In response to the heparin contamination and resulting deaths, the FDA asked the United States Pharmacopeia (USP) on March 19, 2008 to assist in re-assessing current tests and developing new methods for detecting contaminants, such as over-sulfated chondroitin sulfate, in heparin. (See 04/14/08 USP Press Release.) The USP is an independent, science-based public health organization that sets the official public standards for all prescription and over-the-counter medicines, dietary supplements, and other healthcare products manufactured and sold in the United States. (To learn what a “pharmacopeia” is, click here. To learn more about the USP itself, click here.)

Among other functions, the USP plays a critical role in developing “monographs” for drug substances, drug products, or “excipients,” (substances that act as a vehicle for a drug). A monograph is a written standard that describes the medical drug, device or product and provides a public standard by which to judge its quality or to test it in order to produce a high-quality and consistent product. (See July 2004 USP Monograph Backgrounder for more information.) These monographs may be updated. For example, heparin, which has been sold in the United States since the 1940s, has had a USP monograph since 1950 that has been updated several times. (04/14/08 USP Press Release.)

Monographs are published in the National Formulary (USP-NF), which was originally created in 1888 and contains more than 4,000 monographs for prescription and over-the-counter products, dietary supplements, medical devices and other health care products. (Feb. 2005 USP Program, “What is a Pharmacopeia?”) When a standard is published in the USP-NF, federal and state government agencies, such as the FDA, can recognize and enforce those standards to ensure product compliance and quality. Currently, there are monographs for two heparin drug substances in the USP-NF. (04/11/08 USP Heparin Statement.)

In April of 2008, the USP started working to develop more sensitive methods for detecting contaminants found in heparin. (04/14/08 USP Press Release.) This work was divided into two stages. Stage one would include revisions to the heparin monographs, and was “intended to address rapidly the immediate public health crisis associated with the drug and help ensure an unadulterated supply of heparin.” (06/23/08 USP Press Release.) The second stage would seek additional methods to test for over-sulfated chondroitin and other potential contaminants in heparin.

The USP conducted a “heparin web meeting with the industry” on April 11, 2008. (To view the power point presentation for that meeting, click here.) On April 25, 2008, the USP’s Heparin Advisory Panel provided written recommendations for the revision of the heparin sodium monograph. (To view these recommendations, click here.) An open microphone meeting regarding the recommendations was then held on June 11, 2008. (To view the agenda for this meeting click here. To view the presentation given at this meeting click here.)

As a result of these meetings and recommendations, on June 23, 2008, the USP announced that stage one had been completed and that the monographs for heparin sodium and heparin calcium had been revised and are now available on the USP Web site. (06/23/08 USP Press Release.) The two heparin monographs are posted on the USP Web site at http://www.usp.org/hottopics/heparin.html?hlc. These revised monographs are accompanied by new and updated official USP Reference Standards, that all drug manufacturers who market heparin in the United States are required to meet. (For additional information, see USP “Heparin Monograph Revision Frequently Asked Questions.”)

The USP indicates that it will now turn to “the second stage of revision,” which involves seeking out additional methods to test for over-sulfated chondroitin and other potential contaminants in heparin. (06/23/08 USP Press Release.)

Although these revisions are important and the USP should be thanked for its hard work, as recognized by the USP itself, they are only “one of a series of safety nets that work to assure that U.S. patients and practitioners have access to good quality medicines.” (Statement of USP executive vice president and CEO, Roger L. Williams, M.D., in the 06/23/08 USP Press Release.) These other critical safety nets must also include “dedicated and trusted drug ingredient and product manufacturers who follow good manufacturing practices (GMPs) and sound sampling protocols in support of batch release testing,” and “oversight from the FDA...” (04/14/08 USP Press Release.)

As we have unfortunately now learned from the heparin disaster, when these other safety nets are not in place, the ramifications can be devastating. Companies who do not use good manufacturing practices or purchase product from companies who do not use good manufacturing practices, and do not adequately test their drugs, should be held accountable when those defective drugs cause death and injury. At the same time, the FDA must be given the resources and power it needs to enforce compliance by powerful and wealthy drug companies, including those who want to save money by purchasing product from uninspected and substandard plants in foreign countries.