to serialize its 12 lines in Norway, Ireland, and Shanghai, said Gordon Glass, director of manufacturing project management. GE chose Optel Vision for the packaging line serialization, and is now deciding between two vendors for GE’s EPCIS data management system.

Jean-Pierre Allard, product manager, serialization solutions for OptelVision, said the FDA’s workshop illustrates that the serialization standards are still evolving, which the company took into account when it developed its serialization software. “We designed it in a way that many configurations related to standards such as the label layout can be modified directly through the HMI (human machine interface) so that the users can easily adapt the systems to new standards,” Mr. Allard explained.

The FDA, in developing new standards in the area of interoperability, authentication and data management, will have to consider the needs of all players, not just Big Pharma. That will force the agency to make some tough choices. For example, according to Mr. Fletcher, the larger pharma companies favor a distributed database, which each company controls, instead of a central data clearinghouse run by a third-party chosen by the FDA. “Small pharmacies at the end of the supply chain will likely not be able to support costly distributed systems, and will likely require faster authentication response times than larger wholesalers,” he said.

“Arguments are made against a centralized database because of the false notion that pharma transactions are too great,” he added. “If every one of the 4 billion prescriptions were shipped as individual units, and they were handled 10 times in the supply chain, the daily transactions would be much smaller than many other systems.”

Potentially complicating matters for the FDA is the fact that the European Union parliament approved a drug anti-counterfeiting program on February 15 to require member countries to design their own anti-counterfeiting systems during the next few years. These will probably require some kind of track and trace mechanism, but there is no guarantee that individual countries will adopt similar requirements, much less that those requirements will parallel any new standards issued by the GS1. Moreover, Axway’s Ms. Raley pointed out that European countries have different privacy concerns than the U.S., and regulate their information technology industries differently than the U.S. So the potential for different U.S. v. EU track and trace requirements certainly exists.

Despite the confusion and contention, Shabbir Dahod, chief executive officer and president of TraceLink Inc., developer of the TraceLink Network platform of supply collaboration and track and trace solutions for the pharmaceutical supply chain, called the workshop “a very productive meeting.” He explained that there were three key themes that seemed to emerge from the FDA event. First, that there was a consensus that the FDA must take a leadership role on track and trace. Second, that there was a desire to reduce the complexity and scope of track and trace implementation through a phasing in of requirements like California’s approach and adding in a layering of capabilities. “For example, maybe you start with serialization, then track and trace transactions, then implement full pedigree, add authentication and so on,” he stated. Finally, with regard to standards, Mr. Dahod said there is a drive towards “open standards” and that GS1 has made important strides in this area.

However, it is the manufacturers, not the wholesalers, pharmacies and hospitals, that have to take the first steps toward serialization, and they constituted the bulk of the attendees at the FDA workshop in February. The workshop may have stimulated some new interest among pharmaceutical companies in track and trace systems. For example, Bosch Packaging Services, Inc. held an open house at its Raleigh, NC manufacturing facility in late February. Sandro Gisler, manager, marketing and product development, stated there was a “good response” from the major pharmaceutical companies, many of which are already Bosch customers. Bosch has been doing a good business outside the U.S. in France, Turkey and Brazil where track and trace requirements are either already in force or shortly will be. “We are selling numerous machines outside the U.S. but everybody is kind of waiting on the FDA regulation,” he explained.

Stephen Barlas is a contributing writer for Contract Pharma. He can be reached at sbarlas@verizon.net.