FDA Guidances Offer Oversight Clues to Industry

As FDA sorts out draft guidance comments on serialized National Drug Codes and Physical-Chemical Identifiers, the agency is also working on several investigations into several stolen drug products.

Thousands of drug products have been stolen this year alone. Novo Nordisk products stolen in North Carolina have resurfaced at a Houston medical center. The company reports that three lots of 10-ml vials of Levemir (insulin detemir [rDNA origin] injection) were stolen and later located in Houston. "Insulin from these lots did not circulate through the normal Novo Nordisk distribution channel and therefore proper storage conditions for the insulin may not have been followed," it reports. http://press.novonordisk-us.com/index.php?s=43&item=204

Astellas Pharma U.S. reported in June that a tractor-trailer carrying several parenteral drug products was stolen and remains missing. Drugs packaged in prefilled syringes, vials, ampules, blister packages, and tubes were on the trailer. Affected lot codes were released to healthcare professionals and patients. www.astellas.com

The Partnership for Safe Medicines reported that another tractor-trailer truck containing a 35,760-carton shipment of Dey brand generic Albuterol Sulfate Inhalation Solution was stolen in McKinney, TX, in August. Again, affected lot numbers have been released. http://www.safemedicines.org/2009/08/asthma-drug-theft-alert-and-public-warning.html

Each carton displays the brand name "DEY" and contains 30, 3ml single-dose vials of solution. The lot numbers of the stolen products are 9G01 and 9FE2.

FDA's Counterfeit Drug Task Force hasn't met in a while, but the agency did mention in its Transparency Blog its Sentinel program for improving the tracking of pharmaceuticals and medical devices to ensure patient safety. On the surface the program appears to focus on eased adverse-event reporting and the potential role of electronic medical records.

But through item-level serialization of drugs and devices, the agency could help the healthcare industry piece it all together—product verification, safety, recalls, reimbursement.

When asked about item-serialization and recalls, FDA's Ilisa Bernstein said that "item-level serialization could be a useful tool to target recall of specific items. Currently we are working on a guidance to develop standards for a standardized numerical identifier (SNI) to facilitate item-level serialization."

Your company is most likely awaiting final word from FDA on SNI standards, mandated for release by March 2010. The agency is also expected to issue its plans for UDI any day.

But it is never too early for you to begin providing the tools to enable FDA, the Department of Justice, and other law enforcement agencies to better investigate drug theft, diversion, and counterfeiting. Judging from the few cases mentioned above, investigators have their hands full. Item-level coding could be the evidence needed for complete track and trace and prosecution.

Awaiting Final Thinking on the SNI

The Next Important Deadline after Tax Day

Fed Invests in Electronic Records

Given the volatility in the U.S. economy, preparing for far-off serialization and electronic pedigree rules may seem like a luxury your company cannot currently afford. With years to prepare for California laws and federal standards still taking shape, you may be tempted to postpone any investments in technology or partnerships.

Aside from specific laws or standards on unique identifiers, other federal activity may push your company toward better product identification using automatic means. In fact, economic developments themselves may encourage you to step forward with product identification strategies. Earlier this week, President Barack Obama signed the American Recovery and Reinvestment Act of 2009 (ARRA) into law. Among the president's economic priorities is "making the immediate investments necessary to ensure that within five years, all of America's medical records are computerized." The act potentially allocates up to $2 billion toward building the needed infrastructure.

Why could such investments encourage product serialization sooner than mandated? Wiring the healthcare records system will involve many players, from physician offices to hospitals to pharmacies. And with Medicare offering economic incentives to doctors for e-prescribing, healthcare professionals are motivated now more than ever to utilize electronic systems.

Electronic records are not without their controversy, given patient privacy concerns and fears of too much government oversight. But if you consider President Obama's stated objective for electronic records—to reduce medical errors and reduce costs—the healthcare system needs better patient and product identification.

Why then would the electronic revolution stop at your products? It may not be today, or even next year, but there will come a time at which hospitals and pharmacies and insurance companies will no longer want the expense or liability of manually identifying and recording the use of pharmaceuticals or medical devices. Automatic identification of products will be relied upon to speed recalls, ensure patient identification and proper drug or medical device administration, verify product authenticity and custody, and so on.

It may take years to flip the switch, so to speak, but it also may take your company years to add unique identifiers to your packaging. For now, the only firm timeline industry can follow is that FDA has until March 2010 to develop standards for unique identifiers for drugs; there is no mandate for FDA for unique medical device identification. Last week FDA held a workshop on Unique Device Identification for medical devices. While such standards are still under development, Jay Crowley of FDA's Center for Devices and Radiological Health explained that FDA is looking at the use of a two-part identification system--one code would be the medical device identifier, while a second companion code would be a production identifier. That second code would be the lot number (for identifying a given group of devices) or a serial number (for identifying individual devices); it would also contain the expiration date if the label carries one.

"We are not trying to recreate the NDC [National Drug Code] but perhaps come up with an equivalent," said Crowley . For medical devices, "we need a common understanding and a common visibility. [For instance] there are a lot of device recalls, and we need to be able to do them better--efficiently and effectively."

Regarding drug identification, FDA's Ilisa Bernstein spoke briefly about the recent draft guidance, calling it "closely related." The proposed serialized NDC would include a unique 8-digit serial number, she explained, and it would be compatible with the serialized Global Trade Item Number (sGTIN).

Bernstein's presence at the workshop was telling in and of itself. FDA seems to be looking at product identification across agency centers in ways that could help each learn from the other. But given the varying risks posed by drugs and medical devices, different rules (or standards) may emerge. For instance, given Crowley 's comments and others at the UDI workshop, the driver for devices is to improve identification of recalled lots, and therefore lot-based coding seems to be in favor. For drugs, however, given counterfeiting and diversion risks (for details see the State story), serial numbers are being looked at to improve item visibility.

