Sophisticated Analytic Techniques Detect Unknown Material in Recalled Heparin

The heparin impurity in the active pharmaceutical ingredient (API) lots associated with adverse clinical events was found to be very similar chemically to the heparin molecule itself. Heparin is composed of many sugar-like units, and likewise, the impurity contains polysaccharides. One reason it has been difficult to determine the precise chemical structure of the impurity is because it is so similar to heparin, making it hard to separate the two in sophisticated chemical analyses.

Through its investigations to date, Baxter has ruled out protein impurities in the suspect heparin API. Therefore, bacterial-derived protein molecules such as pertussis, botulinum, shiga, diphtheria, cholera, and tetanus toxin, have been ruled out as the heparin impurity. Other chemicals such as tetrodotoxin (from puffer fish), lead, and dioxins (formed when hydrocarbons with chlorine are burned) also do not match the identified heparin impurity.

Although Baxter's analysis is not complete, the company has evidence that the unknown material is a highly sulfated glucosaminoglycan-like (GAG-like) material. While heparin-like, the material is structurally different from naturally occurring heparin. The unknown material has approximately the same molecular weight as heparin and is similar in other ways, which is why standard testing would not detect its presence.

The heparin is supplied to Baxter by Scientific Protein Laboratories (SPL; Waunakee, WI, USA).

"In this investigation, there are three key questions that we are trying to answer--what exactly is the contaminant, where in the supply chain was it introduced, and can we prove that this contaminant is in fact causing the reactions we've seen,” explained Norbert G. Riedel, corporate vice president and CSO of Baxter International, Inc.

The continued collaboration between Baxter, FDA [U.S. Food and Drug Administration (Rockville, MD, USA)], and SPL, as well as the consolidators, workshops, and other links in the supply chain, is critical to putting all of the pieces together and determining root cause. Baxter remains committed to facilitating this collaboration and providing the technical expertise necessary to resolve this issue. We stand ready to assist SPL and regulatory authorities in implementing additional measures to ensure that this does not happen again,” Mr. Riedel concluded.


Related Links:
Baxter
Scientific Protein Laboratories
U.S. Food and Drug Administration