Deadly Imitations
by Matías Loewy

Counterfeit drugs are a growing global enterprise and a major threat to health in both the developed and the developing world.

In December 2004, 22-year-old Veronica Díaz went to a local hospital in the Patagonian province of Río Negro to get her seventh shot of Yectafer, an injectable iron supplement she had been prescribed for anemia. The medical tragedy that ensued sent shock waves across Argentina.

The injection produced liver damage so severe that Díaz required a liver transplant. She died on Dec. 23, 2004, before the operation could take place. At least eight other women were hospitalized in the same region with similar adverse reactions, and a second fatal case was reported in the province of Entre Ríos.


(Photo by Armando Waak/PAHO)

"I think my hair turned white that day," recalls José Blanc, then technical director of the local subsidiary of AstraZeneca, Yectafer's manufacturer. He was convinced from the start that the lethal drug could not have come from his laboratory, since each lot went through no fewer than 50 quality checks before being released into distribution. The product had been on the market for 40 years, with more than 20 million doses administered in Argentina alone.

"Nothing like this had ever happened before," said Blanc, now Astra-Zeneca's director of quality control for Latin America and the Caribbean.

Argentine health authorities retrieved samples of the suspicious product and sent them to Buenos Aires for analysis. When Blanc saw the samples, he says it took him "less than 30 seconds" to confirm his suspicions that the drug was fake. The lot number and expiration date were printed in the wrong place, and the name was printed in the wrong size font. The maroon-colored liquid inside was a different shade from the original drug.

Subsequent analysis showed that instead of iron sorbitol, the active ingredient in legitimate Yectafer, the counterfeit ampules contained another iron derivative in a concentration three times as high as in the original. Authorities managed to identify and prosecute several members of the counterfeit drug's distribution chain. But those who actually produced the drug were never caught.

More than a year after Veronica Díaz's death, Blanc's sense of indignation toward those responsible has not diminished. "Even if they don't mean to kill people, they're true criminals," he says.

Global scourge

The manufacture, distribution, and marketing of counterfeit drugs have become a lucrative and growing business worldwide. The problem is most serious in countries where regulatory oversight and law enforcement are weak. In most industrialized countries, counterfeit drugs amount to less than 1 percent of the total market in pharmaceuticals. But in many countries of Africa, Asia, and Latin America they are believed to represent 10-30 percent of the total drug market.

"Obviously it must be a very lucrative activity for counterfeiters to go to so much trouble," says Adrián Giménez, a Buenos Aires prosecutor whose unit has handled more than 400 cases of counterfeit drugs since 1997.

In the PAHO region

According to recent reports, drug counterfeiting is growing in the Americas and around the world even as efforts to address the crime are increasing. Here are examples of recent developments in member countries of the Pan American Health Organization (PAHO):

  • The Association of Colombian Pharmaceutical Industries estimates that in 2004, $60 million worth of medicines-5 percent of all drugs sold-were contraband, counterfeit, or adulterated.
  • In the Dominican Republic, about half of all pharmacies operate illegally, and 10 percent of medicines imported in 2005 were fake, according to the Ministry of Public Health. Some confiscated medicines had expired more than 10 years earlier.
  • El Salvador's Association of Pharmaceutical Companies reports that counterfeit drugs are widely available on the domestic market. According to a local manufacturer, Gamma Laboratories, fake drugs generated some $40 million in losses to El Salvador's pharmaceutical industry in 2005.
  • Mexican federal agents seized 60 tons of stolen, expired, and counterfeit pharmaceuticals in just two states, Michoacán and Jalisco, in 2004. Reports indicate that illegal products represent about 10 percent of the pharmaceutical market nationally.
  • In Peru, the sale of counterfeit drugs rose from an estimated $40 million in 2002 to $66 million in 2006, according to the Association of Pharmaceutical Laboratories of Peru. In Lima alone, the number of illegal pharmacies selling counterfeit medicines has increased from about 200 in 2002 to 1,800 today. Peru's General Directorate of Medicines, Supplies and Drugs seized some 460,000 counterfeit or expired medicines in 2005.

Despite its growth, counterfeiting has remained a relatively low-profile crime. Since counterfeit drugs are generally difficult to detect, reporting on the problem is erratic. Legitimate pharmaceutical manufacturers cooperate with one another in collecting data on known cases. But "in the past they were reluctant to share information publicly or to sound the alarm too loudly, because that could undermine public confidence in legitimate medicines," says Rosario D'Alessio, regional advisor for medicine and pharmaceuticals at the Pan American Health Organization (PAHO).

Now, "that is changing-the fight against counterfeiting is intensifying with the support of the pharmaceutical industry," D'Alessio says.

