FDA widens probe in Heparin deaths

WASHINGTON — WASHINGTON -- Renewing fears about unsafe Chinese products, investigators probing deaths linked to a popular blood thinner are trying to determine whether the drug was deliberately contaminated in China with a fake ingredient.

Testing of the suspect Heparin products revealed significant quantities of a chemical that looks like the key ingredient in the drug and apparently substituted for it, federal drug regulators said yesterday.


All of the ingredient came from China, the drug's maker said. Investigators are exploring how the copycat got into the blood thinner and whether it was introduced in China.



"We do not know if this occurred by some error or by some biological process or occurred deliberately," said Dr. Janet Woodcock, the Federal Drug Administration's deputy commissioner. She said "it is possible" that the substitute was used for fraudulent reasons.

The contaminated drug might be responsible for as many 19 deaths and hundreds of severe allergic reactions, Woodcock said.

Baxter International Inc. sold 100,000 doses of Heparin a year until the serious side effects began surfacing. Several of its batches were recalled Jan. 17, and the withdrawal expanded Feb. 28 to include virtually all of Baxter's other Heparin products.

Investigators have yet to pinpoint a cause but have focused on its production, especially the manufacture of the key ingredient at a plant in eastern China.

Word that as much as 20 percent of the key ingredient in suspect batches came from a substitute revived concerns about the integrity of Chinese suppliers. Those fears first arose last year, after investigators asserted that Chinese suppliers of a major pet food ingredient spiked shipments with the cheap chemical melamine to boost the value.

Routine testing failed to detect that the chemical wasn't Heparin, Woodcock said. Investigators only found the contaminant after conducting special tests.

"It was a classic chemistry investigation," she said.

Investigators still don't know what the look-alike is or whether it caused the deaths, rapid heart rates and other side effects.


Baxter officials, who also are investigating, said all signs point to the Heparin-like chemical being at fault.

"I believe it is the root cause, " said Peter Arduini, president of Baxter's Medication Delivery business.

Rep. Bart Stupak, a Michigan Democrat who is leading a congressional investigation into FDA monitoring of several products, including Heparin, expressed concern that "this is melamine all over again."

"Is this China once again trying to cut corners?" he asked. "Is it a race to the bottom jeopardizing patient safety?"

Unlike the many drugs fashioned in laboratories from simple molecules, Heparin is built out of a complicated chemical derived from crushed pig intestines. Its natural sourcing means more opportunities for impurities to enter the product.

Baxter International, of Deerfield, Ill., bought the pig-derived ingredient from Scientific Protein Laboratories. That company - owned by American Capital Strategies, a buyout firm in Bethesda - made the ingredient at a plant it co-owned in Changzhou, China.


Scientific Protein Laboratories then processed the raw material from China at its facility in Waunakee, Wis. FDA and Baxter officials said the contamination could have taken place in China or Wisconsin.

Given that all of the tainted ingredient came from China, it would be natural to focus on whether the contamination took place at the Changzhou plant or its in-country suppliers, Arduini said.

Problems at plant

An FDA investigation found problems at the Chinese plant, including flaws in its quality control procedures and its processes for removing impurities.

Scientific Protein Laboratories issued a statement dismissing speculation about the cause as unfounded.

"We don't know what it is, but there's no evidence whatsoever pointing in the direction of the notion that it's counterfeiting or something like that," said Wayne Pines, a company spokesman.


Heparin is commonly used in dialysis treatment and heart procedures. With the Baxter recalls, another Heparin maker, APP Pharmaceuticals of Schaumburg, Ill., has stepped up production to meet demand.