Discovery announced in Science Represents 'New Paradigm' İn The Way Drugs Can Be Manufactured

Robert Linhardt is working to forever change the way some of the most widely used drugs in the world are manufactured. In a new studying appearing in the journal Science, he and his partner in the research, Jian Liu, have announced an important step toward making this a reality. Linhardt, the Ann and John H. Broadbent Jr. '59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer Polytechnic Institute, and Jian Liu, a professor in the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill, have discovered an entirely new process to manufacture ultra-low molecular weight heparin.

The research shows that the drug is identical in performance and safety to the current and successful anticoagulant fondaparinux, but is purer, faster, and less expensive to produce.

"This research represents an entirely new paradigm in drug manufacturing," Linhardt said. "With this discovery, we have successfully demonstrated that replacing the current model of drug production with a chemoenzymatic approach can greatly reduce the cost of drug development and manufacturing, while also increasing drug performance and safety, and reduce the possibility of outside drug contamination. It is our hope that this is the first step in the adoption of this method for the manufacture of many other drugs."

The new process uses chemicals and enzymes to reduce the number of steps in production of fondaparinux from approximately 50 steps down to just 10 to 12. In addition, it increases the yield from that process 500-fold compared to the current fondaparinux process, and could decrease the cost of manufacture by a similar amount, according to Linhardt.

Fondaparinux, which is sold as a name-brand drug and was also recently approved by the FDA as a generic drug, is a synthetic anticoagulant used to treat deep vein thrombosis, with over $500 million in annual sales. It is part of a much larger family of anticoagulant drugs known as heparins. But, unlike most heparin products, it is chemically synthesized from non-animal materials. All other heparin-based drugs currently on the market use materials from the intestines of pigs and lungs of cattle as source materials. Such animal materials are more likely to become contaminated, according to Linhardt.