F.D.A. Tracked Poisoned Drugs, but Trail Went Cold in China

By Walt Bogdanich | The New York Times
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 K. 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 F.D.A.’s mission ultimately failed. By the time an F.D.A. 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 F.D.A.’s efforts to investigate the Haiti poisonings, documented in internal F.D.A. 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 Dr. Joshua G. 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 C.D.C. 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 cases, 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 J. 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 Dr. Michael L. Bennish, co-author of a 1995 medical journal article on a poisoning epidemic in Bangladesh.

One reason, Dr. 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.”

A Crisis in Haiti

By the end of June 1996, the F.D.A. knew it might have an international crisis on its hands. A poison had found its way into fever syrup in Haiti, and the F.D.A. wanted to know if more of the same might be heading to the United States or, for that matter, to any other country. But to learn that, the agency needed to find the manufacturer.

This was not just any poison. Virtually every young poisoning victim who showed up at the main hospital in Port-au-Prince, Haiti’s capital, died.

Labeled pharmaceutical-grade glycerin, the toxic syrup was mixed into thousands of bottles of fever medicine. For months, parents gave it to children, then watched them die, in agony, from kidney failure. No one suspected the medicine until much later.

Officially, at least 88 children died, nearly half under the age of 2. But those 88 were only the ones doctors remembered or for whom hospital records could be found.

The F.D.A. traced the poison to a German broker, Chemical Trading and Consulting, but the company’s records were not much help. “They cannot trace glycerine lots to their manufacturer,” David Pulham, an F.D.A. investigator, wrote on June 30, 1996.

Chemical Trading had arranged for a Dutch company, Vos B.V., to sell 72 barrels of the suspect syrup to Haiti, records show. The agency dispatched an investigator, Ann deMarco, who made an unsettling discovery: sitting in Vos’s warehouse near Rotterdam were 66 more barrels labeled glycerin, all containing lethal concentrations of diethylene glycol.

“Some of this second shipment has been sold,” Ms. deMarco wrote in a memorandum on July 4, 1996. Although the missing barrels had gone to an industrial user, not a drug maker, the F.D.A.’s worries grew.

Ms. deMarco learned that another broker, Metall-Chemie, a German trader, had arranged for Vos to buy the barrels from Sinochem International Chemicals Company, a giant exporter in Beijing owned by the Chinese government.

But Metall-Chemie also did not know the manufacturer, and one of its officials predicted that the F.D.A. would have trouble finding that out. “It is difficult to get any information from Chinese traders,” Ms. deMarco wrote.

>> Read the complete article