Stepping Up the Fight Against Counterfeits

Despite receiving increased regulatory attention, counterfeit medicines remain a serious and ongoing global health threat. The World Health Organization (WHO) defines them as medicines that have been deliberately and fraudulently mislabelled with respect to their identity and/or source (1). Such illicit products range from random mixtures of harmless, inactive substances to toxic preparations that can result in death. Counterfeit medicines are found everywhere in the world, although the scale of the problem varies from region to region.

Criminal gangs are attracted to pharmaceuticals because of the high value of medicines and the relatively low risk of prosecution (2); as the counterfeiting business operates on an international scale, it is difficult to tackle the source of the problem and apprehend the parties involved. Furthermore, since many countries have failed to enact deterrent legislation, counterfeiters have felt free to act with impunity and have often managed to evade justice.

European supply chains breached

Counterfeiting has traditionally been most prevalent in regions where the regulatory and enforcement systems for medicines are at their weakest, which includes many African countries, as well as parts of Asia and Latin America. In contrast, counterfeiting levels in most industrialised countries (e.g., EU countries, the US, Australia, New Zealand, Canada and Japan) tend to be low thanks to effective regulatory systems and market control. Consequently, many anticounterfeiting strategies have tended to focus on the areas where counterfeit pharmaceuticals are most prevalent.

However, the supply chains of industrialised regions are now under threat, with several highprofile court cases in 2011 highlighting the efforts that counterfeiters are willing to make to break into high-value pharmaceutical markets. These cases have brought a renewed sense of urgency to the fight against counterfeiters.

In 2011, the Medicines and Healthcare products Regulatory Agency (MHRA) revealed the extent to which the UK is now being targeted by counterfeiters. In one country-wide crackdown, the agency reported that over a million doses of medicines worth approximately €2.4 million were seized in raids by enforcement investigators (3). Counterfeit Valium and Viagra were the most commonly sold fakes, but counterfeiters were also targeting major therapeutic areas such as cancer, cardiovascular disease, respiratory disease and depression.

The MHRA's success against counterfeiters was illustrated by the culmination of a case that has been described as the most serious counterfeit medicine fraud in the EU (4). A criminal gang had attempted to target the UK by bringing in two million doses of counterfeit drugs from China. The plot was highly sophisticated, with the products closely resembling genuine medicines, and was considered the worst breach of the UK's regulated medicines system. Approximately 72000 packs of counterfeit medicines with a retail value of around €5.6 million actually managed to enter the UK supply chain between December 2006 and May 2007. It was only thanks to international cooperation over a tip off that the criminal network was broken up. In May 2007, a licensed pharmaceutical packager in the UK was repacking a wholesale consignment of the antipsychotic drug Zyprexa when he noticed anomalies in the packaging (5). He informed the drug's manufacturer, Eli Lilly, who were suspicious about the findings and immediately contacted the MHRA. The regulator's enforcement team then impounded the consignment. Upon testing, it was found that the fake Zyprexa tablets contained various impurities, as well as only 55–80% of the API (5). This led to the MHRA's first ever Class One Drug Alert recall for the fake batch of Zyprexa as it ordered all pharmacies and healthcare staff to ensure that the product was taken off the shelves. Over the following months, the investigation revealed a complex international supply route that led from Ireland via Belgium and Mauritius, and then to a location in London. At the same time, US investigators began to investigate the matter and revealed the Chinese source of the counterfeits.

Despite this success, the UK's BBC news has recently reported that not all the counterfeit products that entered the country's supply chain have been recovered. Following questioning of the MHRA using a Freedom of Information request, the regulators admitted that although the vast majority of counterfeit products had been recovered, some had been dispensed to patients (6). Eight patients who had received counterfeit Zyprexa or Plavix were identified, but the authorities are continuing to look for other patients who may have received such products. According to the BBC, the numbers could run into the thousands.

There are also continuing reports of other breaches of the system. At the end of last year, the MHRA announced that counterfeit versions of the HIV medicine Viread had been discovered in the UK market alongside earlier-reported Truvada counterfeit products (7). At around the same time, a Danish parallel importer withdrew stocks of Truvada following consultations with the Danish regulatory agency. So far, full details of the nature and source of the products have not been made public and there is no evidence that they reached patients.

Illegal online pharmacies have been a particular problem for the authorities. In November 2011, two men who had been running an illegal online pharmacy business were sentenced to 24 months in prison. The MHRA had run a 2-year surveillance initiative called Operation Aimee to expose the set up (8). Over this period, MHRA intelligence officers made large numbers of online test purchases of products to build up evidence for their case. When raids were finally conducted, 99220 tablets of counterfeit Viagra, Cialis and a number of other controlled substances were seized.

Fortunately, the MHRA were able to expose and close down this particular criminal network, but the consequences of the illegal online trade ended up being deadly for one unfortunate victim. In a tragic case, a young paramedic who was having trouble sleeping between shifts decided to look online to get quick access to medication. She bought an anti-depression drug that is also used for insomnia from an online site, but died after taking a few tablets (3). The case served as a reminder of the fine line between success and failure against the counterfeiters and the need for concerted action.

