Drug Packaging Serialization

A new FDA final guidance jump-starts track and trace

By Stephen Barlas

The FDA’s publication of the final guidance on a standard numerical identifier (SNI) for pharmaceutical packages at the end of March awoke the drug industry from its track and trace slumber. Manufacturers, distributors, pharmacies and their vendors had been snoozing since September 2008, when California pushed back its e-Pedigree implementation date, an action with significant national implications. Instead of having to put unique serial numbers on packages starting January 1, 2011, California, responding to pleas from an ill-prepared drug industry, pushed back that e-Pedigree deadline to January 1, 2015. One-half of all drug packages arriving in the state on that date will have to have unique serial numbers printed on them. The other half will have to follow suit one year later.

“Everybody took a deep breath when the California Board of Pharmacy delayed its e-Pedigree requirement,” agreed Ruby Raley, director, healthcare solutions, Axway, a company that provides the software to run the data repositories that hold information about drug package pedigrees as an individual package moves from the manufacturer to (perhaps) a repackager to a wholesaler and on to the retail or hospital pharmacy. Axway is involved in numerous track and trace pilots with a number of major pharma companies. “Nothing happened last year,” she remarked.

Now, publication of an FDA-approved package serialization scheme has given the pharmaceutical industry a reason to restart its version of California Here I Come. Whereas the California Board of Pharmacy provided no specifics on package serialization, the FDA has; manufacturers no longer have to wait and guess what might be acceptable in the Golden State come January 1, 2015, a date that, given the complexities of e-Pedigree compliance, isn’t so far away.

James McCrory, vice president, products and technology at rfXcel Corp., said, “The SNI guidance is a big deal in three ways. It reflects new interest in federal government safety of prescription drugs, provides endorsement of GS1, which is pretty big since people have been hanging back waiting to see what happens, and matches what leaders and distributors and manufacturers are doing in their own pilots.” The SNI essentially endorses the serialization standard adopted by the international standards group GS1. GS1 has one serialization standard for numbers printed in 2D barcodes (GT10) and a second one for numbers printed on radio frequency identification (RFID) tags (G10).

An agreed-upon format for an item-level SNI is only the first step in a closed-loop e-Pedigree (often used synonymously with track and trace) system such as the one adopted by California, and likely to be endorsed by Congress. Other follow-on elements include:

• security framework for data exchange,
• record retention policies,
• SNIs at the pallet and case level,
• standardized chain-of-custody data to be tracked by logistical units,
• standardized electronic data exchange format,
• data carriers with specific encoding formats identified,
• guidelines for reporting exceptions noted by supply chain participants, and
• hierarchy of the SNIs expected in a shipment.

The FDA SNI provides a first-step level of certainty to manufacturers, in terms of compliance with federal expectations, and assures them that the U.S. is moving in the same basic direction as other countries, many of whom are far more advanced in their national track and trace requirements. That is all true despite the limitations of the FDA guidance: it is a suggested package identification formula. There is no federal requirement that drug manufacturers follow it, much less put a serial number on each item-level package.

The limits of the FDA guidance, some of its nuances and its failure to address the important issue of which technology should be used to print the SNI have all combined, apparently, to seal the lips of pharmaceutical manufacturers who just three years ago were touting their track and trace efforts. Prominent proselytizers such as Pfizer, Abbott and Purdue Pharma have declined to comment on the FDA final guidance on an SNI. “I ran this request up the flag pole and have learned that we are unable to grant interviews on this topic,” explained Libby Holman, spokeswoman for Purdue Pharma, which has been an aggressive track and trace experimenter because of its manufacture of OxyContin, a popular target of drug diverters.

Tom McPhillips, vice president, U.S. Trade Group, Pfizer Inc., did not return an e-mail requesting comment. Mr. McPhillips, in his comments to the FDA after the draft guidance was published, asked the agency not to require manufacturers to print the national drug code (NDC) as part of both the machine readable and human readable SNI. The FDA rejected that request.

Nonetheless, manufacturers support the specificity of the SNI, and its agreement with GS1 standards, which gives them more certainty than California’s prescription for a unique serial number. The only guidance in the Golden State law, according to Virginia Herold, executive officer of the California Board of Pharmacy, is that the number be part of an “interoperable” track and trace system. The FDA-recommended SNI is a unique combination of two numbers printed on a package label that identifies the drug inside the package. The FDA final guidance specifies that half of the SNI is the national drug code (NDC), which is essentially unique for each drug made by each manufacturer, coupled with a unique serial number for the second half, generated by the manufacturer or repackager for each individual package. Serial numbers should be numeric or alphanumeric and should have no more than 20 characters. The SNI should be both machine and human readable.

The use of a GS1-compatible SNI means that manufacturers following the FDA guidance are very likely to comply with European, Brazilian, Norwegian and other national requirements for drug package serialization. Meanwhile, other countries are putting track and trace requirements into place, in some instances with more speed than the U.S. Ms. Raley explained that governments footing the bill for public healthcare (e.g. the EU, Brazil, Turkey) are especially concerned about counterfeit product sneaking into the country, since the government does not collect taxes on those transactions. “People are sneaking product in at the border, that is driving government concerns,” she explained.

