There is a good deal of talk in the pharmaceutical industry about serialization, and for good reason. Serialization combined with the system of track-and-trace constitutes the industries vigorous response to the growing problem of drug counterfeiting. Purposely producing and selling a drug that is intended to deceive, i.e. drug counterfeiting, is costing the industry tens of millions of dollars annually. Just as important, drug counterfeiting is a dangerous act and imperils the lives of those the industry works hardest to protect—the patients that must rely on safe and effective medications.

Easy to define, hard to combat
Drug counterfeiting is easy to define. Quite simply, it is a pharmaceutical product that is produced and sold with the deliberate intent of deceptively representing its origin, authenticity or effectiveness. It may contain incorrect quantities and qualities of active ingredients, or none at all. What is difficult to qualify or quantify, however, is the adverse effect drug counterfeiting has on global health and the cost to the global economy. Estimates of its impact on the industry range anywhere from $75-$200 billion and can make up nearly half of all drugs sold in some lower income nations. That means between eight and fifteen percent of all medicines sold worldwide could be fakes. In some sub-Saharan African countries, the proportion of counterfeits in the market is forecasted to be closer to fifty percent!

Looking through the prism of its impact on global health it is difficult to calculate, but simple to imagine the tens of thousands of lives that are adversely affected through this fraudulent act. Authorities worldwide are alarmed about the risk to individual health and disease control across populations as fake drugs often have substandard or incorrect formulations that can prolong illness, create resistance, or even result in death. Most counterfeit versions of drugs are known to be manufactured in the Asian region and distributed globally. However, even countries with strict surveillance and regulatory policies such as the U.S. and the European Union are not immune to the threat of counterfeits. What then, is the industry doing to control this problem?

Battling drug counterfeiters – an industry fights back
Regulatory agencies have been seeking and implementing new methods to thwart the counterfeiters and agree—relying primarily on clear means of verification and identification is the right action to take. Known in the industry as serialization and expected to be an effective solution by many countries, this system involves the assignment and application of a unique identification code to a product. With serialization, each saleable unit is assigned a unique identifier. Additionally, as an added precaution the pallets upon which the cases are packed are also assigned a unique identifier. The integrity of the packages is also protected with tamper indicators like pre-perforation, glue points or safety labels.
The term aggregation is used by the industry to define the relationship between multiple items within a product shipment such as cartons, cases and pallets. Together, serialization and aggregation form the foundation for track-and-trace, which documents a product’s current and past locations throughout the supply chain. The ability to track a product’s whereabouts and trace its path forms the core of a safer and more efficient drug supply chain.

Due to the importance of eliminating drug counterfeiting, many countries have already adopted regulations requiring the enactment of serialization. By 2019, the majority of the global drug supply will essentially fall under some form of serialization requirement. Countries that have already implemented this program include Turkey, India, Argentina, South Korea, and Saudi Arabia. China started the implementation of serialization by the end of 2015. However, they have placed a hold on their phased implementation of serialization regulation and the industry is still waiting for final guidance.

In the U.S., full implementation of serialization was originally required by November 2017 and all products sold into the country had to be serialized by this date. This ruling represents one of the most important rollouts of serialization regulations. However, newly released guidelines offer a one-year reprieve for manufacturers, which have not integrated product identifier requirements by the original deadline. This reprieve is also extended to trading partners who may wish to purchase products without a product identifier prior to November 2018. The one-year grace period is due to the potential disruption to supply chains and the concern that pharmaceutical companies and manufacturers are unprepared to meet the original deadline.

For manufacturers of pharmaceutical products there are several steps that must be followed and adhered to ensure compliance with the ruling. These steps include: the application of a Global Trade Item Number (GTIN) including the national drug code (NDC), a serial number, batch number, and an expiration date. Cases in which the product is contained must be printed with a linear barcode or 2D Data Matrix. Additionally, any requests from federal/state government organizations to verify serial numbers must be answered within 24-hours, and any data must be stored/archived for six years.

The European Union has also enacted a compliance deadline for EU member states—excluding the European Economic Area (EEA), and Switzerland—beginning February 2019. Belgium, Italy and Greece have an additional six years to comply. The requirements differ somewhat from the U.S., but also include serialization of the drug product at the smallest saleable unit. This includes the application of a unique product identification number (e.g. GTIN/NTIN/PPN), batch/lot number, expiration date, serial number, and if applicable, the national reimbursement number. As in the U.S., a Code Format 2D Data Matrix is required. These requirements are valid for all prescription drug products and certain over the counter (OTC) product drugs, which might be at risk of falsification (blacklist products). While requirements from the EU and the U.S. may differ on their approach to serialization, legislators and authorities of various countries are united towards one goal: achieving unique identification and clear verification of the authenticity of products.

As with any new system or regulations, there are usually impediments to adoption and implementation. With serialization, these include a tight schedule from the authorities that require the regulations. Additionally, pharmaceutical and biotechnology companies, as well as their manufacturers must always remain well informed about the current information as it pertains to timeliness, different country requirements and any changes that may arise. Contract development manufacturing organizations (CDMOs) with a packaging service have to be well prepared to result in a shortened timeframe for serialization projects. As such, the main challenges for manufacturers in managing such a project can vary, particularly if the drug product is supplied to several markets. A partner in the form of a CDMO that can offer flexible serialization solutions allowing for a rapid and efficient response to these variations may be one option for helping a pharma company achieve success in enacting serialization. But how does a company go about finding the right partner to help with serialization, and what attributes should they possess?

Choosing a CDMO: What to look for
The choice of the right partner to assist with serialization is crucial in ensuring that it is properly enacted. Because serialization requires a high-level of investment, it is essential that the CDMO be adequately invested in programs, technology and expertise. This is vital for the safety of the patient and the integrity of the product. Also important is the existence of a pipeline for investment in future-oriented techniques and approaches.

The CDMO should be able to demonstrate a long history of supporting customer and regulatory serialization demands. For example, having already implemented an IT solution to support serialization, lines to print and encode serialization data on packages, as well as the ability to manufacture products that are serialized according to the latest regulatory guidelines. Because implementation of a serialization service is a comprehensive project, a well-defined strategy and, preferably, one that begins with a concept study to start the project is essential. This means that the CDMO should have an established and solid cross-functional project team consisting of all the necessary departments including IT, engineering, production, supply chain, quality, regulatory affairs and project management. Each member of the team must have a strong working knowledge of serialization and be kept abreast of any new regulatory requirements. Due to the vital importance of serialization, some CDMOs have actually created the position of a Serialization Process Manager. This function is responsible for ensuring that all future requirements arising from different relevant markets and customers will be implemented successfully.

Drug counterfeiting cannot, and should not continue to hold the industry and the patients it serves as hostages. There are measures and steps that are currently being taken that are expected to help battle this growing problem. Time will tell how effective they will be. However, because existing programs like serialization can be costly, companies need to have the right resources and support to ensure they are undertaken correctly. That is why the choice of the right partner is vital. 

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Daniela Geiger holds a MBA in International Business Development from the ESB Business School Reutlingen, Germany. She started her career path in the pharmaceutical industry in 2003 contributing to different areas of the business in Latin America and Europe. Daniela joined Vetter in 2011. Currently she works as a product and service manager, responsible for the secondary packaging, serialization and sterile water for injection services.