BioEd Online

In the ongoing fight against dangerous counterfeit pharmaceuticals, one partial success story is highlighted in PLoS Medicine this week¹. The report showcases how an international collaboration among researchers and law-enforcement officials led to the arrest of distributors in a counterfeit drug ring in China.

Fake drugs are a huge problem in Southeast Asia; a 2006 review estimated that perhaps half of the medicine sold there is counterfeit². Tablets sold as the malaria-fighting artemisinin may contain only trace amounts of the drug, if any at all. The World Health Organization was so worried by the trend that it launched an International Medical Products Anti-Counterfeiting Taskforce (IMPACT) in early 2006.

But even before then, some scientists were taking action. In 2005, Paul Newton, a tropical infectious-disease specialist at the University of Oxford, UK, and others formed a collaboration to use forensics to track the producers of fake malaria drugs.

The collaboration was the first of its kind to harness researchers from around the globe in a public hunt for counterfeit-drug distributors, Newton says. Most previous attempts have been undertaken by pharmaceutical companies, which hired private investigators and kept their investigations secret, says Newton. It is also the first investigation to use the analysis of pollen grains on or in the tablets to track the origin of counterfeit drugs.

Most of the researchers involved in the investigation had no specific funding for the project, Newton notes. “They all did it out of concern and interest,” he says.

Drug hunt

The researchers investigated 391 samples of artesunate collected from Vietnam, Cambodia, Laos, Myanmar, and the border between Thailand and Myanmar.

Chemical analysis revealed that 61% of the drugs were counterfeit. These tablets contained a troubling assortment of chemicals, including potentially dangerous compounds such as benzene and safrole, both classified as carcinogens, and the latter is a precursor of the illicit drug ecstasy.

Some tablets contained a coating of artesunate, the active ingredient in artemisinin, on the outside of the tablet, suggested that they had been pressed in a machine used for making authentic artemisinin. That was one clue as to the pills' origins. And the mixture of chemical isotopes present in the tablets showed that some contained a characteristic type of calcite mined in China near the border with Vietnam.

Dallas Mildenhall, a forensic scientist at Institute of Geological and Nuclear Sciences in Lower Hutt, New Zealand, followed the trail of another clue: pollen in the pills.

Although Mildenhall had used palynology — pollen analysis — to track illicit drugs before, he was not sure how well the procedure would translate to counterfeit pharmaceuticals. Illicit drugs are often loaded with contaminating pollen, but most pharmaceuticals are produced in sterile environments with very little chance for pollen to become mixed in with the tablets, he thought. Nonetheless he found a big difference: counterfeit drugs were comparatively loaded with pollen, with as many as 30-40 pollen grains per tablet. Some of that pollen came from hickory and walnut trees characteristic of southern China.

Final chase

Newton and his colleagues took their evidence to Chinese authorities in 2006. They eventually arrested a native of Yunnan Province who stands accused of purchasing 240,000 blister packs of counterfeit artesunate from a native of Guangdong Province, but have yet to find the producer. “’Mr. Big’, as far as I’m aware, has not been caught yet,” says Newton.

Meanwhile, the researchers have procured some short-term funding and plan to continue their hunt for counterfeit drugs. For Mildenhall, the years he spent conducting research in Southeast Asia left him with a sense of responsibility to the region. “I used to live in Asia, my son has spent most of his life in Asia, and a lot of my friends are Asian," says Mildenhall. “So we had a moral responsibility to do this sort of work.”

In the meantime, IMPACT and others continue to try to stamp down the fake drug trade. International programs like these are useful, says Souly Phanouvong of United States Pharmacopeia, a non-profit company in Rockville, Maryland that helps to provide standards for drug testing schemes. But more could be done, he adds, such as strengthening the capacity of law enforcement within affected countries. “Right now, there are different levels of effort in different parts of the world,” says Phanouvong.