Marcelo Peretta, vice president of the Federal Capital Association of Pharmacists and Biochemists in Buenos Aires, believes that the low-profile nature of counterfeiting may be part of its draw for criminals.

"Making counterfeit drugs is more appealing than trafficking in cocaine or other illegal drugs because counterfeiters are not pursued as aggressively and they're part of a circuit in which they can launder their money faster," Peretta says.

Counterfeit drugs have produced tragic consequences across the globe. In 1995 in Niger, 2,500 people died after receiving a counterfeit meningitis vaccine. In Haiti the same year, 89 people died after taking a cough syrup that contained diethylene glycol, a toxic chemical used in antifreeze. Three years later, the same cough syrup killed 30 infants in India.

According to the World Health Organization (WHO), 60 percent of counterfeit drugs are found in developing countries. A high proportion of the fakes are drugs used to treat malaria, HIV/AIDS, and other diseases that disproportionately affect the developing world. A study in WHO's Southeast Asia Region showed that 38 percent of the 104 antimalarial drugs on sale in pharmacies contained no active ingredients at all.


A key challenge in the fight against counterfeiting is to develop systems that can trace medications through all the stages of the drug chain.

But any drug can inspire imitators, and no country is exempt from risk. In March 2005, investigators discovered an international network that was manufacturing fake tablets of Lipitor (a cholesterol reducer) in Costa Rica for shipment to the United States, where they would have sold for some $8 million. Pills for erectile dysfunction, often sold over the Internet, are also a favorite target for counterfeiters. Indeed, medicines purchased over the Internet from sites that conceal their physical addresses have been found to be counterfeit in more than half of cases.

"The problem is growing," says D'Alessio. "There's local production, but there's also international traffic in counterfeit drugs. The fact is that counterfeiting of drugs is globalized."

Criminal effects

In many cases, counterfeiters produce nearly exact replicas of a legitimate drug, copying every detail from the form—pill, cream, syrup, or injectable solution—to the packaging and labeling. A recent study in The Lancet medical journal concluded that counterfeiters' abilities to imitate holograms and other sophisticated printing techniques had improved dramatically between 2001 and 2005, making detection even more difficult.

Counterfeit products may contain the correct or wrong ingredients, some or no active ingredients, or substitutions that may be benign, toxic, or lethal. In other instances, criminals may steal legitimate pharmaceutical products and later reintroduce them into distribution, with no guarantees they have been properly transported or stored. In some cases, the expiration date is changed to "lengthen" a drug's shelf life. Investigators have found that the distribution channels of stolen medicines are very similar to those of illegally manufactured drugs.

Labs in henhouses

Officials who investigate counterfeit drug cases say the job is full of surprises.

"In most cases, you find clandestine labs in simple sheds without any external identification," says Adrián Giménez, one of Argentina's most experienced investigators of counterfeit drugs. "But we also discovered a band of counterfeiters who were producing adulterated asthma medication inside a hen house."

In recent years, Giménez says, investigators have received a growing number of leads from doctors and other health professionals, who are becoming more alert to the problem. This was what happened in two recent cases involving counterfeit cancer drugs.

"One of them had no active ingredients, and the other was way past the expiration date and had been transferred to a new container," Gimenez says.

In both cases, it was doctors who noted something strange in the products' appearance and alerted authorities.

One of the most complex aspects of the problem is that, unlike the false Yectafer, many counterfeit drugs do not produce harm that is immediately apparent. Their lack of therapeutic effect may be confused with the natural evolution of an illness or with a patient's particular response to treatment, rather than identified as the result of ineffective medicine.

"In general, they may not kill, but they have no effect," explains D'Alessio.

Regular use of such medications can lead to drug resistance, therapeutic failure, or even death. In 1999, at least 30 Cambodians died after taking counterfeit antimalarial drugs that contained sulfadoxine-pyrimethamine (an older, less effective antimalarial) but that were sold as the newer, more effective artesunate.

The scope of the problem is difficult to assess because weaknesses in national drug surveillance programs make it hard to collect information, much less take action, on ineffective drugs. In 1997, Argentine authorities discovered several fake lots of Madopar, a medication for Parkinson's disease. When patients took the pills, their symptoms-trembling, stiffness, or slow movements-got worse.

"I am convinced that fake Madopar must have caused some deaths that simply went undetected," said Giménez, who investigated the case.

International battle

Countries around the world have responded to this growing global threat by stepping up efforts to detect, trace, and prosecute cases of drug counterfeiting. In 2001, Brazil's National Health Surveillance Agency (ANVISA) and PAHO carried out a survey to assess efforts to address the problem in Latin America and the Caribbean.

