Pharmaceutical serialization: How drug traceability works

Counterfeit medicines are a real threat to patients—even in Europe. To effectively protect the legal supply chain, the EU has made serialization mandatory for almost all prescription medicines subject to verification since February 2019. But how does this system work in practice? This guide explains in plain language which codes belong on medicine packaging, how data transmission works, and which technical standards are relevant.

Why serialization is essential in the pharmaceutical industry

The World Health Organization (WHO) estimates that in low- and middle-income countries, around ten percent of all medicines are counterfeit or substandard. However, there have also been isolated cases in the EU where counterfeit medicines have entered the legal distribution channel—a form of product piracy that endangers patient health. The consequences can be devastating: ineffective therapies, dangerous ingredients, or even serious damage to health.

The EU Falsified Medicines Directive (FMD) has created a comprehensive safety system. It is based on Directive 2011/62/EU in conjunction with Delegated Regulation 2016/161. The regulations have been in force since February 9, 2019: Almost all prescription medicines in the EU must be provided with unique safety features. This system of pharmaceutical serialization enables uniform verification of the authenticity of each individual package throughout Europe immediately before it is dispensed to the patient and significantly improves traceability in the supply chain.

Practical check:

Is your line already EMVS-ready?

Download free checklist

The two safety features according to FMD

The EU Falsified Medicines Directive stipulates two mandatory safety features that must be affixed to every medicine package as a distinguishing feature:

1) Unique identification code

The first safety feature is the unique identification code, also known as the individual serial number. This machine-readable code is printed on the packaging as a 2D DataMatrix barcode and contains several data elements. Each package is assigned a randomized, unique serial number with up to 20 alphanumeric characters, which must remain unique for at least one year from the expiry date or at least five years from the date of placing on the market.

2) Anti-tampering device

The second security feature is a device to prevent tampering, known as an anti-tampering device or first-opening protection. This must be affixed to the packaging in such a way that any unauthorized opening is detectable. This ensures that medicines have not been tampered with on their way to the patient—an important aspect of counterfeit security.

The 2D DataMatrix code: the heart of serialization

The machine-readable DataMatrix code is based on the ISO/IEC 16022 standard and uses ECC200 error correction. This makes the code particularly robust and reliably readable – even with poor print quality or damage. Unlike conventional barcodes, 2D codes can store significantly more information in a very small space.

The DataMatrix code appears as a square or rectangular pattern of black and white modules. Typical sizes are 26x26 or 26x40 modules, although smaller formats are possible as long as all the necessary data can be encoded. The code is printed directly onto the outer packaging by the manufacturer and contains four mandatory data elements:

Product code

The product code uniquely identifies the medicinal product. There are country-specific differences here: In Germany, this can be represented either as an NTIN (National Trade Item Number) or a PPN (Pharmacy Product Number), both formats containing the eight-digit Pharmazentralnummer (PZN). Alternatively, the 14-digit GTIN (Global Trade Item Number) according to the GS1 standard is often used internationally. The data identifier for the product code in the DataMatrix is “01”.

Serial number

The serial number makes each individual package unique. It is randomly generated by the manufacturer and must not be repeated within the specified time periods. In the DataMatrix, it is encoded with the data identifier “21”.

Batch number (LOT)

The batch number allows assignment to the production batch and is encoded with the data identifier “10”. It can contain up to 20 alphanumeric characters.

Expiration date

The expiration date (also known as the expiry date) is represented in the format YYMMDD (year, month, day) with six digits and is assigned the data identifier “17”.

A fifth data element can be added optionally: the national reimbursement number. In some EU countries, its inclusion in the code is mandatory. All four (or five) data elements must be printed on the packaging in human-readable plain text in addition to the machine-readable code.

Marking with DataMatrix codes requires precise printing technology and reliable quality control. Discover our serialization solutions for the pharmaceutical industry, which can be seamlessly integrated into existing production lines and support 21 CFR Part 11-compliant operation.

GTIN, NTIN, and PPN: Product codes at a glance

The various product code formats may seem confusing at first, but they all serve the same purpose: to uniquely identify the medicinal product.

The GTIN is an internationally standardized format according to GS1, consisting of 14 digits. It is composed of a country code, the company number, the item number, and a check digit. The GTIN is used worldwide in the pharmaceutical and other industries and enables cross-border compatibility.

