Taking stock of counterfeit medicines
Criminals who trade in fake medicines are finding ever more sophisticated ways to infiltrate legitimate supply chains. And pharmaceutical companies and regulators are developing ways to stop them.
Source: SINOPIX PHOTO AGENCY LTD/REX
In June 2013, two large boxes containing 150,000 packs of Postinor 2 were discovered at Lagos international airport by the Nigerian drug regulator. The product, a widely used emergency contraceptive containing levonorgestrel, contained no active ingredient. Similar batches have been detected in Ghana, Kenya and Angola. Fortunately, the batch at Lagos airport will not lead to any unplanned pregnancies or botched abortions in countries with limited healthcare resources.
Elsewhere, a hospital in Central Africa noticed that the mortality rate from acute malaria was higher than expected. Patients were inadvertently being treated with counterfeit antimalarials.
The problem of counterfeit medicines is not confined to the developing world. In April 2014, falsified vials of the breast cancer treatment Herceptin were found in Europe after Herceptin vials had been stolen in Italy and tampered with. Roche, the maker of Herceptin, performed a chemical analysis on one of the vials and found that it did not contain trastuzumab. Although none of the vials reached patients in the UK, affected batches were recalled as a precautionary measure.
“There is an iceberg out there,” declared Kenneth Leiper, a pharmaceutical quality assurance consultant, who chaired a conference in London in May on falsified medicines. The meeting was hosted by the Joint Pharmaceutical Analysis Group, a not-for-profit organisation of pharmaceutical analysts, sponsored by the Royal Pharmaceutical Society and the Royal Society of Chemistry.
At the conference, David Shore, a former police officer, who is acting senior director for Pfizer Global Security, EMEA (Europe, the Middle East and Africa), presented photographs of run-down factories in China, Pakistan and Colombia used by counterfeiters to manufacture medicines. Some of the ingredients found in the counterfeit products found on site included brick dust, paint, floor wax and pesticides. “Counterfeiters don’t care what they put in it, they care about the profits.”
The internet is proving to be an effective medium for counterfeiters to bypass the security of the legitimate medicines supply chain (stocks held by licensed wholesalers or pharmacies in community and hospital settings). However, this supply chain has also been breached. According to data from the UK Medicines and Healthcare products Regulatory Agency (MHRA), between 2004 and 2011 there were ten incidents in the UK in which medicines supplied to patients were recalled because they were falsified. Over the same period, there were a further seven incidents relating to products seized before they reached UK patients (see timeline). “These cases only relate to counterfeits entering the legitimate supply chain and do not include the illicit supply of medicines through other routes, which is so broad that you can’t quantify it,” an MHRA spokesperson said.
According to data collected by the Pharmaceutical Security Institute, a body created by pharmaceutical companies to monitor the market for imitation medicines, the number of worldwide incidents has rocketed from 196 in 2002 to 2,018 in 2012 (see ‘Cases of counterfeit medicines worldwide’ bar chart).
The meeting heard that, as of 31 March 2014, counterfeits of Pfizer’s medicines have been found in 107 countries, and breached the legitimate supply chain in 60 countries. Counterfeiters have targeted a wide range of Pfizer’s therapeutic products, including the Alzheimer’s treatment Aricept (donepezil), the lipid-lowering drug Lipitor (atorvastatin), the anticancer agent Sutent (sunitinib), the anxiolytic Xanax (alprazolam) and the anti-hypertensive Norvasc (amlodipine).
GlaxoSmithKline is also finding more of its products being counterfeited. In 2013, there were 500 worldwide instances of false GSK medicines, David Tainsh, chief product quality officer for GSK’s global product quality office, revealed. Law enforcement agencies conducted 307 raids on facilities globally, and made 272 arrests; up from 259 incidents, 94 raids and 129 arrests in 2009.
Tricks of the trade
The escalation in counterfeit medicine seizures has prompted regulators and pharmaceutical companies to target the problem aggressively. But their task is far from simple.
It is difficult to track counterfeiters — they might use several different planes to transit a single consignment. Batches are repackaged into smaller bundles at each stopover to thwart law enforcement agencies. In one incident, 160kg of counterfeit Lipitor was moved from China to Hong Kong, Dubai, the Bahamas and then on to the UK.
And it is not so simple to tell the genuine from the fake. Counterfeiters do not skimp on their packaging, since it is the first thing seen by regulatory inspectors and the public, says Tainsh.
Specific countermeasures being taken by the pharmaceutical industry include overt features, such as holograms, covert features, such as digital watermarks, and initiatives that track and trace products.
“It is absolutely right to defend our products but our overriding concern is for patient well-being,” says Tainsh.
