Thinking globally for patient safety

As the US focuses on how to achieve an e-pedigree system and the European pharmaceutical industry moves toward a 2D datamatrix-based “bookend” system, there is a danger that patient safety will suffer from fragmented approaches and expensive implementation strategies. The time is right to take a global vision toward a harmonized approach to product surety that can provide achievable near term benefits to patient safety.

The increased globalization of the pharmaceutical trade means that getting drugs from the point of manufacture to the patients they are meant to help involves a supply chain that is growing more complex every day. Pharmaceutical industry participants including manufacturers, distributors, re-packagers and retailers may be located in different countries and even on different continents. Drugs frequently change hands multiple times before reaching the patients they are intended for. In addition, drug products are often repackaged by legitimate third party operations at which time original (primary and secondary) packaging may be discarded along with any countermeasure features and tracking information that may have been present. The complexity and weak controls over the pharmaceutical supply chain have made pharmaceutical products an attractive target for unauthorized distribution and counterfeiting.

Although there have been many proposed methods of safeguarding medicines, ranging from Paper Pedigrees, to radio frequency identification (RFID) and barcode based Electronic Pedigrees, the most effective path to patient protection is perhaps the simplest – a phased approach that initially focuses on the point of dispensing and bypasses the significant complexities and expense of a full supply chain pedigree system.

There are currently two major initiatives that are drawing most of the attention, and fragmenting the resources of the industry: the European Federation of Pharmaceutical Industries and Associations (EFPIA) initiative and the California ePedigree initiative. In addition, recent regulations in Turkey are now driving a third serialization initiative. The pharmaceutical industry has only recently emerged from several years of irrational exuberance surrounding the near-term potential of RFID technology. Let’s learn from that experience and choose a phased approach that leads to achievable near-term improvements in patient safety rather than seeking an all-encompassing solution that is focused on the supply chain rather than the primary focus, patient safety. In this regard, the EFPIA approach, which focuses on verification at point of dispensing, is more likely to provide near-term improvements to patient safety than is the California ePedigree initiative which requires full supply chain participation.

While the goals of the California ePedigree initiative may be lofty, they are too expansive to be achieved in the near term (next five years) and will dilute the resource and attention that could otherwise be directed toward providing near-term improvements to patient safety. We can learn from experiences over the past five years where resources and attention were disproportionately focused on trying to enable the supply chain with RFID technology. Although both ePedigree and RFID are likely to play important roles in the future, we should head there one step at a time, taking a path that provides improvements to patient safety at each step.

Now is the ideal time to build a harmonized and global approach to improved patient safety rather than head down divergent complex paths. Key organizations and agencies such as EFPIA, The European Medicines Agency (EMEA), the United States Food and Drug Administration (FDA), Pharmaceutical Research and Manufacturers of America, (PhRMA), the Japanese Pharmaceutical and Medical Device Agency (PMDA), and the World Health Organization need to align themselves towards a harmonized global approach that may be deployed in any region using currently available technologies. The International Committee for Harmonization (ICH), which was established to harmonize aspects of drug development between the US, Europe and Japan should also play a role in establishing a common foundation.

A global, harmonized approach to drug safety should be carried out with a central goal, verifying drugs at the most critical transaction in the drug’s supply chain – where drugs are dispensed to patients. This is essentially the “book-end” approach being developed by EFPIA. Although the cost and complexity of the “book-end” approach is significantly lower than the ePedigree approach, which follows product through the supply chain, it still requires two significant and challenging developments: 1) all products must be serialized at the unit level and 2) an industry wide data routing and data management system must be established.

Although both of these objectives are challenging and costly, they represent only a fraction of the cost and complexity of enabling a full supply chain pedigree system. Undertaking this initial step would enable near-term improvements to patient safety through point-of-dispensing verification, provide significant learning, and enable subsequent development of supply chain pedigree programs that can build on this foundation.

First, at the point of manufacture, drugs would be serialized with a unique item-level serial number,  printed on each individual unit of the drug in the form of a scannable 2D datamatrix code and a human readable alphanumeric. The item level serial code associated with the drug will reside in a manufacturer-controlled database. The use of a standardized, industry-wide data routing system, similar to those in use for banking and credit card transactions, will enable verification of information within each manufacturer’s data management system.

At the point of dispensing (eg. pharmacy, hospital, etc.), the item’s serial number would be scanned and the information routed to the manufacturer’s database for verification. The number would be checked against the serial codes in the database resulting an “approval“ or “denial” message or response sent back to the point of dispensing, as is the case in a banking or credit card transaction.

Multiple checks of the same serial number at the time of dispensing would raise a flag, triggering a “denial” for any future attempts to dispense. Questionable product would be set aside by the dispenser for further investigation, per agreed upon processes.

In addition to the points of dispensing, other potential inspection points such as corporate security, distribution centers, wholesaler sites, and returns centers may also be registered in the system. They will be recognized as non-dispensing points, where different business rules are established. These business rules may be used for reverse logistics procedures such as managing product recalls or simply managing product returns and credits processing.

Like bank ATM and credit cards, this system should allow for global use with universal results: either an “approval” or “denial” to dispense a drug product.

In developing countries that lack computer infrastructure, products may be checked by way of a cell phone text message. Cell phone verification would be highly advantageous for countries that have fragmented pharmaceutical distribution systems with poor regulatory and enforcement structures. While these developing markets may have challenges with a centralized computer infrastructure, their telecommunications systems or cell phone capabilities are reliable.

While serialization may be a part of an authentication program, it does not replace the need for authentication technologies. Overt and covert product authentication features applied by the manufacturer to both the product packaging and even the product itself, provide the manufacturer with rapid field detectable investigative capabilities. Furthermore, given the maturity of certain regions, the manufacturer may also wish to engage the consumer, providing public awareness campaigns, where the consumer may be asked to look for certain overt security features on the product. This may become part of the marketing branding strategies, where product surety is part of the manufacturer’s commitment to the patient.

To make this happen, the EFPIA, EMEA, FDA, PhRMA and WHO would need to team up and establish an industry standard with a data exchange infrastructure that would underpin the broad implementation of unit-level serialization. This collaborative approach is best achieved by using the “bookend approach”, which focuses on the manufacturing and dispensing ends of a given drug’s supply chain. This makes for a streamlined approach that may be implemented using existing 2D data matrix bar code technologies, existing barcode scanners and/or cell phone.

Over time, as emerging data carrier technologies are further developed (RFID, for example), this system may evolve as well. This harmonized global approach would effectively lay the foundation for the implementation of a more extensive track and trace system, which would track drugs as they move through their supply chain, providing the ultimate supply chain management tool.

While incidents of drug counterfeiting and unauthorized distribution continue to increase globally and risks to patients grow daily, all parties need to take a fresh view towards improving patient safety. This is a global issue that requires a harmonized global response and by focusing our resources on the point of dispensing we can achieve significant near term results while building a strong foundation to support future expansion to a full supply chain track and trace or pedigree system.