The NTIN was developed specifically for the healthcare market and is a 13-digit number. In Germany, it consists of a special prefix for drugs (4150), the eight-digit PZN, and a check digit (13 digits in total). For use in DataMatrix or as GTIN-14, it is extended to 14 digits by adding a leading 0. This format takes into account the special features of the German billing system, in which the PZN plays a central role between pharmacies and statutory health insurance companies.

The PPN (Pharmacy Product Number) is a standard developed by the IFA (Information Center for Pharmaceutical Specialties). The PPN also encodes the PZN, but according to a different scheme than the NTIN. Pharmaceutical manufacturers in Germany are free to choose between PPN and NTIN – for pharmacies, it is irrelevant which standard is used, as both formats can be processed by scanners without any problems.

How the European Medicines Verification System (EMVS) works

At the heart of European pharmaceutical serialization is the EMVS—a unique, multi-level database and retrieval system. It consists of two main components:

European Hub

The European Hub is operated by the European Medicines Verification Organisation (EMVO) and forms the central database system. Pharmaceutical manufacturers and parallel importers upload their serialisation data to this hub via secure connections. The hub acts as a docking point and distributor, forwarding the data to the relevant national systems.

National verification systems

The national verification systems are operated by the respective National Medicines Verification Organizations (NMVO) in each EU member state. In Germany, this is securPharm, and in Austria, it is the Austrian Medicines Verification System (AMVS). These national systems operate the data repositories that pharmacies, wholesalers, and hospitals access for authenticity checks and verification.

The data flow in detail

The data flow takes place in several steps: First, during production, the pharmaceutical manufacturer creates a unique serial number for each package and prints the DataMatrix code on the packaging. Before the product leaves the production facility, the product master data and serialized package data are uploaded via the European Hub. From there, they are automatically forwarded to the national data repositories of the countries where the product is to be distributed.

During the distribution phase in retail, wholesalers can carry out risk-based spot checks and verify the authenticity of packages—for example, in the case of returns or parallel imports. Final verification then takes place at the pharmacy or hospital immediately before dispensing to the patient. The scanned code is checked against the national data repository in real time. If the data matches and the serial number has not yet been checked out, the product is released. The serial number is then deactivated in the system so that it cannot be reused.

Technical check for your line

Check in 5 minutes whether printing, verification, and

data connection are compliant with standards.

Download Checklist

Practical example: Verification in German pharmacies

In Germany, serialization is implemented via the securPharm system. This was developed jointly by the pharmaceutical industry, wholesalers, and pharmacists' associations and was successfully tested even before the official EU launch.

When a patient picks up a prescription medication from their doctor at a pharmacy, the pharmacy staff scans the DataMatrix code on the packaging. The pharmacy system sends an anonymized message with the verification request via the German Pharmacists' Network (NGDA) to the central database of the pharmaceutical industry, which is operated in Germany by ACS PharmaProtect. The identity of the pharmacy remains protected by pseudonymization.

Within milliseconds, the system checks whether the serial number is valid, whether it matches the specified PZN, batch, and expiration date, and whether it has already been checked out. If the result is positive, the pharmacy receives the “green light” – the package is dispensed to the patient and simultaneously deactivated in the system. If, on the other hand, a warning message appears – for example, because the serial number has already been used, is not in the system, or has been reported stolen – the package may not be dispensed. In the event of discrepancies, the incident is investigated to distinguish between handling errors and actual counterfeits.

Practical experience shows that the system works reliably. In 2020, over 1.3 billion packages of medicines were dispensed in Germany; in the same year, the German Pharmacists' Medicines Commission (AMK) reported only 10 suspected cases of counterfeiting in the legal supply chain. More than six million scans are performed every day – once the serialization requirements have been fully implemented, this figure is expected to rise to ten million scans per working day.

Special challenges: Export, import, and returns

Serialization poses special challenges when medicines cross EU borders or flow back within the supply chain.

When exporting to non-EU countries, packages must be checked out of the system – the key question here is the right timing. Depending on the country, decommissioning takes place when the goods leave the warehouse or when they arrive at the export partner's premises. Companies need flexible serialization solutions that can automatically implement these different requirements.

In the case of parallel imports within the EU, parallel importers assume the role of pharmaceutical manufacturers. They generate their own security features and upload them to the EMVS. The original serial numbers must be decommissioned and replaced with new ones.

