FDA tracked tainted drugs, but trail went cold in China
By Walt Bogdanich
Sunday, June 17, 2007
After a drug ingredient from China killed dozens of Haitian children a decade ago, a senior American health official sent a cable to her investigators: Find out who made the poisonous ingredient and why a state-owned company in China exported it as safe, pharmaceutical-grade glycerin.
The Chinese were of little help. Requests to find the manufacturer were ignored. Business records were withheld or destroyed.
The Americans had reason for alarm. "The U.S. imports a lot of Chinese glycerin, and it is used in ingested products such as toothpaste," Mary Pendergast, then deputy commissioner for the Food and Drug Administration, wrote on Oct. 27, 1997. Learning how diethylene glycol, a syrupy poison used in some antifreeze, ended up in Haitian fever medicine might "prevent this tragedy from happening again," she wrote.
The agency’s mission ultimately failed. By the time an FDA agent visited the suspected manufacturer, the plant was shut down and Chinese companies said they bore no responsibility for the mass poisoning.
Ten years later it happened again, this time in Panama.
Chinese-made diethylene glycol, masquerading as its more expensive chemical cousin glycerin, was mixed into medicine, killing at least 100 people there last year. And recently, Chinese toothpaste containing diethylene glycol was found in the United States and seven other countries, prompting tens of thousands of tubes to be recalled.
The agency’s efforts to investigate the Haiti poisonings, documented in internal FDA memorandums obtained by The New York Times, demonstrate not only the intransigence of Chinese officials, but also the same regulatory failings that allowed a virtually identical poisoning to occur 10 years later. The cases further illustrate what happens when nations fail to police the global pipeline of pharmaceutical ingredients.
In Haiti and Panama, the poison was traced to Chinese chemical companies not certified to make pharmaceutical ingredients.
State-owned exporters then shipped the toxic syrup to European traders, who resold it without identifying the previous owner - an attempt to keep buyers from bypassing them on future orders.
As a result, most of the buyers did not know that the ingredient came from China, known for producing counterfeit products, nor did they show much interest in finding out.
China itself was a victim of diethylene glycol poisoning last year when at least 18 people died after ingesting poisonous medicine made there. In the wake of the deaths, and reports of pet food and other products contaminated with dangerous ingredients from China, officials there announced that they would overhaul the regulation of food, drugs and chemicals.
Beyond the three incidents linked to Chinese diethylene glycol, there have been at least five other mass poisonings involving the mislabeled chemical in the past two decades - in Bangladesh, Nigeria, Argentina and twice in India.
"This problem keeps coming back," said Joshua Schier, a toxicologist with the Centers for Disease Control and Prevention. And no wonder: the counterfeiters are rarely identified, much less prosecuted.
Finding a way to keep diethylene glycol out of medicine, particularly in developing countries, has confounded health officials for decades. "It is preventable, and we have to figure out some way of stopping this from happening again," said Carol Rubin, a senior Centers for Disease Control and Prevention official.
In a global economy, ingredients for drugs are often bought and sold many times in different countries, sometimes without proper paperwork, all of which increases the risk of fraud, the authorities say.
The Panama poison passed through five hands, the Haitian poison six. In both instances, the factory’s original certificate of analysis, attesting to the contents of the shipment and its provenance, did not accompany the product as it moved around the world.
"Where there is a loophole in the system, a frailty in the system, it’s the ability of an unscrupulous distributor to take industrial or technical material and pass it off as pharmaceutical grade," said Kevin McGlue, a board member of the International Pharmaceutical Excipients Council.
Uncovering that deception can be difficult. "It’s impossible to get anyone to do the trace-backs," said Michael Bennish, co-author of a 1995 medical journal article on a poisoning epidemic in Bangladesh.
One reason, Bennish said, is the clout of local manufacturers. "We tried to follow up as amateur Sherlocks, investigators, but you don’t go down to the wholesale market and ask questions," he said. "You are going to get your fingers burnt."
The United States may not have gotten what it wanted from China, but the Haiti crisis did bring together health groups to search for ways to stop diethylene glycol poisonings. At a workshop in Washington in February 1997, health experts recommended that certificates of analysis be improved to allow users to "trace the product back through every intermediary, broker and repackager to the original manufacturer."
The workshop participants also called for better testing of drug ingredients and asked governments to tighten oversight of drug manufacturing.
The next year, the World Health Organization offered many of the same recommendations. And a 1998 article in JAMA, The Journal of the American Medical Association, warned that failure to strictly follow the guidelines could cause poisonings "even in countries where quality control procedures are usually strictly applied."
Much of this had been said before, yet the poisonings have continued.
Just as the JAMA article was being published, three dozen children began dying of acute renal failure at two hospitals in Delhi. A local drug maker had unwittingly mixed diethylene glycol into acetaminophen syrup, much as the Haitian pharmacist had.
The drug maker was prosecuted, but according to interviews and government records no progress had been made in identifying the poison supplier.
"My experience as an investigator tells me that many of these things will not be proven," said M. Venkateswarlu, the drug controller general of India.
Finding counterfeiters often means pursuing leads across foreign borders, and no international authority has the power to do that.
Howard Zucker, who helps to oversee drug issues for the WHO, said individual countries must conduct their own trace-back investigations.
David Mishael, a Miami lawyer, knows the difficulty of assigning blame in these deaths. For 10 years, Mishael has unsuccessfully pursued legal claims in the United States and Europe against European traders who helped to arrange the shipment of toxic syrup to Haiti.
"You can imagine the cost," said Mishael, who is representing Haitian parents whose children died from the fever medicine.
He said the authorities in the Netherlands assessed a $250,000 fine against the Dutch company Vos, which tested the counterfeit syrup, found it impure and did not alert anyone in Haiti. But given how many died, he called the size of the fine "a joke." A lawyer who represents Vos, Jeffrey Shapiro, declined to comment.
A few children survived after being flown to the United States by humanitarian groups. One of them, Faika Jean, was 2 months old at the time and nearly died en route. Now 11, she has learning disabilities as a result of the poisoning, said her father, Wislin Jean.
Pendergast, now a private lawyer and consultant, said China had the most to answer for. "Everybody else is just reacting to initial failures," she said. "It needs to take steps to protect not just its own consumers but also consumers all around the world."
After it was reported in May that the Panama poison had been made and exported by Chinese companies as 99.5 percent pure glycerin, Chinese regulators said they would reopen their investigation of the incident. Three weeks later, the officials acknowledged some "misconduct" in how Chinese companies labeled the toxic syrup.
But most of the blame, they said, rested with a Panamanian importer who changed the paperwork to make the syrup look safer than it actually was.
The FDA disagrees, saying the deception began with Chinese companies falsely labeling a poisonous product glycerin. "If the drums had been 99.5 percent glycerin, the deaths in Panama would never have occurred," the agency said.
Reporting was contributed by Jake Hooker from Beijing, Hari Kumar from New Delhi, Anand Giridharadas from Mumbai, and Julfikar Ali Manik from Dhaka, Bangladesh
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