FDA spells out its expectations for crude heparin

If API manufacturers and drugmakers had any doubt about how the FDA wants them to treat crude heparin, it is settled now. The FDA has issued final guidance that spells it out so that there will be no repeat of the problems 5 years ago when dozens of Americans died because of contaminated products.

As Regulatory Focus reports, the new guidance says manufacturers should:

- test the heparin to determine the "species origin" to make sure the ingredient comes only from pig intestines;

- test all heparin lots for over-sulfated chondroitin sulfate (OSCS) or or non-porcine ruminant material contaminants;

- audit heparin suppliers on a regular basis to make sure they are following standards;

- test for and reject any lots that contain other ruminant mucosa.

As the guidance points out, in 2008, the FDA started getting reports that patients on dialysis taking heparin were having severe hypersensitivity reactions. The agency says 10 other countries were also reporting problems. The FDA tracked the problem back to crude heparin from China, the largest supplier to heparin manufacturers, which contained OSCS. The agency found Chinese suppliers intentionally used oversulfated chondroitin sulfate because it was cheaper. "OSCS contamination of heparin appears to be an example of intentional adulteration, and has also been referred to as economically motivated adulteration," the agency said last year. Since then the FDA has banned supplies from 22 Chinese companies.

The agency also recommends that manufacturers test for bovine spongiform encephalopathy (BSE), which could result when non-pig ingredients are substituted. BSE is also known as mad cow disease. Given the fact that there have been bad players identified in the past, the FDA says "it is important for drug and medical device manufacturers to be diligent in ensuring that no component used in the manufacture of any drug or medical device containing heparin is contaminated with OSCS or non-porcine material."

- here's the guidance (PDF)
- read the Regulatory Focus story