Heparin contaminant found

The U.S. Food and Drug Administration found an unidentified contaminant in batches of the active ingredient used in Baxter International Inc.’s recalled blood thinner heparin, as the agency sharply increased its count of the deaths potentially tied to the drug.

The agency said it couldn’t yet identify how the substance got into Baxter’s product and whether its introduction was deliberate. The drug is being investigated after reported bad reactions in hundreds of patients.

FDA officials said 19 fatality reports, up from a previous tally of four, now appear to match the allergic-type and low blood-pressure reactions that have been the main focus of safety concerns. It wasn’t clear how many of the 19 people took the Baxter product. The deaths occurred since Jan. 1, 2007, but the FDA only received the reports in the past three months or so, the agency said.

The updated death count, which is likely to evolve further as the FDA gets new reports and looks into the ones it has, raises questions about whether the safety issues have lingered far longer and had much broader effects than it previously appeared. It also suggests that hospitals and dialysis centers may not have been reporting all deaths to the FDA. Baxter said its concerns were initially sparked by a surge of reaction reports that started in late December. The company suspended production of its multidose heparin on Feb. 11, then recalled that and some other heparin products last week.

Baxter yesterday said it believed four patients had "suffered an allergic-type reaction to heparin that may have contributed" to a fatal outcome. Baxter said its count was based on strict criteria of medical causality. Rival heparin maker APP Pharmaceuticals Inc. said it hasn’t gotten any reports of allergic-type reactions of the type Baxter and the FDA are describing. The agency said it has now received a total of 785 reports of problems in patients who took some form of heparin, though it isn’t clear that these are all related to drug reactions and some may be duplicates.

The FDA said the contaminant was found in the active ingredient from Baxter’s supplier, Scientific Protein Laboratories LLC, and it was present in large quantities.

"We do not know when it was introduced or how it got into these products," said Janet Woodcock, the acting director of the FDA’s drug center. She said the agency hadn’t determined "whether this inadvertently got into the supply or whether it was actually added." Scientific Protein, which has a facility in Waunakee, Wis., and a joint venture in Changzhou, China, said the contaminants were confined to its "most recent production cycle."

FDA officials said there was an "association" between batches with the contaminant and patient reactions, but the agency hasn’t yet concluded there is a direct causal link. It said the source of APP’s active ingredient hadn’t shown a similar contaminant.

Baxter, of Deerfield, Ill., said the questionable heparin had been made from a Chinese raw ingredient. The unknown substance was a "natural or biologic material," and there is currently "nothing to substantiate" a conclusion that it was a counterfeit product, a company spokeswoman said.

Scientific Protein said it is unsure that a contaminant caused the allergic reactions and that "no conclusions have been reached about the root cause." Nevertheless, the company said it is removing from the market any batches of heparin that show contaminants.

(Source: Anna Mathews, Thomas Burton: Wall Street Journal: March 2008)