WASHINGTON --A contaminated blood thinner from China suspected in dozens of U.S. deaths has now become a worldwide public health problem, with 10 other countries detecting the often-toxic ingredient, federal investigators said yesterday.
The compound, which in tests mimics the real blood thinner heparin but costs less to make, may have been added deliberately somewhere along a production chain that began on farms in China, beyond the reach of U.S. regulators.
Food and Drug Administration officials also announced a major scientific breakthrough in their attempt to understand how patients got sick from the contaminated heparin. In addition, the agency stepped up its enforcement actions against a facility in China that supplied the medication for the U.S. market. And officials raised the possible death toll from 62 to 81.
The rapid developments came on the eve of a congressional hearing expected to show that the FDA lacks the resources to carry out adequate inspection of thousands of foreign facilities now producing a significant share of the medications consumed here.
"Contamination of the heparin supply is a worldwide problem," said Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research. Thus far in the investigation, about a dozen Chinese facilities of varying sizes have been identified as being part of the supply chain that handled contaminated heparin, although it is still unclear where and how the problem began.
Heparin is a widely used blood thinner, given to patients undergoing kidney dialysis or heart surgery to prevent dangerous clots. The ingredient that contaminated the drug, a chemically modified from of a common nutritional supplement, has now been shown in laboratory and animal tests to cause the dangerous reactions that some patients experienced, Woodcock said. These included a sudden drop in blood pressure, leading to shock.
"We have data in the test tube, and animal data, that shows this contamination can trigger events that would lead to these types of reactions," Woodcock told reporters. "That doesn't tell us ... the whole story, but it does establish the link."
Woodcock explained that the contaminant - a compound called an oversulfated chondroitin sulfate - can trigger chemicals in blood cells that produce serious allergic-type reactions.
These chemicals, called blood mediators, are often spurred into action when a wound is opened, helping to generate new blood vessels around the wound and drawing in antibodies to clean up damaged areas, Marilyn Halonen, a pharmacology professor at the University of Arizona, said in an interview.
But blood mediators can also cause a drop in blood pressure and other reactions in patients who receive large doses of contaminated heparin.
"If this compound is getting to a lot of cells at once, it's causing a mediator storm," said Halonen. The FDA's Woodcock said the dangerous reactions seen in U.S. patients and some in Germany may be linked to large intravenous doses of contaminated heparin.
"It does appear that the route of administration, the amount and how fast it's administered, may play a role," she said.
Chinese officials, however, have remained skeptical of such a link. At a Chinese Embassy news conference yesterday, senior public health officials said they doubted the evidence linking the contaminant to serious side effects. Instead, they urged a look at the U.S. facilities of Baxter Healthcare Corp., the Illinois-based company that imported heparin from China and distributed it here.
The FDA and Baxter have maintained that the source of the problem lies in China.
Heparin is produced from a naturally occurring substance found in the lining of pigs' intestines, and the process involves several layers of middlemen and suppliers. The contaminant could have been added to make the drug seem more potent, or it could have been introduced accidentally by some misstep in production .
Yesterday, the FDA cited Baxter's supplier in China for "significant deviations" from U.S. manufacturing practices. That supplier, Changzhou SPL, is a joint venture company partly owned by Wisconsin-based Scientific Protein Laboratories.
In a warning letter to the company, the FDA said it found problems with the process for removing impurities from heparin, and also with the company's system for evaluating its suppliers. SPL responded with a statement saying many of the concerns the FDA cited have already been corrected. But the agency says it will require more proof before the Changzhou plant is allowed to export to the United States again.
Because of a mixup over names at the FDA, that plant was never inspected before it started exporting to the United States. Rep. Bart Stupak, (D-Mich.) who is pushing import safety legislation, said the heparin episode has revealed major weaknesses in the FDA's oversight of foreign companies.
"No one is watching the cooks in the kitchen," Stupak said. "This is serious, and I don't think the FDA can address it based on its current structure and its lack of resources."
However, Health and Human Services Sec. Mike Leavitt said in an interview that the U.S. and Chinese governments are making good progress in improving product safety standards for Chinese imports. The FDA hopes to place an inspector in China by the fall.
RICARDO ALONSO- ZALDIVAR WRITES FOR THE LOS ANGELES TIMES