Health regulators issued recommendations to ensure the safe production of the blood-clot prevention drug heparin, four years after a contamination involving the widely used product set off concerns about the global pharmaceutical supply chain.
The draft guidance, posted on the website of the Food and Drug Administration on Friday, is designed to help manufacturers of active ingredients, finished products and others better control heparin to avoid contamination.
The FDA began receiving reports in early 2008 of serious reactions, including some deaths, among some patients undergoing
dialysis and traced the problem to heparin, which is injected.
An FDA probe found a contaminant in batches of heparin from Baxter International Inc, a major supplier to the U.S. market, and determined the contaminant was in active ingredients for heparin made in China. The contamination sparked congressional hearings and concerns about the lack of inspections of foreign facilities.
During a recent hearing at the U.S. House of Representatives over user fees paid by the industry, lawmakers urged the FDA to prevent another heparin scare.
"We're making sure we have systems in place to prevent that particular problem," FDA Commissioner Margaret Hamburg told members of Congress last week.
According to the guidance document, contamination involving the chemical at issue - oversulfated chondroitin sulfate (OSCS) - appears intentional to save costs.
"OSCS contamination of heparin appears to be an example of intentional adulteration, and has also been referred to as economically motivated adulteration - i.e., heparin appeared to be intentionally contaminated with OSCS to reduce the cost of production," the agency said in its document.
Heparin is derived from pig intestines and the FDA also said that "substitution of non-porcine sources of crude heparin raises concerns" - in particular materials from cows because of the potential for contamination with material infected with mad-cow disease.
"Both the reported incidents of OSCS contamination and the bovine substitution scenario illustrate the potential for FDA-regulated products derived from heparin to be contaminated," the agency said.
The agency's recommendations included testing for the species origin and the presence of OSCS in each shipment of crude heparin before manufacturing. Heparin manufacturers should also audit their suppliers, the agency said.
Baxter last year sold the U.S. business that included heparin and other generic injected drugs to Hikma Pharmaceuticals Plc. A Baxter spokeswoman said the company has made "significant" changes to its supply chain, including adding safeguards to reduce the risk of adulteration.
Hikma and its U.S. subsidiary, West-Ward Pharmaceuticals, could not be immediately reached for comment. The company has said it makes heparin for the U.S. market only with materials from the United States and Canada, according to its website.
The guidance is a set of recommendations and does not establish legally enforceable responsibilities. FDA will solicit comments on the document for 60 days.
(Reporting By Lewis Krauskopf; additional reporting by Anna Yukhananov; editing by John Wallace, Dave Zimmerman and Andre Grenon)