The Chinese manufacturer of a heparin ingredient does not have adequate systems for ensuring that the raw materials it uses are safe and that any impurities are removed, the Food and Drug Administration told the company Monday.
The FDA released a warning letter to Changzhou SPL Co., hours after Chinese officials voiced doubts that a contaminant identified in the blood thinner heparin caused severe allergic reactions in hundreds of U.S. patients.
The FDA told Changzhou SPL that it had "significant deviations" from good manufacturing processes. Until it complies, the agency will recommend disapproval of any new applications listing the company as the manufacturer of any active pharmaceutical ingredient.
Raw heparin is derived from pig intestines, often processed by small, unregistered workshops in China. Heparin is commonly used before certain types of surgery to prevent dangerous blood clots. Kidney patients also take it before undergoing dialysis.
The raw ingredient for Baxter International'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 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.
At an embassy news conference, Chinese officials said the problems linked to heparin could have occurred in the United States, or that chronic conditions in some patients led to severe reactions. They plan to visit a Baxter International plant in Cherry Hill, N.J., to get a better picture of heparin's development. They also hope to take back some samples for their investigation.
"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.
The FDA has counted 62 deaths from allergic-style reactions that were associated with recalled heparin batches. The FDA can't say for sure what caused the reactions, but the chief suspect is a contaminant that the agency discovered in supplies of raw heparin coming from China — a compound derived from animal cartilage that so closely mimics heparin that routine purity tests can't detect it.
Germany also discovered the contaminant and recalled batches of heparin after some patient illnesses.
But the Chinese officials contended Monday that batches not containing the contaminant — called oversulfated chondroitin — also have been associated with side effects.
"The oversulfated chondroitin can therefore not be a suspected root cause of heparin adverse events as reported in U.S. media previously," Shaohong said.
Baxter denied that claim.
"We do not agree with that," said Baxter spokeswoman Erin Gardiner. "We have seen adverse event reports on batches where the contaminant has been confirmed to be present."
Baxter was considering the Chinese officials' request for additional heparin samples for their own further testing, Gardiner said.
The Chinese officials also said that aside from the U.S. and Germany, more than 10 other countries used heparin containing the contaminant to produce their final injection but reported no side effects. Also, one batch of heparin injections free of the contaminants has resulted in about a hundred adverse events, of which 25 were serious.
The officials also noted that the implicated Chinese factory — Changzhou SPL — was managed and overseen by a manager from its U.S. headquarters. The heparin ingredient produced by the factory has all been exported.
"None has been sold into the Chinese domestic market," Shaohong said.