From Serialization to Aggregation: A Holistic Approach

Counterfeit drug products and their potentially fatal outcomes are in the news nearly every week. The market for counterfeit versions of drug products such as potency l pills and heparin is booming and can have higher profit margins than the cocaine trade. For consumers, it’s often nearly impossible to detect whether a product is genuine or counterfeit. Numerous laws and guidelines have already been enacted or will soon come into effect around the world to protect consumers from these threats.

As a result, pharmaceutical manufacturers and contract packagers are faced with the challenge of selecting the appropriate technologies to meet these laws’ requirements and integrating those technologies into their existing production and packaging processes. In this article, I’ll discuss the requirements of these drug safety laws and explain why the safest option for meeting these requirements is to adopt a holistic approach consisting of a scalable machine-and-software concept. 

The Drug Supply Chain Security Act 

On November 27, 2013, the US adopted the Drug Quality and Security Act (DQSA). Title II of the DQSA, the Drug Supply Chain Security Act (DSCSA), outlines the steps pharmaceutical companies must take to implement a serialization system that identifies and tracks drug products distributed in the US. In early 2015, implementation began on the batch level. The law required mandatory serialization of primary packaging by November 2017. While the DSCSA has remained unchanged, in 2017 the FDA announced that it would delay penalties for noncompliance with the law until November 2018 to give pharmaceutical companies more time for implementation. 

As the FDA’s enforcement delay indicates, meeting the DSCSA’s serialization requirements has been challenging for many pharmaceutical companies. The biggest challenge, however, will come in 2019, when pharmaceutical wholesalers must also know the serial number—either in the form of the National Drug Code (NDC) or the Global Trade Identification Number (GTIN)—of each individual package and outer packaging. 

By the end of November 2023—exactly ten years after commencement of the DQSA—the complete connection and aggregation of the drug product supply chain will be implemented. 

Anti-Counterfeiting Efforts Around the World 

The European Union’s Falsified Medicines Directive 2011/62/EU, which came into effect in February 2016, requires pharmaceutical companies to use coded packaging with unique serial numbers for all prescription drug products starting February 9, 2019. As in many other countries, the serialization requirement is a 2D data matrix code (Photo 1) that contains a randomized serial number, the batch number, and the expiration date, as well as other data, as required. At the same time, the EU demands a second level of security in the form of a tamper-evident closure such as an integrity seal or glue, as described in the European standard EN 16679:2015-03, to clearly indicate whether a package has been previously opened or tampered with. 

Many other countries are developing and implementing serialization laws as well. In the Middle East and Northern African (MENA) region, efforts to ensure drug traceability are already underway. Saudi Arabia, for instance, initiated the first phase in March 2015, with obligatory data matrix codes on pharmaceutical packaging. Phase two—actual serialization—came into effect in 2017. While phase one only required a machine to print data matrix codes, phase two required producers and packers to have machines for serialization as well as an IT infrastructure to generate the serial numbers. Russia and other Eastern European and Eurasian countries will be introducing similar regulations and laws within the next few years. 

These various national and regional anti-counterfeiting laws all have the same purpose, but they contain some fundamental differences that impact the requirements for both local pharmaceutical companies and importers. The EU, for instance, assigns special importance to tamper-evident seals, while other regions such as the US focus on aggregation very early in the implementation process. While these serialization laws might be seen as regional, they all have a global impact. Large pharmaceutical companies often operate manufacturing facilities in many different countries and export their products all around the world. For these companies, it would be very short-sighted to equip packaging lines to meet the requirements of just a single local standard. 

For example, if a large generic producer from the MENA region sells its products not only in the local market but also in Europe and the US, its packaging must conform to several different serialization standards despite the fact that most of the products are packaged regionally. The same applies to contract packaging organizations, who must comply with their clients’ requirements along with the requirements in each of their clients’ markets. 

Meeting Global Requirements 

Because of these varying local standards, manufacturing and packaging companies will need to develop and apply a global strategy for generating and assigning serial numbers that’s compatible with multiple in-house processes. Companies must also establish processes to manage and store these serial numbers. To meet these needs, a serialization and aggregation solution must be highly flexible and modular. It must be able to mass-serialize the packaged product, verify the codes, and apply labels or tamper-evident seals to the packaging. Also, the software controlling the entire process must be easily integrated into existing IT infrastructures and the data must be retrievable at any time, providing producers and dispensing points an exact overview of all the steps in the manufacturing process.

A Holistic Approach to Serialization and Aggregation 

A holistic approach to serialization and aggregation can be divided into four levels, as shown in Figure 1. The serialization process starts on the application (or station) level (Level 1), where serial numbers are printed onto folded cartons, a camera system automatically verifies the printed tracking data, and a tamper-evident security seal is applied to the carton. However, serialization isn’t limited to folded cartons. A holistic serialization solution should be able to print and verify labels on bottles as well (Photo 2) along with the option of a so-called helper code that can be applied to the bottle’s bottom or cap, if required. In addition to serializing the smallest sealable unit (the carton or bottle), a holistic solution will include modules for the aggregation of products at different packaging levels, such as bundles, cases, or pallets. 

All Level 1 serialization modules should be controllable via a central user interface, with the ability to document the data (Level 2). To control both the operating conditions and data at any time, the connection between the physical machine level and the control software must be integrated across many stages of the company’s IT (Level 3). From this level onwards, the solution’s track and trace software must ensure that all the company’s production sites are depicted. Connecting the data between all production lines makes it possible to monitor the entire production environment from one central location, even if the lines are situated at different plants (Level 4). All relevant data is available in the entire company network, and all results are recorded in the audit trail. The data sets are bundled with the production results according to aggregation specifications and sent back to the track and trace software. From there, they can be transferred to manufacturer and/or government databases. 

Depending on country and guideline, serial numbers are either allocated centrally or generated by the company. Contract manufacturers in turn receive the numbers from their clients. A holistic serialization solution should be equipped for all cases. Companies should not only be able to manage serialization from serial number allocation through the last aggregation step, they should also be able to flexibly connect single components, third-party machines, packaging lines, their own or third-party IT systems, and entire factories with each other according to the applicable guidelines. It really is worthwhile for manufacturers and contract packagers as well as mechanical engineering companies with a focus on international customers to look at the big picture and take a holistic approach to serialization and aggregation.