Counterfeit drugs – countering the lies

pharmafile | February 4, 2019 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  Counterfeit drugs, IP, counterfeit medicines, falsified medicines, intellectual property, law, legal, patent 

As the Falsified Medicines Directive comes into effect in February 2019, Louis Goss fact checks ‘common sense’ claims on counterfeit drugs

If you were to read the news, you might be led to believe that ‘counterfeit medicines’ should be of major concern. The image painted is one in which sophisticated criminal networks introduce a constant stream of huge quantities of ‘fake drugs’ into the legitimate pharmaceutical supply chain, without concern for the many lives that they harm.

However the issue is much more complex than it seems. Statistics on the prevalence of falsified medicines remain muddled and incomplete. Meanwhile, legislation responding to the scourge of so-called ‘counterfeit drugs’ has in the past been used to bolster intellectual property (IP) rights and prevent generic drug makers from entering the market.

Thus, in discussing the issue of ‘counterfeit drugs’, clear definitions are a necessity. The World Health Organization (WHO) has followed this line of thinking since 2017. In discussing so-called ‘counterfeit medicines’, the WHO now refers instead to ‘falsified’ medical products. As defined by the WHO, falsified medical products are: “Medical products that deliberately/fraudulently misrepresent their identity, composition or source.”

The term ‘counterfeit drugs’ has, however, been used as a catch-all term. As such, the WHO describes certain medical products that do not deliberately misrepresent their identity as either ‘substandard’ (“authorized medical products that fail to meet either their quality standards or specifications, or both”) or ‘unregistered/unlicensed’ (“Medical products that have not undergone evaluation and/or approval by the National or Regional Regulatory Authority (NRRA) for the market in which they are marketed/distributed or used, subject to permitted conditions under national or regional regulation and legislation”).

In contrast, the term ‘counterfeit drug’, as defined by Vishv Priya Kohli, an associate professor at CBS Law, describes a medicinal product that has violated IP laws. Kohli suggests a counterfeit drug is one that has “an unauthorised representation of a registered trademark on a product identical or similar to one for which the trademark is registered”.

Nevertheless, the ambiguity of the term ‘counterfeit drugs’ is particularly apparent when you remember that many large Swiss firms – including CIBA-Geigy, Sandoz and Roche – were in the past accused of counterfeiting medicines themselves, due to the practice, common among Swiss companies, of copying German inventions and then exporting them back to Germany. This practice, which was especially prevelant among Swiss drugmakers in the early 20^th century, came to an end after Germany pressured the ‘pirate state’ into amending its laws.

Intellectual Property

Christa Cepuch, Pharmacist Coordinator at Médecins Sans Frontières (MSF), explained: “There has been a move away from using the term counterfeit when we talk about medicines quality. IP issues, such as counterfeiting and trademark infringement, are irrelevant to public health and we keep them outside the discussion surrounding poor quality medicines. The language has evolved.  Today we use the terms substandard and falsified, terms which came out of a very long debate at the WHO, among member states, which was part of an effort to clarify language and get rid of the IP angle and terminology of counterfeit.”

She was clear in stating: “IP issues are of no public health relevance and they are really outside the discussion around the quality of medicines, which is the discussion that we engage in.”

However, there is no doubt that the terminology surrounding counterfeit medicines had been misused in the past. As noted by Cepuch: “The evidence was that we saw the generic medicines being seized and quarantined… there were cases where shipments of legitimate generic medicines were being seized and quarantined because they were purported, or called, or confused to be counterfeits. This happened a couple of times around the world. But they were in fact generic medicines legitimately on their way to programmes in low and middle income countries.”

The issue came down to definitions: “In the past, there were some what they called at the time, anti-counterfeiting policies, which mixed up the issue; they called every kind of IP infringement a counterfeit medicine. However there are many different kinds of intellectual property. Trademark is one, but you also have copyright and patents and I don’t know how many other kinds of IP. Thus if you say that any infringement of IP becomes a counterfeit, it’s false. Counterfeit, as defined by the World Trade Organization, is trademark infringement and that has nothing to do with the quality of medicines. So the risk was that if the definition of counterfeit meant any infringement of IP – that could also include patent. Patent is just one kind of IP.”

