A compound related to a common nutritional supplement has been identified as the contaminant in a blood-thinning drug imported from China that sickened hundreds of frail patients in the U.S. and is suspected in a number of deaths, federal officials said Wednesday.
The substance mimics the real drug -- heparin -- in standard safety tests and may have been deliberately substituted for the genuine compound somewhere along the line to boost middlemen’s profits. It could also have been added through a mishap or some kind of misguided experiment. Because of difficulties in back-checking, it’s unclear whether Food and Drug Administration officials will ever know for sure.
The FDA’s announcement came days after the anniversary of last year’s massive recall of contaminated pet food. In that case, the agency found that a chemical added to pet food ingredients from China had sickened thousands of dogs and cats, many of which died.
The recall inflamed public concerns about the safety of consumer goods from China; the heparin investigation may give a boost to legislation stalled in Congress that would set up a much more rigorous import inspection system.
“It is unacceptable that Americans have died and been seriously injured by what appears to be deliberate tampering,” Sen. Edward M. Kennedy (D-Mass.), who chairs a panel that oversees the FDA, said in a statement. “Whether this contaminant was introduced intentionally or by accident, the full force of the law must be brought to bear to bring those responsible to justice.
“To guard against future abuses, every drug manufacturer needs to inform FDA of where it sources its ingredients and what it is doing to ensure that these ingredients are pure and potent.”
Benjamin L. England, a former FDA lawyer involved in enforcement matters, said there had been past cases in which manufacturers and suppliers used unapproved materials to boost production capacity or to save money.
“This is not a new problem,” said England, who now advises foreign companies on how to comply with U.S. regulations. “This is a close cousin of problems that have presented themselves before.”
The FDA is chronically short of resources to meet its mandate to oversee a vast array of drugs, medical devices, and processed and natural foods. Inspections of foreign producers in particular are infrequent. And China has been difficult territory for U.S. regulators.
Although Chinese facilities account for 22% of the foreign plants supplying drugs to the U.S. market, they received about 6% of the FDA inspections between 2002 and 2007, according to a recent congressional report.
The FDA and the heparin manufacturer, Baxter Healthcare Corp., said sophisticated testing identified the contaminant as hypersulfated chondroitin sulfate.
Chondroitin sulfate, which is made from animal cartilage, is an ingredient in dozens of nutritional supplements marketed to promote healthy joints and to help people trying to cope with arthritis. On a molecular level, it is related to heparin.
However, FDA Deputy Commissioner Janet Woodcock said hypersulfated chondroitin sulfate was “not an approved drug in the United States, nor should it be present in heparin.”
The level of the contaminant ranged from 2% to 50% in lots of heparin tested by the FDA. An agency official said the contaminant was cheaper to produce than heparin, which is refined through a laborious process from a substance in pigs’ intestines.
Heparin is given to patients undergoing heart surgery or kidney dialysis to prevent blood clots that can cause strokes and heart attacks. China has become the world’s leading producer of heparin because of its plentiful supply of pigs and its low labor costs.
Woodcock said the FDA had received no new reports of deaths possibly linked to Baxter’s heparin since the company issued a recall last month. The company and federal authorities are still trying to determine how the contaminant may have caused the severe allergic reactions suffered by patients, including a sudden drop in blood pressure. A cause-and-effect relationship has yet to be scientifically proven.
Illinois-based Baxter said it believed the contaminant was introduced into the supply chain before raw heparin reached its supplier, Scientific Protein Laboratories. The Wisconsin-based supplier is a joint-venture partner in the Changzhou, China, facility that supplied the tainted heparin to Baxter.
Both companies think the contamination occurred before the heparin reached the Changzhou plant. That facility is supplied by three “consolidators” who process raw material from other suppliers, including slaughterhouses.
FDA officials stopped short of calling it a case of pharmaceutical counterfeiting, although such scams are on the rise worldwide.
“We cannot rule whether this is accidentally or deliberately added,” Woodcock said. “We are 99% sure it is not a natural component.”
She added: “It didn’t come straight from the pig. That would be very improbable.”
Some independent experts said tampering seemed to be the most likely explanation.
“If I had to guess, I would say this is a lot like the pet food case,” said Larry D. Sasich, chairman of pharmacy practice at the LECOM School of Pharmacy in Erie, Pa. “This sounds like somebody in China figured out a way to make the active ingredient look or test like heparin when it was not.”
Legislation introduced by Rep. John D. Dingell (D-Mich.) would set up a much more stringent system to oversee imports. But it’s unclear whether the Bush administration will support Dingell’s proposal, which would be financed through new industry fees.
FDA officials said that recent agreements between the U.S. and China resulted in far greater cooperation from Chinese authorities in the heparin case than the agency received in the pet food case. This time, China expedited visas for FDA investigators, who are being assisted by their Chinese counterparts as they try to trace the source of the problem back through the supply chain.