The responses to the survey-received from 15 of 23 countries approached-revealed serious shortcomings in countries' abilities to fight drug counterfeiting. Problems included an absence of national standards or guidance for the distribution and dispensing of medicines, a lack of formal structures for preventing and fighting this type of crime, and a lack of information for the public about counterfeit drugs known to be in circulation.

The results of the ANVISA-PAHO survey were presented in December 2001 at the founding meeting of the Working Group to Combat Drug Counterfeiting (WG/CDC). The group, coordinated by PAHO and made up of regulatory authorities and industry representatives from throughout the region, has met twice since then, most recently during the Fourth Pan American Conference on Drug Regulatory Harmonization in the Dominican Republic in March 2005. The group has also sponsored regional training workshops.

New global crackdown

The World Health Organization (WHO) is intensifying the war on drug counterfeiting with a new global task force that links the efforts of government and international agencies as well as the public.

Announced last September, IMPACT (International Medical Products Anti-Counterfeiting Taskforce) will enlist consumers, drug distributors, pharmacists, and hospital staff to help identify cases of counterfeit drugs.

IMPACT will start by looking at existing laws on drug counterfeiting and advising WHO member governments on how to strengthen those laws. The group will then target the corruption that keeps such laws from being enforced.

"We want to explain to corrupt officers that they should not accept bribes because the fake drugs they let through could end up poisoning their own families," says Valerio Reggi, of WHO's Health Technology and Pharmaceuticals program and coordinator of IMPACT.

Some of the task force's key challenges will be persuading consumers and health care providers to report suspicious products, getting legitimate drug manufacturers to make their products more difficult to fake, and improving the traceability of pharmaceuticals.

To make medications easier to trace, the task force will work with government agencies and manufacturers to create a product database and tracking system that uses widely available and relatively inexpensive technology. Producers will label each bottle or packet of medicine with a unique number, making it possible to check a drug at any point in the distribution pipeline and determine whether it is genuine.

The task force will include national regulatory authorities, law enforcement agencies, nongovernmental organizations, other international organizations, associations of pharmaceutical manufacturers and wholesalers, patient advocacy groups, and health care professionals.

Meanwhile, WHO is exploring the possibility of promoting an international accord-similar to the Framework Convention on Tobacco Control-or some other global cooperation mechanism that can catalyze wide-reaching international action against drug counterfeiting.

The WG/CDC has developed a series of recommendations for fighting counterfeiters. The group urges regulatory authorities to implement national programs for prevention and control that have defined plans of action, schemes for tracking drugs through the supply chain, policies on communicating the risks to the public, and the formation of networks to facilitate information dissemination and cooperation between various countries of the region.

The group also recommends that every country's ministry of health establish an "executing unit" made up of pharmaceutical inspectors, lawyers, and intelligence personnel to monitor the quality and safety of available drugs.

"Some of the recommendations can be implemented immediately, and others-like setting up executing units-will take more time," says D'Alessio. "But all the countries agreed to take action, in some cases starting by designating specialized teams within the ministries. This will facilitate regional exchange of information."

Critical measures

For pharmacist Peretta, who believes that about 10 percent of medications circulating in Argentina are fake or stolen, the real key to fighting these crimes is being able to trace the origin of any suspicious medication. One of the recommendations of the WG/CDC is that regulatory authorities should "have mechanisms and technologies to trace drugs effectively in the different stages of the drug chain (from production to dispensing), including lot numbers in purchase and sale documents (invoice, receipts, etc.)."

The experts also proposed that retail drug sales to the public be limited to pharmacies. "You can't have medications being sold by street vendors," agrees D'Alessio.

At the same time, legislation needs to be updated to address this type of crime. In Argentina, for example, it is not a crime to change the expiration date on a drug unless it is proven that doing so damaged someone's health.


Counterfeit drugs sometimes reach market through legitimate distributors who fail to use the proper controls.

In the 1949 film classic The Third Man, Orson Wells plays an infamous villain who tries to become a millionaire by trafficking in adulterated penicillin. Half a century later, reality has surpassed fiction, and authorities are struggling to reverse what has become a growing global trend.

"This has to be a coordinated effort, because with counterfeit drugs, everyone loses: the industry, patients, health professionals.... The only ones who win are the counterfeiters," D'Alessio complains.

She also believes that regulatory authorities are becoming more aware of the problem, and most are committed to implementing more effective sanctions.

"We can't let down our guard," she warns. "Drug counterfeiters are like a metastatic cancer that attacks in one place and then shows up in another. You can't just catch some of them and punish them and then assume that you're home free."

Matías Loewy writes on science and health for Noticias magazine in Argentina.

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Best Buys for Public Health

HIV: What You Know Can Help You

Deadly Imitations

Genetics in the Service of the People

Health Goes to School

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