WASHINGTON—U.S. regulators on Wednesday said they identified a contaminant in the key ingredient in Baxter International's recalled blood-thinning drug heparin amid 15 more reports of deaths in patients treated with some version of the drug.
The contaminant, a large complex molecule chemically similar to heparin, was detected in samples from a Chinese and a U.S. plant, both owned by Baxter's supplier, Wisconsin-based Scientific Protein Laboratories LLC (SPL).
"At this point we don't know how the heparin-like compound got into the active pharmaceutical ingredient," Food and Drug Administration Deputy Commissioner Janet Woodcock told reporters on a conference call. "We don't yet have a direct causal link between the contaminant and the adverse events."
Heparin is derived from pig intestines and is used in dialysis and heart procedures, among other surgeries, to avoid blood clots. About 200,000 doses are given a day in the U.S., according to Baxter, which supplied about half of that before its recall of virtually all its heparin products last week.
The FDA said 19 deaths have been reported in patients taking a version of heparin that appears related to the drug, though it is unknown if all of those patients were on Baxter's heparin or another company's product. Some of the deaths date back to January 2007.
The other major U.S. heparin supplier, APP Pharmaceuticals Inc, ramped up production to avoid a drug shortage. Tests on APP's heparin have not turned up any contamination, Woodcock said.
Both FDA and Baxter officials said it is unclear whether the contaminant was added intentionally or if it occurred as part of a natural biological process.
"We still don't know whether this inadvertently got into the supply or whether it was actually added" deliberately, Woodcock said.
Baxter officials said they believe only four deaths have been definitely linked with their product. It has received about 500 reports of severe reactions, compared to FDA's 785 reports, which the agency said it has not fully reviewed yet.
"We are having information emerge literally every hour almost on this situation," Woodcock said.
Tainted Products From China
The FDA's foreign inspection process has been criticized for years as inadequate and those complaints were stoked when FDA officials acknowledged recently the agency never inspected the Chinese plant in question because of confusion over the company's Chinese name.
The agency inspects about 7 percent of foreign manufacturing facilities annually, according to the Government Accountability Office, a congressional watchdog agency.
Woodcock and Baxter both cautioned that increased attention to the problem has led to an influx of side-effect reporting and that many cases may not be related to the drug.
The Deerfield, Illinois-based company gets a small portion of its revenue from heparin, which is available in generic form and has been on the market for decades.
Baxter estimated recent annual sales of its Heparin at about $30 million. Baxter had total sales of $3 billion in the fourth quarter.
China Link
Most of the world's crude heparin comes from China, which has become a major supplier of raw ingredients to pharmaceutical companies. All the raw material for Baxter's product came from China as well.
Baxter released a chart showing the product's development cycle from pig farms, to slaughterhouses, to consolidators, to the Chinese and U.S. manufacturing plants under review. The product is finalized at Baxter's Cherry Hill, New Jersey facility.
Last week, the FDA said it found "objectionable conditions" at the Chinese plant that supplied the raw ingredient. Facility owner Scientific Protein Labs in a statement said the contaminant theory is "speculation at this point" and that it is working with the FDA to determine the cause of the problems.
Baxter said SPL is responsible for tracking the supply chain down to the farms where the pigs are raised.
"They've told us they can trace to the pig level," a Baxter official said.
Severe reactions such as anaphylaxis and low blood pressure are signs of dangerous allergic reactions related to heparin use.
Baxter has ruled out its Cherry Hill facility as a source of the problem.