One such case prompted the governments of India and Brazil to launch trade disputes against both the Netherlands and the European Union, after Dutch authorities seized at least 19 shipments of legitimate generic medicines for various serious health issues, including drugs for cardiological conditions, HIV/ AIDS, schizophrenia and dementia. It was alleged that imprecise anti-counterfeiting legislation was hindering healthcare programmes in poor countries and disrupting international trade. Furthermore, it was suggested that pharma companies were to blame.

As stated on MSF’s website in a post from 3 April 2011: “Major US and European pharmaceutical companies have a vested interest in limiting competition from generic drugs, and are using increased enforcement of intellectual property laws as a tool to clamp down on the legitimate trade in high-quality generic medicines between developing countries.”

In seeking to explain the actions of these firms, Cepuch suggested: “I think it’s just to protect their own. They’re always seeking for protection and enforcement, and this sort of angle [assists them in their aims]… I guess to paint this picture that somehow the quality of medicines is owned by the trademark holder or the patent owner. That has nothing to do with the quality of medicines.”

Fake drugs?

Fortunately, at least in regards to the law, the situation is said to have changed. An outcry from healthcare professionals pushed progress in this regard. As noted by Cepuch: “It was awareness of the problem of confusing and confounding the language around quality of medicines, and having legitimate shipments of generic medicines being seized and called counterfeit, that caused an outrage in public health circles. It was really quite astounding and that is when the debate and the member state mechanism on that issue started.”

Equally, grassroots campaigners were able to enact change. “In Kenya, something called an anti-counterfeiting law appeared to copy-paste some of this difficult language. Under that original anti-counterfeit law, counterfeit medicines were included under IP infringement. It was the same kind of language cropping up here and there in different countries and different IP policies and anti-counterfeiting policies. There was an interesting court case in Kenya, in the high court where people living with HIV took the anti-counterfeiting agency to court in protest against the language in that anti-counterfeiting act… The activists won.”

However, this has not prevented the use of vague terminology. Significantly, pharmaceutical companies, regulators and media outlets continue to use the term ‘counterfeit medicines’ in an imprecise and unclear way. The term is used interchangeably, to describe both ‘falsified’ and ‘substandard’ medical products. According to German firm Boehringer Ingelheim, counterfeit drugs may “contain a different quantity of the original active ingredient; contain totally different active ingredients; contain toxic ingredients; bear forged manufacturer’s data on the packaging; have been completely repackaged; have been produced under conditions that do not conform with current Good Manufacturing Practice (cGMP); have not been transported and stored properly.”

In lumping both falsified and substandard medicines together, these broad definitions result in misleading statistics on the scale of the problem of so-called ‘counterfeit drugs’. This was apparent in a recent report by the WHO. The 2017 report found that an estimated one in ten medical products in low- and middle-income countries is substandard or falsified. As expanded upon by Cepuch: “[The WHO] came out with a report just over a year ago now and they summarised the literature that they could find on substandard and falsified medicines. Unfortunately they mixed it all together. The issues of substandard medicines and falsified medicines are in fact very different but they mixed them into one statistic.” Research suggests that instances of substandard medicines entering the supply chain are much more prevalent than instances of falsified medicines entering the supply chain. As stated in a 2013 study published in the journal BMJ Open:“Substandard medicines represented the bulk of defective medicine incidents, accounting for over 95% of the cases.”

However as noted by Cepuch: “Even if you had substandard medicines on the market you wouldn’t necessarily know unless you tested all of them, because you have to know how much of the medicine is contained in the tablet or liquid, so it’s kind of an impossible question.”

Furthermore, the catch-all terms ‘fake drugs’ and ‘counterfeit medicines’ obscure the reality of the situation and thus make it more difficult to reach a solution. Michael Deats, group lead for the SSFFC Surveillance and Monitoring, Safely and Vigilance, Essential Medicines and Health Products at the WHO, reiterated a similar point in asking: “How many of these things are down to bad manufacturing or bad storage or bad transportation and how many of these things are just unregistered? They might be registered in the country next door, it makes them illegal but the health risk is probably low. You need to understand those different categories because there are very different responses to dealing with each of those categories.”

Thus, for Cepuch, ensuring the safety of medicines is the primary concern: “Honestly, we don’t talk about counterfeit medicines anymore. We talk about the quality of medicines, but even in MSF we don’t talk about falsified medicines. It’s not an issue that we see very frequently in our programmes and we’re more concerned about quality of medicines from a viewpoint of substandard medicines – making sure that medicines are manufactured properly and regulated in the market – and that is the focus of our policies.”

