New USP Standard for Heparin Decreases Unit Dose Potency, Dictates Careful Monitoring

The FDA is alerting physicians about a change in heparin manufacturing that likely will decrease the potency of the widely used anticoagulant by 10 percent.

FDA officials said the U.S. Pharmacopeia, or USP, monograph for heparin has been revised, in part, because of product contamination in 2007 and 2008 that was associated with adverse events, including deaths. The primary changes to the monograph include the implementation of a new USP reference standard and test method that is used to determine the potency of the drug. Unlike the previous test method, the new method is able to detect impurities.

The monograph change synchronizes the USP unit dose with the World Health Organization's International Standard unit dose. The revised USP reference standard for the drug's unit dose definition is about 10 percent less than the previously defined USP unit.

Heparin products that use the new USP unit are expected to be available on or after Oct. 8, but older versions of the drug likely will still be in circulation. Accordingly, the FDA said it has asked manufacturers to label new heparin products in a manner that will help differentiate them from the old products. The agency said labels of most products made according to the new standard will have an "N" that appears in the lot number or after the expiration date. Lot numbers of new heparin products manufactured by Lake Forest, Ill.-based Hospira Inc., one of four companies that market heparin in the United States, will begin with the numerals "82" or higher.

John Jenkins, M.D., director of the office of new drugs in the FDA's Center for Drug Evaluation and Research, said in an Oct. 1 news release that it is essential for physicians to be aware of the potential difference in potency between the old and new versions of heparin, particularly in situations where aggressive anticoagulation is essential to treat or prevent life-threatening thromboses.

The agency also said the potency change may require more frequent or intensive monitoring of patients' activated partial thromboplastin or activated clotting times.