From blueprint to reality

To counter the threat of counterfeit and fake medicines entering the pharmaceutical supply chain, notably via internet pharmacies, the European Union has introduced the False Medicines Directive (2001/83/EC). The first line of defence will be pharmaceutical packaging, using technologies such as tamper-evident labelling, and France's CIP-13 system and ECC 200 2D Data Matrix barcodes

The FMD takes product identification beyond batch level, mandating that every single product carries a unique code

The Falsified Medicines Directive is set to have a considerable effect on pharmaceutical manufacturers. Craig Stobie, lifesciences sector manager, Domino Printing Sciences, looks at the major areas of impact.

The battle against counterfeit and fake medicines is an ongoing one, and the scale of the problem is growing. This is mirroring the growth of a global pharma market riding a wave of expansion, particularly in Asia, where consumers are enjoying higher disposable incomes. According to the WHO, up to 25% of medicines sold in developing countries are counterfeit, reaping earnings in excess of US$32bn (€23bn); other estimates value the worldwide market for illegal drugs at $75–$200bn (€54–€144bn). The human costs are also high: counterfeit medicines are thought to kill more than 100,000 people annually, most of them in poorer countries.

Of equal concern is the opinion held by some in the pharma industry that current strategies to tackle the problem do not go far enough: according to research by Pfizer and the International Pharmaceutical Federation, 63% of pharmacists in Europe, the US and Australia believe this.

Such pessimism is unwarranted, however, because two events in 2011 provide powerful evidence that governments are determined to get to grips with the problem by enacting important legislation to secure the pharmaceutical supply chain. At the beginning of the year, France implemented its CIP-13 system, whereby the external packaging of every pharmaceutical product sold in the country must carry much more information than before: namely, a data-matrix barcode plus three lines of human-readable text – made up of the CIP-13 code, batch number and expiration date.

Six months later, on 1 July, the EU passed into law the Falsified Medicines Directive 2001/83/EC. (The term ‘falsified’ describes medicines that may not contain active ingredients, or contain them in the wrong quantities.) The FMD incorporates a series of initiatives to help safeguard the supply chain and protect patients. Among the most significant for manufacturers will be the introduction of obligatory identification and authenticity features on outer packaging of medicines, including a unique, non-predictive number and tamper-evident labelling.

In a major enhancement to France’s CIP-13, the FMD takes product identification beyond batch level, mandating that every single product carries a unique code – effectively creating the ‘batch of one’. How the unique number for each product is generated – sequentially or randomly, for example – is left up to the manufacturer. When the dispensing pharmacist scans the barcode the data is transmitted to the manufacturer’s database as a simple request to confirm that the data on the pack matches the data held by the manufacturer. If it does, the medicine is genuine.

The FMD is notable for its scope, covering not just original pharmaceutical manufacturers but distributors, re-packers and contract packers. All of these parties will now have to comply with the same IT infrastructure. It also addresses the sale of falsified medicines over the Internet, obliging legal online pharmacies to display a ‘trust mark’ on their website. Clicking on this takes consumers to an official register of legal pharmacies, and by clicking on the entry in the register the consumer returns to the website of the legal pharmacy.

Other key measures include more stringent record-keeping for wholesale distributors, and a stronger inspection regime. Manufacturers and distributors will have to report any suspected falsified medicines via a rapid alert system.

Starting from 1 July, EU member states have 18 months to transpose the FMD into national law, and manufacturers then have three years to become compliant. All this protection comes at a price for all the players in the industry. Between 2013 and 2020, the European Commission estimates that manufacturers and importers of medicines will pay between €6.8bn and €11bn, while the cost to pharmacies will be €157m and to wholesale distributors €280m.

But while the timetable is fixed, there are still vital details to be finalised concerning the precise nature of the identification features that medicines will have to incorporate. At the time of writing, all we know for certain is that a key element will be a pan-European requirement for unique serial numbers on each pack. While it is very likely that the data carrier will be the ECC200 2D Datamatrix barcode – as used in CIP-13 – other barcode formats have been discussed, as has RFID, although the latter is certainly a non-starter.

It is likely that the data carrier will be a 2D Datamatrix barcode

There is also ongoing debate about the most suitable standard to underpin a coherent global track-and-trace system; the most commonly mentioned are GS1 and EPC, with the former probably being the front-runner.

The details may be unclear, but it is becoming very obvious that the combined impact of the CIP-13 and the FMD changes the game for pharmaceutical manufacturers and their packaging converters. Take the question of the capacity of existing production lines to handle the new requirements. On most lines space is at a premium, so it is difficult to retrofit new coding equipment, and even where it is possible the result might well be a mish-mash of interfaces.

According to one estimate, up to 80% of the coding solutions installed in pharmaceutical and healthcare packaging operations will be rendered obsolete by the FMD; according to another, up to €10bn will have to be invested in modifying or replacing production lines and associated coding systems. Meeting these costs will be particularly challenging for small to medium-sized operations.

A further fundamental issue is that of managing the serialisation that drives the authentication process at the heart of the FMD. Manufacturers can no longer leave this to their packaging supplier; they have to take responsibility for generating the data, keeping it secure and, in partnership with the packaging operation, ensuring that after printing and code verification, it can be easily retrieved.

The tight timetable imposed by the FMD means that pharmaceutical manufacturers have a lot to do in a relatively short time, and they need all the help they can get from the coding industry. Fortunately, the implementation of measures such as CIP-13 in France – plus similar schemes in Turkey, Italy, India, Brazil and China – means there is a well of expertise on which they can draw.

Craig Stobie

Domino, for example, has created a new group dedicated to FMD implementation, consolidating its experience of legislative compliance solutions. The group includes specialists in all the critical disciplines, including legislative standards, validation of automated manufacturing good practice, code formats and serialisation.

This broad range of skills reflects the need for an ‘holistic’ approach to complying with the FMD, which brings together IT, materials science, packaging design and coding technology. Where serialisation is required, a unique tracking number needs not only to be generated and printed on each pack, but also scanned to verify its readability. The information is more comprehensive and its presentation more sophisticated, which has an impact on the physical design of the label, the choice of coding technology and its suitability for the packaging materials involved.

Even in less complex applications, a number of factors must be taken into account to ensure that packaging performs its dual role of physically protecting the product, and protecting the brand itself, through measures to prevent counterfeiting or increase shelf appeal.

Finally, one interesting issue that is emerging from Domino’s work with clients on the FMD is that the OEM-dependent nature of many packaging solutions is going to be a significant factor in the process. OEM agreements have become more common as integration between packaging and coding specialisations has become more technically sophisticated, allowing companies to incorporate the best technology into their solutions without developing it themselves from the ground up.

An accepted element in new production lines, OEM-sourced components are expected to figure prominently in upgrades to existing facilities to gain FMD compliance. Manu-facturers should be aware that while OEM solutions offer technological benefits, the relationship between the manufacturers of all equipment (host machine, coding and inspection devices) and the end user makes managing the project even more important.