The pursuit of a synthetic version of heparin, free of animal materials and made with stricter quality controls, is gaining more attention as awareness grows that the blood thinner can be sourced from an unregulated supply chain that starts with hog lots in rural China.
The U.S. Food and Drug Administration this week disclosed that low-cost animal cartilage made its way into Baxter International Inc.’s heparin, raising fears conventional quality-control procedures do not adequately protect American consumers. Baxter’s product, recalled in the U.S. last month, has been linked to hundreds of potentially dangerous allergic reactions and at least four deaths. On Friday, the FDA said another American heparin-maker, B. Braun Medical Inc., recalled, as a precaution, more than 20 lots made by the same Chinese plant that supplied Baxter.
“The reason we are pushing for the synthetic is that you can completely control the production process,” said Jian Liu, associate professor of medicinal chemistry and natural products at the University of North Carolina School of Pharmacy, who is developing a synthetic heparin that is years from the U.S. market. “For the time being, we are stuck with the pig stuff. It has served us well for 50 years, but it was only a matter of time until something like this happened. It is too easy for the heparin extraction process to be contaminated if strict controls are not maintained.”
The synthetic process purifies the drug and its ingredients every step of the way in laboratories, in contrast to the need for scrutiny of village workshops and farms in China that are now under investigation by U.S. and Chinese health officials.
The FDA on Wednesday said as much as 50 percent of Baxter’s heparin tested from suspect lots recalled showed that the raw ingredient used to make the drug contained oversulfated chondroitin sulfate, an unapproved dietary supplement taken orally to treat joint pain.
Synthetic heparin has its own drawbacks, however. It is complex to make and development costs could push the price up between five and 40 times the $1 per-vial cost of the decades-old heparin, researchers and analysts said.
“It’s been inexpensive to derive heparin from animal sources so that there has been little incentive to consider a synthetic version of this particular heparin,” said FDA spokeswoman Karen Riley.
Indeed, Wisconsin-based Scientific Protein Laboratories four years ago opened a manufacturing plant in Changzhou, China, to keep its heparin costs low. Scientific Protein, which supplied active ingredients used to make heparin for both Baxter and B. Braun, made the move to China after supplies of pigs were inadequate in the U.S. and Canada.
Currently, there is no FDA-approved synthetically derived heparin with the broad indications awarded Baxter’s heparin, which is used for dialysis and before heart surgery. The synthetics that are available are approved for specific uses, the FDA and researchers said.
The push for synthetic heparin also comes as some industry experts wonder whether there could one day be supply issues with pigs just like there were concerns decades ago from international health officials about shortages of cow and pig pancreases that had been used for decades to make insulin.
Such concerns in the 1980s forced insulin-makers like Eli Lilly & Co. to begin to move to synthetic versions as the world’s diabetes epidemic began to take off. In 2005, the Indianapolis-based drug giant produced its last insulin derived from pigs. “If we did not think of better ways to produce it, we could be facing a potential problem because the diabetes epidemic was starting,” Lilly spokesman Scott MacGregor said.
Synthetics are being pursued in other areas. This spring, biotech company Discovery Laboratories Inc. of Warrington, Pa., expects to win FDA approval to market a synthetic lung treatment, Surfaxin, for respiratory diseases in premature babies. It hopes to compete with North Chicago-based Abbott Laboratories’ cow-derived product known as Survanta.
Proponents of synthetics claim they’re safer. “Animal-derived products carry the risk of developing an immune response,” said Thomas Miller, senior vice president of commercial operations for Discovery.
Analysts said Surfaxin, once it’s approved by the FDA, could be $200 to $400 a vial more expensive than Abbott’s product, and Discovery will have to convince insurance companies the expense is worth it. But Miller believes doctors and hospitals will find it as a long-overdue alternative.
“If it was my child, this would be my choice,” Miller said. “I don’t think cost would be at the top of my mind in my decision analysis.”
Abbott, however, said “there is no evidence that synthetic sources are inherently safer or more efficacious than naturally derived ones.”
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bjapsen@tribune.com