With this in mind, in tackling the wider issue of substandard drugs, the priority should be ensuring “good manufacturing practices and strong regulatory agencies to monitor and evaluate the process of manufacturing and storing medicines”.

Falsified Medicines Directive (FMD)

Despite the problems discussed so far, the real issue of falsified medicines entering the pharmaceutical supply chain is a legitimate concern. The issue came to the forefront in 2007, when it was discovered that 2.1 million doses of falsified prescription medicines had entered the pharmaceutical supply chain in the European Economic Area (EEA). The falsified drugs – imitations of Sanofi Aventis’ Plavix (clopidogrel), Eli Lilly’s Zyprexa (olanzapine), and AstraZeneca’s Casodex (bicalutamide), used for the treatment of psychosis, heart disease and prostate cancer – contained between 50-80% of active pharmaceutical ingredients along with unknown impurities.

The complex scheme involved a web of companies in different parts of the world, through which a small cadre of international businessmen, with a sophisticated knowledge of the pharmaceutical industry, shipped falsified medicines into the EEA. While no deaths were recorded in connection with the falsified medicines, the fact that substandard medicines entered the legitimate pharmaceutical supply chain is concerning.

As such, the implementation of the FMD – legislation aimed at preventing the entry of falsified medicines into the pharmaceutical supply chain across the EEA – may be a useful step in securing the supply chain. The legislation, which comes into full effect on 9 February 2019, will require all prescriptions medicines to carry a unique barcode, which must be scanned and decommissioned when the associated medical product is dispensed. Medical products must also be equipped with a visible anti-tampering device. Notably, the FMD does make a distinction between ‘counterfeit’ and ‘falsified’ medicines, in placing focus entirely on the latter.

There are, however, a number of issues with the FMD. Significantly, the MHRA has estimated that implementing the FMD may cost as much as £472.3 million over the next ten years. Meanwhile all UK dispensaries will be required to invest in as many as two to three scanners – which the MHRA estimates will come at a cost around £1,300 each, including software.

Furthermore, the British Medical Association (BMA) has warned that the FMD might result in tiresome delays: “The General Practitioners Committee of the BMA has concerns the authentication system will result in burdensome bureaucracy for pharmacists, practices and dispensing doctors and that it will not fit in with current pharmacy/dispensary IT systems. This is likely to result in an increase in the time taken to dispense, thereby representing an increase in workload.” These delays will likely result in further, additional costs.

The FMD does, however, increase the ease with which recalls are enacted and warn dispensers if drugs are close to their expiry date, or if they have already expired. The FMD also goes some way towards addressing the issue of illegitimate online pharmacies, through which a significant portion of falsified drugs are sold. The FMD ensures that all legally operating online pharmacies must use a common logo which must be displayed on every page.

Nevertheless, many falsified drugs are purchased through illegitimate online retailers by customers who are aware that the vendor they are buying from is not in line with the law. Many of these customers purchase drugs through these illegitimate online vendors in order to obtain medicines that they would otherwise not be prescribed.  

For example, the MHRA seized 6.2 million “counterfeit and unlicensed medicines” in 2015. While it remains unclear as to what proportion of the drugs seized were ‘counterfeit’ in comparison to those which were unlicensed, one third of the medicines seized (two million doses) were erectile dysfunction drugs. Meanwhile, slimming drugs, narcolepsy pills (used by students for ‘cognitive enhancement’), abortion pills, cancer medications (used by some bodybuilders to reduce breast tissue), and medical devices (including fake condoms) featured prominently on the list. It is not clear as to whether the drugs seized were in fact substandard. Either way, the FMD does not prevent customers from knowingly purchasing falsified drugs from illegal sites. 

Protecting public health

Overall, research suggests that substandard medicines are much more prevalent than falsified medicines, or ‘counterfeit’ drugs. In the UK in particular, contamination of medicines was by far the major concern. Significantly, of the 280 incidents involving substandard medicines, recorded between the years 2001 and 2011, just 11 incidents involved falsified medicines. In contrast, there were 60 incidents involving contaminated medicines.

Nevertheless, there is still insufficient data as to the true extent of the problem of ‘falsified medicines’ around the world. Thus, in securing the pharmaceutical supply chain the FMD might be considered a step in the right direction. However in addressing the broader issue of quality of medicines in the EEA, efforts towards ensuring good practice in regards to both manufacturing and the supply chain may be more effective, particularly when it comes to protecting public health.

Louis Goss