In the U.S., the FDA has been more concerned about the prospective impact of counterfeit drugs on public health and safety. The 2007 Heparin recall underlined the value of track and trace (had it been deployed by the pharmaceutical chain) with regard to drug recalls. Preventing thefts is an important affiliate benefit, too. In March, thieves broke into an Eli Lilly warehouse in Enfield, CT and stole $75 million worth of prescription drugs. The crooks took pallets of the anti-cancer drugs Gemzar and Alimta, the schizophrenia drug Zyprexa, the antidepressant Cymbalta and other prescription medicines. Theoretically, those stolen drugs could not come back into the legal distribution chain if they had SNIs printed on 2D barcodes or RFID tags on each package’s label.

It is clear that manufacturers are the big winners, relatively speaking, from the final guidance. Scott Melville, senior vice president for government affairs for the Healthcare Distribution Management Association (HDMA), said, “The FDA guidance provides manufacturers and the entire pharmaceutical supply chain with needed clarity.” But while the HDMA has welcomed the guidance, it clearly did not get everything it wanted. For example, the HDMA had not wanted the FDA to endorse an “alphanumeric” as a serial number option.

However, Anita Ducca, senior director, regulatory affairs at HDMA, acknowledged the FDA was responsive to her group’s concerns. “We had a number of things we wanted the FDA to change from its draft guidance and for the most part the agency did that,” she states. “Our members are ready and willing to work within the parameters of the guidance.”

Neither did hospitals and pharmacies get exactly what they wanted. Some pharmacy groups had also pushed for a different SNI. The American Society of Health System Pharmacists (ASHP) had urged the FDA to modify the NDC number so that its components included the RxNorm CUI as the drug/form/ dose component of the code. Justine Coffey, JD, LLM, director, federal regulatory affairs, said, “Currently, ASHP members are struggling with inconsistencies relating to the National Drug Code (NDC) and its application to barcode point-of-care, clinical information systems, and hospital financial systems.”

Axway’s Ms. Raley noted that hospitals are particularly concerned about avoiding medication errors, especially given the passage of the health care reform bill, which mandates a number of new payment methodologies based on the hospital reducing errors of all kinds. She explained that many drugs come in many formulations and doses, information which will not be gleaned from the SNI endorsed by the FDA. Ms. Raley pointed out that hospitals are particularly sensitive to this issue given the publicity generated by the misadministration of Heparin to twins born in November 2007 to the actor Dennis Quaid and his wife.

Minor reservations aside, the HDMA’s Mr. Melville emphasized that the final guidance allows his members and everyone else to move forward. “The first step in an e-Pedigree system is putting a number on the package,” he said. “The second step is what you do with that number.”

For distributors a big issue is how the SNI is printed on the item-level package label. The two options that have emerged over the past half-decade are a 2D barcode or a radio frequency identification (RFID) tag. Distributors have generally favored RFID tagging, since they could check in packages to their warehouses without a reader having to be “in the line of sight” with the individual package. This saves them time, which is important because any e-Pedigree requirement costs the distributor money and earns the company no profit. But RFID tags are expensive, and manufacturers have generally pushed for printing serial numbers within 2D barcodes, not just because the labels are cheaper, but because the packaging lines can run faster than they could if RFID tags are printed on the package. Moreover, RFID tags cannot be used on some products.

The final guidance on the SNI appears, however, to endorse 2D barcode serialization without actually saying so. “The FDA landed on 2D,” stated Ms. Raley. “It is very clear they talked about the total acceptability of 2D although they did not rule out RFID.” RFID does have some significant shortcomings when it comes to package use, such as its deleterious effect on biologics.

Robert Celeste, director, healthcare, GS1 US, said that in fact all the manufacturers who have done pilots, and are doing them now, are putting serial numbers on packages via 2D barcodes. Some are also putting RFID tags on the product label, and on cartons and pallets. He believes it is possible that RFID tags on item-level packages may have utility — if their per unit price comes down — in certain applications, for example, where products must be kept at certain temperatures.

The final guidance, however, is silent on serialization of cartons and pallets, which the California Board of Pharmacy, just to cite one interested party, had pushed for, and on which the FDA had asked for comments.

While the pharmaceutical supply chain now knows that the SNI is the baseline for complying with California’s e-Pedigree requirement, everyone up and down the chain is pushing for federal legislation that would make the California requirement, or some close version of it, national law and might resolve outstanding technology questions as well. The 2007 congressional law that required the FDA to publish some sort of SNI within 30 months — it did not specify guidance versus more legal regulation — also told the FDA to “develop standards and identify and validate effective technologies for the purpose of securing the drug supply chain against counterfeit, diverted, subpotent, substandard, adulterated, misbranded, or expired drugs.” The FDA received comments but has done nothing to impose a technology solution, which various players in the drug distribution chain would probably oppose, but which is clearly necessary.

In the 2007-2008 session of Congress, Reps. Steve Buyer (R-IN) and Jim Matheson (D-UT) introduced the Safeguarding America’s Pharmaceuticals Act, which would have established a federal e-Pedigree mandate. That law has not been reintroduced in the current Congress, perhaps, suggested Ms. Herold of California’s Board of Pharmacy, because members of the House and Senate have been overwhelmed with healthcare reform, financial reform and economic recovery. Also, the same sense of urgency that disappeared in California in September 2008 disappeared from Congress at about the same time.

As the HDMA’s Mr. Melville put it, “We want a uniform federal pedigree standard. We can’t have barriers to movement of products.” He added that Reps. Buyer and Matheson, at a hearing on March 10, stated they are working on a redrafted version of their bill. “We are very hopeful it will be reintroduced soon,” said Mr. Melville. “We expect it to look like the California implementation schedule.”

Stephen Barlas is a freelance writer who has written several articles on pharmaceutical packaging for Contract Pharma. He can be reached at sbarlas@verizon.net.