1. Aschenbrenner, Diane S. MS, APRN, BC


* The FDA has alerted health care professionals to changes made in the heparin manufacturing process, one of which is expected to decrease its potency.


* The new manufacturing controls are intended to ensure the quality of the product and prevent contamination.



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The Food and Drug Administration (FDA) has alerted health care professionals to changes made in the heparin manufacturing process, implemented in October 2009, in accordance with revisions to the drug monograph made by the United States Pharmacopeia (USP), an official standards-setting authority for medications and other health care products. The changes have been made in an effort to standardize heparin worldwide, to ensure its quality, and to guard against its possible contamination. The new manufacturing controls include a modification of the reference standard for the drug's unit dose. Heparin manufactured for marketing in the United States customarily has been measured in USP units, whereas heparin manufactured elsewhere has been measured in World Health Organization (WHO) International Standard (IS) units. The revised USP reference standard now matches that of the WHO, and, as a result, the drug is about 10% less potent (necessitating the use of more units to achieve the same therapeutic effect). To differentiate the new products from the old, the FDA has asked manufacturers to include the letter "N" (for "New") in the lot number or after the expiration date in the heparin labeling, with the exception of the manufacturer Hospira, which will use the number "82" (or higher) before the lot number.


The revision to the heparin USP monograph was motivated in part by a 2007-2008 incident in which the use of heparin contaminated during its manufacturing process in China was associated with death and other adverse events in the United States. To prevent contamination, new criteria, including newly required test methods for detection of impurities, have been introduced into the manufacturing specifications.


The FDA-approved heparin labeling and dosage recommendations have not been changed, and the agency is not recommending that all heparin doses be adjusted in light of the change to IS units-titration of heparin to achieve the desired effect in each patient has long been the recommended practice. Although the decrease in the potency of heparin products should not significantly alter their clinical effect, in certain circumstances it could result in a lesser therapeutic effect in the absence of dosage adjustment. For example, the FDA states that the change in potency is expected to be less clinically significant in subcutaneous administration, in which the bioavailability of the drug is low and greatly variable, than in intravenous administration of boluses of heparin for immediate anticoagulative effect. Further studies are being conducted to clarify this, and it is possible that dosage recommendations will change in the future. Nurses should be aware of the present change in the potency of heparin and monitor patients' responses to its administration-dosage adjustments should be made, as appropriate.