USP Issues New Quality Standards for Heparin

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ePT--the Electronic Newsletter of Pharmaceutical Technology

The US Food and Drug Administration issued an alert to healthcare professionals of a change in heparin manufacturing that is expected to decrease the drug's potency.

The US Food and Drug Administration issued an alert to healthcare professionals of a change in heparin manufacturing that is expected to decrease the drug’s potency. The change is a result of a second round of revised quality standards and controls for manufacturing heparin issued by the United States Pharmacopeia (USP), effective Oct. 1, 2009.

USP started initial revisions for quality standards for heparin in 2008 after adverse reactions and deaths resulted from heparin intentionally adulterated with oversulfated chondroitin sulfate. The first stage of the quality revisions were released by USP in June 2008, and USP continued to work on modernizing the existing heparin monograph. The second-stage tests and accompanying reference materials that enable manufacturers to compare their products to a proven standard were first announced by USP in February 2009. Following a period of public comment, the standards are now enforceable in the US by FDA, according to an USP press release.

As part of the second-stage revisions, USP harmonized dosage measurement units with those established by the World Health Organization (WHO). The changes adopted by USP for the heparin unit dose match WHO’s International Standard (IS) unit dose definition that has been in use in Europe for many years, according to FDA. The revised USP reference standard and unit definition for heparin is about 10% less potent than the former USP unit, according to FDA. Manufacturers in the United States label the amount of heparin included in their products based on USP standards. A unit is the measure of a drug’s activity in the body. For heparin, a unit dose is the measure of the drug’s ability to block the blood’s natural clotting ability (anticoagulation). Heparin’s potency is determined by the dose of the drug required to produce a specific level of anticoagulation.

Although the USP manufacturing controls take effect Oct. 1 for production, FDA has asked manufacturers to not ship this new product to customers until Oct. 8, 2009, or later. The delay will give healthcare 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 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 healthcare professionals be aware of the potential difference in potency between the old and new vials of heparin when administering the drug,” said Jenkins in the FDA release. To give manufacturers and practitioners the opportunity to understand the revisions, FDA and industry will conduct communications outreach to clinicians and hospitals. 


Four companies market heparin in the United States, according to FDA: APP Pharmaceutical (Schaumburg, IL), Hospira (Lake Forest, IL),  Baxter International (Deerfield, IL), and B. Braun (Bethlehem, PA).

USP and FDA are now starting work on a third stage of revisions to the heparin standards, which will involve laboratory research designed to provide greater sensitivity and precision to the tests and standards used to help ensure drug quality, according to the USP release.

Read further information on USP’s revisions to quality standards for heparin.