However the details unfold, pharmaceutical and medical device packagers need to start looking at adding a variable coding component to their labeling. The rules (or standards) may take a while to solidify, and you may even have a voice in their development.

At some point, however, you will need to support the coming electronic revolution in healthcare with more prevalent and complete automatic identification. Not only will you need to facilitate the automatic identification of your products, but perhaps also their lot and serial numbers.

Do Not Delay, Says FDA

FDA believes that serialization using unique identifiers and a “good” electronic track-and-trace system can help secure the pharmaceutical supply chain. In an interview with Pharmaceutical & Medical Packaging News, Jeffrey Shuren, M.D., J.D., FDA’s associate commissioner for policy and planning, explained that while FDA believes drug track and trace and authentication are two “somewhat separate functions,” both could be accomplished with one system. “Optimally, that is where we will end up—with an electronic track-and-trace system,” he said.

FDA is mandated under the FDA Amendments Act of 2007 (FDAAA) to develop or adopt a “standardized numerical identifier” by March 2010. According to FDAAA, “this standardized numerical identifier is to be applied to a prescription drug at the point of manufacturing and repackaging (in which case the numerical identifier shall be linked to the numerical identifier applied at the point of manufacturing) at the package or pallet level, sufficient to facilitate the identification, validation, authentication, and tracking and tracing of the prescription drug.” FDA plans to seek public comment on a proposed standard in time to adopt and issue a final standard on unique identifiers by March 2010. There is no deadline for standards for a track-and-trace system, says Shuren, but he emphasizes that adopting or developing such standards is a high priority for the agency.

The delay in California’s electronic pedigree deadline until 2015 “highlights the importance of a federal solution,” says Shuren. “At this point, however, it is too early to say whether we will mandate the use of unique identifiers or whether our standards will be announced through guidance.”

Risk-based implementation of a unique identifier makes the most sense, Shuren says. However, FDA does not believe that the use of track and trace should be limited to just high-risk products. During his presentation at the RFID Track and Trace Healthcare Summit 2008 on November 17, for instance, Shuren pointed to the risks posed by counterfeit toothpaste.

FDA is also considering extending tracking standards to cover drug ingredients.

“It is important to know the source of ingredients, because they can come from around the world,” says Shuren. He adds that a good electronic track-and-trace system may have helped in the investigation of contaminated Heparin.

FDA is also looking at similar standards for pharmaceuticals and medical devices. “Our experience in pharma will inform our options for medical devices. Although we have a statutory deadline for adopting unique identifier standards for drugs whereas we do not have a statutory deadline for any other activities for drugs or devices, these other activities are agency priorities.”

This month, FDA will extend the expiration date of its RFID Compliance Policy Guide (CPG) 400.210. “Research on the use of RFID needs to continue, so we need to extend the CPG,” Shuren says. “However, the CPG on implementation of the pedigree rule has expired. There is no need to revisit the CPG at the current time in light of ongoing litigation concerning the rule.”

Shuren says that manufacturers should not delay their track-and-trace efforts until FDA issues guidance or rules. “Manufacturers should not wait to explore what their particular technological and operational needs will be for the tracking and tracing of their products. They should be assessing how to tailor technologies to their production processes now.”

FDA is still busy drafting standards for unique identifiers, for both drugs and medical devices. Work is well under way on unique device identification (UDI), which could very well guide the agency's policies on drug identification.

Making identification standards all the more urgent are two breaking news stories: more counterfeiting cases and more melamine troubles. In August, more than a dozen potentially counterfeit drugs were discovered at two Baltimore branches of The Medicine Shoppe. FDA reports that the products "were either expired or suspected counterfeit." (FDA continues to investigate, but the agency nor The Medicine Shoppe would comment on how or why these products were suspected.)

And in September, news broke of more melamine-contaminated products from China . Infant formula manufactured in China had been made with melamine, reportedly to boost protein levels for quality testing. No U.S. consumers or companies appear to be at risk, FDA reports. "FDA had contacted the companies who manufacture infant formula for distribution in the United States and received, from the companies, information that they are not importing formula or sourcing milk-based materials from China," the agency's site reads. Melamine was also found in a few other milk-containing foods, specifically tea and candy, and FDA is continuing to scrutinize other milk-containing products coming out of Asia.

Could item serialization have helped identify these cases sooner? Perhaps. Because FDA and The Medicine Shoppe remain quiet on how the potentially adulterated drugs were discovered, it is difficult to say whether serialized drug identification could have alerted pharmacists or patients much earlier. The bigger questions, though, are how did a dozen-plus potentially counterfeit drugs get through the drug supply chain to a chain drug store? And how many more counterfeits are left undetected?

With melamine being used to mimic protein, the problem is a little different. The companies themselves appear to play some role in the contamination, not counterfeiters. It brings to mind this year's heparin contamination with oversulfated chondroitin sulfate as well as last year's pet food contamination with melamine.

If similar cases were to occur in the pharmaceutical industry, unique item identification could be used to identify suspect products faster. Such visibility could reassure consumers and practitioners that legitimate medicines are safe. Pharmacies and other retailers may be able to conduct limited recalls, if necessary, leaving legitimate products on shelves.

U.S. patients and consumers are becoming increasingly aware of contamination and counterfeiting threats. Preserving patient confidence is critical. Unique item identification will enable supply-chain partners and authorities to track legitimate products and isolate suspect ones.

FDA Aims to Define a Standard Product ID by 2010.