New Heparin Standards Reduce Potency of Drug 10%


October 02, 2009

October 2, 2009 (Rockville, Maryland) — Manufacturers of heparin will begin rolling out a product next week that is roughly 10% less potent than the heparin currently available, and the Food and Drug Administration is asking clinicians to be aware of the change, particularly in situations where the drug is administered as an intravenous bolus.

The heparin reformulation is the result of manufacturing controls occurring in the wake of the 2007 and 2008 contaminations that were linked to deaths and allergic reactions and was proposed by the US Pharmacopeia (USP), a nonprofit standards-setting organization. The USP monograph change includes a modification in the reference standard for the drug’s unit dose. The change in the heparin unit dose now matches the World Health Organization International Standard (IS) unit dose definition, one that is currently in use in Europe.

During a briefing with the media, Dr John Jenkins, FDA director of the Office of New Drugs, said that the current FDA-approved labeling for heparin has not changed, including the recommended doses, but that clinicians need to be aware of the reduced potency when administering heparin in settings where an immediate anticoagulant effect is clinically important.

"The individualization of heparin dosing has long been the standard for clinical use with the drug, and the FDA reiterates the importance of clinical judgment in heparin dosing as we implement the new USP monograph," said Jenkins.

The agency learned just three weeks ago that the changes in the reference standard, which have been in the works for months, would affect potency. Jenkins said that the agency does not currently have data to assess the clinical impact of the potency change and for that reason can't make specific dosing recommendations. It is currently working with the manufacturers on in vitro and animal studies to better understand the issue, he said.

The USP manufacturing controls took effect October 1, 2009 for production, but the new product will not be shipped until October 8, 2009. The FDA points out there will be periods of overlap when both the old and new heparin is available. There are four companies that market heparin in the US: APP, the largest manufacturer, Hospira, Baxter, and B Braun. Three of the four companies will include the letter N on their product to identify the heparin with the new reference standard, while Hospira will identify the changed product with a numeric code.

In addition to the new reference standard, the change in the monograph includes a new test method, which, unlike the previous method, is able to detect impurities that may be present in heparin.