FDA cites Chinese firm's manufacturing processes for heparin
WASHINGTON -- For the Chinese, seeing is believing.
For now, they are rejecting U.S. findings that a contaminant in the blood thinner heparin was introduced in China and is linked to severe allergic reactions that caused up to 81 deaths.
They're seeking heparin samples from Baxter International's Cherry Hill, N.J., plant as part of their own investigation into the heparin problems.
"When you see it, then you believe it," said Jin Shaohong, the deputy director general for the National Institute for the Control of Pharmaceutical and Biological Products in China.
Federal health officials have run their own tests on the suspect heparin and found what they say is a solid link between the contaminant and the allergic reactions that have been reported.
China said the contaminant could not be the "root cause" of the problem.
Raw heparin is derived from pig intestines, often processed by small, unregistered workshops in China. The raw ingredient for Deerfield-based Baxter's recalled heparin came from Wisconsin-based Scientific Protein Laboratories, which in turn owns a Chinese factory _ Changzhou SPL _ and buys additional raw heparin from other Chinese suppliers.
The Food and Drug Administration warned Changzhou SPL on Monday that the company does not have adequate systems for ensuring that the raw materials it uses are safe and that any impurities are removed.
The FDA noted that as many as 12 companies in China are involved in the supply chain for heparin. Agency officials don't know at what point the contaminant was introduced.
Hundreds of patients have suffered severe allergic reactions to large doses of the blood thinner. The FDA said it suspects the problems stem from a compound derived from animal cartilage that so closely mimics heparin that routine purity tests can't detect it.
"We have data in the test tube as well as animal data that shows this contaminant can trigger events that would lead to these type of reactions," said Janet Woodcock, director of the Food and Drug Administration's Center for Drug Evaluation and Research. "That doesn't tell us the whole story. But it establishes a link."
Chinese officials claimed that adverse events were reported in patients who got heparin even when the blood thinner did not contain the contaminant _ over-sulfated chondroitin. But FDA officials said that premise is incorrect.
Chinese exports have been under increasing scrutiny since problems have surfaced with pet food, toothpaste and fish. Millions of Chinese toys have been recalled because they contained lead. Health and Human Services Secretary Mike Leavitt said Monday that in the end, he would be surprised if China did not take strong action to ensure safe heparin ingredients.
Woodcock said the FDA scientists would try to meet with Chinese colleagues in the next few weeks to present their findings.
In its warning letter to the Chinese company, FDA said it will recommend disapproval of any new applications listing the company as the manufacturer of any active pharmaceutical ingredient. It cited "significant deviations" from good manufacturing processes.
The company said it regretted FDA's decision and that it did not believe the warning letter reflected Changzhou SPL's actual state of compliance with good manufacturing practices.
The company said the suspect contaminant was not introduced in the manufacturing processes at Changzhou SPL.
"It is now clear that the suspect contaminant was introduced earlier in the supply chain in China and was widespread throughout the unrelated Chinese supply chains of many companies," Scientific Protein Laboratories said in a news release.
Baxter International officials also took issue with the Chinese claim that the contaminant cannot be a "suspected root cause of heparin adverse events as reported in U.S. media previously."
The company said it provided test results to the FDA confirming that Baxter scientists found consistent, prolonged declines in blood pressure resulting from exposure to contaminated heparin.
"These tests show that significant doses of the over-sulfated chondrointin sulfate do induce a rapid loss of blood pressure," said Norbert Riedel, Baxter's corporate vice president and chief scientific officer. "That means that the contaminant, which was introduced at the workshop or consolidator level, before it reached our (active ingredient) supplier and before it reached Baxter, is likely the cause of the increased adverse reactions to the heparin."