Handheld devices that use a mix of spectroscopic and chemical analysis can be used to test products on the market, capability much needed in the developing world. “Lack of laboratory facilities in developing countries makes these countries vulnerable,” says Michael Deats, a former head of enforcement at the MHRA, who now works for the WHO’s department of essential medicines and health products.
Street-markets in Africa are “full” of counterfeit medicines, adds Deats. But the drugs on sale are not all fake. Some pharmaceutical company sales representatives sell their wares in street markets to meet sales targets “which adds a certain legitimacy to these street-markets”, Deats adds.
Deats also tells of cases where nurses have gone to such markets to buy medicines for hospitals that have run out of stock.
Even manufacturers officially licensed by a medicines regulator to produce a medicine can be involved in the production of counterfeits; Chinese authorities raided one facility making counterfeit Panadol, according to Tainsh.
Ron Guido, a brand protection consultant, who once worked with Johnson & Johnson, contends that contract manufacturing opens the door for “shadow operations”, with raw material suppliers seeking new customers. He also lists free trade agreements, a lack of regulations governing trade, under-resourced regulatory bodies and enforcement agencies, and a general disrespect for intellectual property in some countries as all contributing to the problem of counterfeits.
And traders in fake medicines are keeping atop of the latest developments in industry. Customs agencies are already finding counterfeit blood products, for example. And producing biologic medicines will probably not be beyond the capabilities of counterfeiters. “Because it is in a vial, it makes no difference,” says Deats.
Counterfeiters are attracted to a profitable business with little risk of a custodial sentence or other deterrents, although in the Chinese Panadol case, Tainsh points out that the counterfeiter received a 7-year custodial sentence.
Some known counterfeiters live lavish lifestyles. One was known to own a Learjet, while the counterfeit medicines trade can finance terrorism. For instance, counterfeiting medicines funded the Madrid train bombing in 2004, said Shore. Among the contraband seized in one Turkish raid in 2006, were counterfeit Viagra, 51kg of heroin, 378,000 ecstasy tablets and three assault rifles.
Patients may be driven to buy products of questionable quality from street markets or from the internet because they cannot afford the real medicine. “Affordability must be a contributing factor,” says Deats, “but very cheap products are counterfeited too, so it is not just the expensive products. “A study is needed to look at the drivers and why certain products are focused on.”
“We need to find ways to lower the costs of medicines for people,” says Tainsh. “But we have also found that if there is a drug shortage, counterfeiters will fill the gap.”
The World Health Organization used to estimate that 1% of sales in developed countries were counterfeit medicines, rising to over 10% for some countries in the developing world. It has also estimated, in a 2012 factsheet, that 50% of medicines available from websites that conceal their address are counterfeit.
The WHO no longer puts a figure on prevalence, stating that the true extent of the problem is not known. However, it is working on a project — the SSFFC (substandard, spurious, falsely labelled, falsified and counterfeit medical products) surveillance and monitoring system — to gather better data.
“If you Google ‘falsified medicine’, you can find a lot of statistics, but these are estimates,” says Deats.
“[For] some of the statistics, I can’t find the evidence that underpins it. We need to do detailed work on this,” Deats says.
The WHO has created an electronic “rapid alert form” to collate data on cases from member states. It contains 30 questions, including whether the case has been reported to healthcare professionals, whether it has had an effect on public health, and who is investigating it.
The WHO surveillance system is being used by 85 countries, with a further 15 countries coming on board by the end of 2014.
As of May 2014, the WHO surveillance system project has identified 335 counterfeit products. Once the number reaches 1,000, Deats predicts that the WHO will release some statistics on the prevalence of counterfeit medicines globally.
The Falsified Medicines Directive, which came into force in 2013, will be an important instrument in protecting European citizens (see ‘Your RPS’). The directive covers a range of measures aimed at preventing falsified medicines entering the supply chain, including improved inspections, better control of intermediate steps in the supply chain, measures to enable the identification of legitimate internet sellers and the authentication of medicines. The directive’s implementation in the UK is expected in 2017.
In Europe, organizations representing pharmacists, pharmaceutical companies and wholesalers are working together to create a medicines verification system (EMVS), which assigns a unique identifier to each pack of product to ensure medicines in the supply chain are making it safely from the point of manufacture to the patient.
“[The EMVS] is the biggest IT system project for patient safety,” says Sid Dajani, a pharmacist who represents the Royal Pharmaceutical Society on the Pharmaceutical Group of the European Union, a body that represents community pharmacists in 33 countries, and which is involved with the verification system.
The “bad guys survive on visibility”, says Stephen Truick, an internet infrastructure manager at the MHRA. Truick spends most of his day closing down websites that sell counterfeit medicines.
He gave the example of how he found a You Tube video explaining erectile dysfunction, with 91,156 views, and containing a link to a website selling Kamagra. He closed the site down. “If we all put resources into it, we can make a difference.”
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11138907
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