Baxter Heparin Recall: A Sad Chronology Of Events

On March 19, 2008, the FDA identified the contaminant found in Baxter heparin as oversulfated chondroitin sulfate. Chondroitin sulfate is a natural occurring chemical compound derived from animals and is commonly found in dietary supplements. However, the oversulfated variation of chondroitin sulfate does not occur naturally, but is rather a chemically modified compound. The FDA has not yet discovered how the contaminant found its way into the heparin, but has traced the compound back to a manufacturing plant in China owned and operated by Scientific Protein Laboratories (SPL), a company that supplies crude heparin to Baxter. Oversulfated chondroitin sulfate was able to pass for heparin in a number of pre-market tests. The FDA noted that chondroitin sulfate is an abundant and cheap chemical compound, and modifying it is also very inexpensive.

On March 5th, 2008, FDA officials announced the discovery of a "heparin-like molecule" in the crude heparin manufactured by Scientific Protein Laboratories (SPL), and supplied to Baxter International to make its heparin. This molecule appears similar to heparin, but is considered a contaminant of the heparin. Because of the molecule's similarity to heparin, routine tests did not detect its presence. The details as to how the molecule found its way into SPL's product are currently unknown. FDA scientists estimate that the molecule could be found in up to 20% of the sample product tested. According to the FDA, there is likely an association between the molecule and the severe reactions recently experienced by those taking Baxter heparin. However, the FDA has not yet established a direct causal link. The FDA is continuing to study Baxter heparin and the contamination with this heparin-similar molecule.

On January 17, 2008, Baxter Healthcare Corporation initiated a recall of nine lots of heparin sodium injection multi-dose vials. These vials were distributed in two sizes: 1000 units/mL 10 mL vials and 1000 units/mL 30 mL vials. Baxter recalled these lots because of a spike in adverse events reports associated with the use of Baxter heparin sodium injections. The recall came after Baxter received more than 350 reports of adverse events in January of 2008. Baxter received only 100 reports in all of 2007. The initial recall noted a number of problems that were associated with the use of Baxter heparin, including: abdominal pain, decreased blood pressure, chest pain, diarrhea, nausea, vomiting, increased heart rate, fainting, shortness of breath, unresponsiveness, redness of skin, flushing, increased sweating, thirst, abnormal skin sensations, watery eyes, and throat swelling, inability to open mouth, and headache. The recall warned that reactions to heparin could be severe and life threatening.

-Link to 1/25 FDA Notice of Recall http://www.fda.gov/Safety/Recalls/default.htm

On February 11, 2008, Baxter released an update on its recall of the heparin sodium injection. In addition to the nine recalled lots, Baxter received reports of similar adverse events from other lots of heparin sodium injection vials, including vials of different sizes and concentrations. The update released further that the heparin sodium vials are used almost exclusively during dialysis, invasive cardiovascular procedures, and apheresis. As well, the update of February 11th noted Baxter's decision, made in agreement with the FDA, to suspend production of further heparin, but not to recall any further lots due to market supply concerns. Therefore, Baxter's existing supply of heparin sodium injection vials was still distributed. The update advised healthcare professionals to balance the need for heparin with the increased possibility of reaction. As well, the

In addition to announcing further lots of vials associated with a spike in adverse event reports, the update also highlighted further possible reactions to the Baxter heparin. Notably, the update referenced profound and refractory hypotension as a severe and life-threatening condition. Refractory hypotension is spontaneous low blood pressure, despite adequate blood plasma, blood volume, and otherwise normal signs. Thus, the low blood pressure is induced by an obscure source, such as heparin. Refractory hypotension can result in a number of complications, including: organ damage, organ failure, shock, and death. Many patients may not know if they experienced refractory hypotension as a result of taking heparin.

On February 14th and 15th, the Wall Street Journal reported that the active ingredient in Baxter's heparin was supplied by a company known as Scientific Protein Laboratories (SPL). The active ingredient was manufactured at a facility in China. This facility was not inspected by the FDA prior to the reported increases in adverse events. The articles did not explicitly link the adverse events to problems with the facility in China. However, the FDA is in the process of inspecting the China facility, and its results have not yet been released.

-Link to Wall Street Journal articles Wall Street Journal Heparin Article

On February 28, 2008, Baxter announced its recall of all lots of all sizes of its multi-dose vials of Heparin Sodium injection, as well as single dose vials, and its heparin lock flush products. Baxter says this recall was made after the FDA confirmed adequate market supply of Heparin. The only Baxter heparin products that remained on the market after this recall were IV bags of heparin.

Link to 2/28 FDA Notice of Recall http://www.fda.gov/