Synthetic Heparin on the Distant Horizon

How and when the potentially fatal contaminant oversulfated chondroitin sulfate wound up in lots of Baxter's Chinese-made heparin remain unknown. The synthetic contaminant, probably introduced at the workshop level, is believed to have caused more the 80 deaths and hundreds of adverse reactions in Americans during the last year. However, the longstanding process of producing heparin from pig intestines—a process susceptible to the introduction of infectious and foreign substances—may be threatened in the long term.

The laboratory production of heparin was reported Monday by Robert Linhardt, PhD, from the Rensselaer Polytechnic Institute at the ongoing meeting of the American Chemical Society in Philadelphia. At a press briefing, Linhardt described investigators' small-scale production of synthetic heparin by using the bacterial strain Escherichia coli K5. The bacteria naturally produces the polysaccharide backbone of heparin, heparosan,* which can be modified by recombinant mammalian enzymes and cofactor recycling to create a substance that is identical to the USP form of heparin.

The chemical production of heparin from E. coli, however, is presently limited to mg quantities (the current world market consumption of heparin is 100 metric tons per year), and Linhardt advises that the next step is to ramp up synthetic heparin production to the kg level during the next 5 years to enable preclinical and clinical study. He anticipates that the biggest hurdles to the large-scale production of heparin will relate to the downstream modifications of the polysaccharide backbone. Peer-reviewed details of the production process will be presented in an upcoming issue of the Journal of the American Chemical Society.

Linhardt admitted to interest from pharma and biotech companies in the production of synthetic heparin but warned that commercial entities are awaiting further development—ostensibly because heparin produced by current methods is so cheap.

* The only other organism, outside of animals, that is known to produce heparosan is the pathogen Pasteurella multocida.

Image of heparin chemical structure from Wikipedia.

HT: MedPage Today