New USP standards for heparin products will result in decreased potency

The US Food and Drug Administration has alerted health care professionals to a change in heparin manufacturing that is expected to decrease the potency of the common anti-clotting drug, meaning that adjustments may be needed to achieve desired anticoagulant effect in some patients.

To ensure the quality of heparin and to guard against potential contamination, the United States Pharmacopeia (USP), a non-profit standards-setting organization, adopted new manufacturing controls for heparin. These changes include a modification of the reference standard for the drug's unit dose.

Manufacturers in the USA label the amount of heparin included in their products based on USP standards. The changes adopted by the USP for the heparin unit dose match the World Health Organization's International Standard (IS) unit dose definition that has been in use in Europe for many years. The revised USP reference standard and unit definition for heparin is about 10% less potent than the former USP unit.

Manufacturers for the US market have begun to make heparin using the new USP standard. While the USP manufacturing controls take effect October 1 for production, the FDA has asked that they not ship this new product to customers until October 8, or later. The delay will give health care providers and facilities time to learn about the changes and to make adjustments to their pharmacy procedures and dosing practices, according to John Jenkins, Director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research.

'Although the FDA-approved labeling for heparin has not changed, including the recommended doses, it is essential that health care professionals be aware of the potential difference in potency between the old and new vials of heparin when administering the drug,' said Dr Jenkins. 

Four companies market heparin in the USA. APP, the largest manufacturer, markets heparin in vials; Hospira does so in intravenous bags, vials and syringes; Baxter markets heparin in intravenous bags, and B Braun in intravenous bags. The FDA has asked that all manufacturers identify their new products to help pharmacies and health care professionals differentiate it from the former product.

The monograph was revised, in part, in response to a 2007-2008 incident of heparin contamination involving a manufacturing step in China, which was associated with deaths and other adverse events in the USA. The monograph was changed to include a test for the contaminant.