Returns from pharmacies or wholesalers pose another challenge. Packages that have already been checked out can be set to “active” again within a ten-day period, as long as they have not left the control area. Damaged packages, on the other hand—for example, if the tamper-evident seal is compromised—must be decommissioned immediately and permanently.

Added value beyond counterfeit protection

Serialization of pharmaceuticals not only offers security benefits, but also optimizes operational processes. Pharmacies benefit from the fact that batch numbers and expiration dates are machine-readable and can be automatically transferred to the merchandise management system together with the PZN (German pharmaceutical product number). This reduces manual entry errors and speeds up goods receipt—a real added value in daily use.

In the event of product recalls, the system enables the precise identification of affected batches. Instead of blanket recalls, individual serial numbers can be traced in a targeted manner. This minimizes economic damage and significantly increases patient safety.

For pharmaceutical manufacturers and wholesalers, the complete documentation provides valuable data for optimizing the supply chain. Throughput times, inventory levels, and distribution channels become more transparent. This track-and-trace potential will be even more widely used in the future when EU legislation is developed beyond mere verification.

Integration into existing production lines

The technical implementation of serialization requires careful planning, especially when space is limited in production and packaging lines. Manufacturers need systems that generate serial numbers, print DataMatrix codes, check print quality, and automatically transmit the data to the EMVS.

Modern serialization solutions and serialization software solutions are compact and can be integrated into minimal space. They typically include a code printer, camera systems for checking print quality, labeling stations for tamper-evident seals, and the necessary software for data management and transmission. These systems communicate with national and European databases via API interfaces.

For smaller batches or production series, specialized packaging service providers offer the option of delivering folding cartons and labels already printed with all the necessary serialization codes. This makes serialization economically feasible even for medium-sized pharmaceutical manufacturers. In addition, modern technologies enable aggregation—i.e., the linking of individual packages into shipping units—which further increases efficiency in logistics.

Are you planning to integrate serialization systems into your production? Let us work together to develop the optimal solution – compact, efficient, and fully EMVS-compliant. Our modular complete solutions consist of serialization, labeling, and aggregation – all from a single source.

Outlook: Harmonization and further development

The EMVS now covers all EU and EEA countries; Switzerland is also connected via its own national verification system. Italy and Greece were granted extended transition periods for implementing the EU requirements; Italy is currently still in a national transition phase until 2027, during which the existing Bollino system will be merged with FMD-compliant serialization.

The first few years have shown that the system works in principle, but there is also room for improvement. The quality of the uploaded data is crucial – incorrect or incomplete data records lead to false alarms, which burden workflows. Cooperation between the national systems and the European Hub is being continuously improved in order to increase system performance and minimize problems.

In the long term, serialization could be expanded beyond pure counterfeit protection. Industry experts see potential for comprehensive track-and-trace systems that not only verify authenticity but also document every change of station in the supply chain. This would create even more transparency and form the basis for data-driven optimizations in the pharmaceutical supply chain. Above all, this could offer additional security for customers and patients.

Conclusion: Serialization as a successful model for patient safety

Pharmaceutical serialization in accordance with the EU Falsified Medicines Directive is an ambitious but successful project. With the 2D DataMatrix code, the unique serial number, and the Europe-wide EMVS verification system, a technical infrastructure has been created that reliably keeps counterfeit medicines out of the legal supply chain and protects the market in Europe.

Implementation in practice is running smoothly: millions of scans every day in pharmacies and hospitals confirm the authenticity of medicines without significantly impacting workflows. At the same time, all parties involved benefit from additional advantages such as automated data collection, improved traceability, and optimized recall processes.

For pharmaceutical manufacturers, packaging service providers, and all players in the supply chain, serialization does mean an initial investment and adjustment effort. However, the resulting safety for patients and increased confidence in pharmaceutical care more than compensate for this effort. The EU Falsified Medicines Directive could also serve as a blueprint for other regions of the world that also want to join the fight against counterfeit medicines.

Pharmaceutical serialization protects patients while optimizing your processes. Talk to our experts about customized labeling and verification solutions that meet the highest quality standards and are economically viable at the same time.

Check now instead of correcting later.

The most common serialization errors can be avoided with a quick system check.