Renewed EU action

The fact that counterfeit products have managed to enter highly regulated markets has led to renewed efforts to tackle counterfeiting. Much hope has been placed in Europe's Falsified Medicines Directive, which will come into force in January 2013 and increase controls across the EU. The Directive was approved by the European Parliament last year and introduces new rules that will require prescription medicines to have safety features that enable verification of individual packs throughout the supply chain (9). Under the new system, all importers, manufacturers and distributors will become brokers of medicinal products, which confers greater responsibility on them to be vigilant and proactive. The Directive also targets illegal online pharmacies, which remain a major threat. In the future, all websites offering medicines for sale will need to be clearly linked to the website of the competent authority in that particular country. The regulatory body will also display a list of approved online sales sites, which will be required to display a common, recognisable logo (9, 10).

The pharmaceutical industry has also been working on a number of initiatives with other stakeholders. In January 2012, the European Federation of Pharmaceutical Industry Associations (EFPIA), the European umbrella organisation of pharmaceutical full-line wholesalers (GIRP), the European Association of Euro-Pharmaceutical Companies (EAEPC) and the Pharmaceutical Group of the European Union (PGEU), which represents pharmacists, issued a joint press release calling for practical and cost-effective solutions to implement the requirements of the EU's Falsified Medicines Directive (11). The organisations have been developing a European Stakeholder Model (ESM) that can be adapted to individual national systems. ESM employs a product verification system that is run by pharmaceutical manufacturers, pharmacists and wholesalers, as well as parallel distributors. A unique serial number will be featured on each product pack that can be checked with ease against a central database at the point of dispensing. A pilot of the system was conducted in Sweden during 2009 to 2010 and a further pilot is planned for Germany in 2013 (11).

Another major development that has received the industry's backing is the MEDICRIME Convention launched by the Council of Europe. In December 2011, a high-level conference was held in Moscow where members signed up to binding international legal agreements to combat counterfeiting. In particular, it was felt necessary to tighten the definition of what constituted a counterfeit in order to fill gaps in certain national legislation. For example, in certain countries, it has been difficult to bring legal action against those manufacturing, distributing and selling falsified medicines because the existing legislation only covered breaches of trademark and patent legislation (12). EFPIA hopes that the timing of the MEDICRIME initiative will boost efforts at the EU level and has also stated that it is ready to help any members in meeting their obligations for the MEDICRIME Convention (12).

Outlook

The threat posed by counterfeits to the European supply chain cannot be underestimated and the number of cases in the UK alone last year shows that counterfeiters are continuing their efforts to break into regulated markets. On a positive note, the level of international cooperation to defeat the criminals behind counterfeiting is at an all-time high. The EU's Falsified Medicines Directive, the MEDICRIME Convention and the ESM initiative by industry stakeholders are just some of the notable cooperative measures that are set to improve protection of the supply chain.

References

1. WHO, "Medicines: spurious/falsely-labelled/ falsified/counterfeit (SFFC) medicines" (WHO website, 2010). www.who.int, accessed 8 Feb. 2012

2. N. Siva, The Lancet 376 (9754), 1725 – 1726 (2010).

3. T. Symonds, "Fake medicine trade: UK crackdown on drug importers" (BBC News, 2011). www.bbc.co.uk, accessed 8 Feb. 2012

4. BBC News, "Man jailed for £4.7m counterfeit medicine fraud" (BBC News Website, 2011). www.bbc.co.uk, accessed 8 Feb. 2012

5. N. Siva, "How investigators unravelled Europe's biggest-ever fake-medicine scam" (Wired, 2011). www.wired.co.uk, accessed 8 Feb. 2012

6. P. Kemp, "Fake drugs given to NHS patients still untraced" (BBC News, 2012). www.bbc.co.uk, accessed 8 Feb. 2012

7. MHRA, "Counterfeit drug peddlers sentenced" (MHRA Press Release, 2011). www.mhra.gov.uk, accessed 8 Feb. 2012

8. P. Taylor, "Counterfeit Viread also on market, says MHRA" (Securing Pharma Website, 2011). www.securingpharma.com, accessed 8 Feb. 2012

9. G. MacDonald, "EU falsified meds act formally adopted" (In-Pharmatechnologist Website, 2011). www.in-pharmatechnologist.com, accessed 8 Feb. 2012

10. "Q&A: Directive on falsified medicines" (European Commission, 2011). http://europa.eu, accessed 8 Feb. 2012

11. EFPIA, "EAEPC-EFPIA-GIRP-PGEU working for better Patient Safety" (EFPIA Website, 2011). www.efpia.eu, accessed 8 Feb. 2012

12. EFPIA, "MEDICRIME Convention Position Paper of the European Federation of Pharmaceutical Industries & Associations" (EFPIA Website, 2011). www.efpia.eu, accessed 8 Feb. 2012