Responding to a Crisis: Heparin

A Dire Situation

Nearly 150 people in the United States died in 2007 and 2008, and hundreds suffered serious adverse reactions, after they were treated with heparin—a blood-thinning drug in worldwide use. It turned out to be a tragic object lesson, both in the unintended consequences of a globalized economy and in the life-saving value of collaboration among USP, Food and Drug Administration (FDA), pharmaceutical industry experts, and other countries’ national regulatory agencies. Read More

What happened? While no one is 100 percent certain of the precise cause, it is clear that there were problems with heparin sourced from China. In use since the 1940s, heparin is made from pig intestines. China is home to a large pig population (pork is a diet staple), and is also where a significant portion of the active pharmaceutical ingredients used in the global pharmaceutical industry are made. When widespread pig deaths from “blue ear disease” drove up the price of pig intestines, it appears that over-sulfated chondroitin sulfate (OSCS) was substituted for some of the actual heparin. OSCS costs far less, and was able to “fool” existing quality tests by closely mimicking heparin's blood-thinning characteristics (though it is no substitute for heparin's critical anticoagulant properties). OSCS is a deliberately altered form of chondroitin, legitimately used in dietary supplements. The over-sulfated form can produce reactions such as low blood pressure, abdominal symptoms, shortness of breath—and, sometimes, death.

Action Taken

Rapid response from FDA and USP was essential to revising heparin-related standards to protect patients and rebuild confidence in the heparin supply. The two organizations have collaborated with industry and other partners over a comprehensive three-stage process. Click on the link below to view a timeline of this process.

The Value of Collaboration

At the time, Roger L. Williams, M.D., USP's chief executive officer, noted that the expedited revision of USP's heparin standards gives manufacturers, healthcare practitioners, and patients increased confidence that this widely used drug is free of contaminants. According to Williams, “The monograph revisions were...accomplished through USP's established, transparent and scientific process....USP received guidance and direction not only from the FDA but also from the volunteer experts on USP's Heparin Advisory Panel, Blood and Blood Products Expert Committee...Reference Standards Committee...and many other national and international experts..." Read More

This was corroborated by Ali Al–Hakim, Ph.D., FDA's branch chief and heparin expert at the Office of New Drug Quality Assessment during a subsequent USP heparin workshop, where he commended the “Update of [the] heparin monograph based on the constructive and successful collaboration between USP, FDA, and other parties...”

FDA Commissioner Margaret Hamburg, M.D., underscored the danger and the value of the response to the heparin crisis in her address to the USP Convention meeting in April of 2010, citing the incident as an example of strong public-private partnership success in protecting public health.

What We Learned

One of the lessons driven home by this highly visible and tragic incident is that global drug supply chains are vulnerable and must be vigilantly safeguarded at every stage. That includes the need to upgrade existing public quality standards for pharmaceuticals, and to develop new ones as well. Work to further strengthen and modernize tests for heparin and other legacy drugs is an ongoing collaboration among FDA, USP, pharmaceutical manufacturers, and regulatory bodies in other countries.

View the Latest Information on USP's Work Regarding Heparin