Heparin is routinely given to patients before certain types of surgery and prior to treatments such as kidney dialysis to prevent blood clots from forming. Clots that do not naturally dissolve can travel through the blood stream and end up in the brain, causing stroke or in the lungs resulting in a pulmonary embolism.

Heparin is produced naturally by most animals, including humans, but most heparin used today is derived from pig intestines. China has become a popular location for manufacturing heparin because it has a much larger pig population. It is somewhat inexpensive to produce, however, ensuring the safety of drugs manufactured overseas has been a challenge for the Food and Drug Administration (FDA). Just last year, more than 80 Americans died and hundreds more were sickened after they received injections of specific batches of heparin that were manufactured in China. That heparin was later found to have been contained with oversulfated chrondroitin sulfate (OSCS). As a result, researchers have been working to find safer alternatives to heparin.

Liu, whose Recomparin research was published online in the Proceedings of the National Academy of Sciences journal last November, says he is also looking into customizing heparin for other uses, such as a treatment for small-cell lung cancer.

SOURCE: Heparin Recall › Researcher awarded NIH grant for development of synthetic heparin

“Previously it was nearly impossible to change the nature of the heparin generated by the enzyme,” said Jian Liu, Ph.D., associate professor at the UNC Eshelman School of Pharmacy medicinal chemistry and natural products division. “The degree of difficulty was 10-plus. Now it’s more like a two or three, which opens the door to the possibility of improving on the natural product.”

The method involves modifying the enzyme heparan sulfate 2-O-sulfotransferase, which produces heparin in the human body in addition to other heparin-like molecules. By modifying 2-O-sulfotransferase, researchers will be able to create customized forms of synthetic heparin with different properties, according to the report.

Heparin is typically administered to most patients during surgery and before some treatments such as kidney dialysis to prevent blood clots from forming. Heparin is produced naturally by most animals, including humans, but most heparin available today is derived from pig intestines. China has become a popular location for manufacturing heparin because it has a much larger pig population.

However, heparin manufactured in China raised concerns earlier this year after batches from Baxter International’s China plant were found to have been contaminated. The investigation into heparin resulted after more than 80 Americans died and hundreds more were sickened after receiving doses of the tainted heparin. As a result, researchers have been working to find safer alternatives to heparin, including developing synthetic versions.

“The pig stuff has served us well for 50 years and is very inexpensive, but if we cannot control the supply chain, we cannot ensure the safety of the drug,” Liu said. “I am working for the day when synthetic heparin can be brewed in large laboratories at a low cost.”

Liu and her colleagues also are looking into customizing heparin for other uses, such as a treatment for small-cell lung cancer.

Liu’s research recently was published online in the journal Proceedings of the National Academy of Sciences.

SOURCE: Heparin Recall › Scientists on road to modifying, customizing human heparin

The active ingredient in heparin is derived from pig intestines and the demand for the drug has become so great that the domestic pig population cannot meet the demand. To meet the immediate need, pharmaceutical companies have turned to China, which has three times the pig population.

But importing drugs from China has raised some serious concerns. Earlier this year, 81 people died and hundreds more were sickened after receiving doses of heparin, which was later found to have been contaminated in a Chinese manufacturing plant.

As a result, scientists are eagerly working to develop a synthetic version of heparin that could be made in U.S. labs, thus preventing future scares. In August, we told you about Rensselaer Polytechnic Institute’s Robert Linhardt, who had just announced that after years of work his research team appeared to have successfully devised a synthetic heparin.

Linhardt and his team continue to forge ahead with the synthetic drug, according to the Scientific American. The challenge, however, is that it is hard to mass produce. It took a year for Linhardt and his team to produce 100 milligrams of the synthetic version, which pales in comparison to the more than 100 metric tons of heparin needed to meet the world’s demand for just one year.

Linhardt hopes to have a gram of synthetic heparin – or enough to give 100 doses to mice to start animal trials – within a year. Far more of the synthetic drug would be needed for clinical testing on patients, presenting a further challenge. Cost could become another issue, as heparin made from pig intestines costs only about 20 cents per dose and making the synthetic version a feasible business would take years and a huge investment.

However, Linhardt says mass production of the synthetic heparin would have benefits that far outweigh the negatives: “The future is one that will be short continuously of heparin,” he was quoted in Scientific American. “Which means any adulterations of the heparin (imported by the U.S.), we’re going to have to live with—or catch.”

SOURCE: Heparin Recall › Scientists work to overcome obstacles in synthetic heparin

Alchemia’s CEO, Dr Peter Smith said “The impending commercialization of generic fondaparinux and anticipated revenues in calendar year 2009 will form a strong financial base for Alchemia. This will enable the company to advance its drug targeting and drug discovery technologies to further build a sustainable pipeline of opportunities for future commercialization.”

The company’s report states: “Given the complexity of the synthesis, Alchemia continues to believe that its generic fondaparinux will be the only generic brought to market, restricting competition to two drugs, Alchemia’s fondaparinux and GSK’s Arixtra. Typically, a first generic will take 40-50 percent of the prescription share, and with Alchemia’s fondaparinux expected to be the sole generic, a modest level of price discounting is anticipated.”

Arixtra is the only heparin drug not derived from biological sources as it is a synthetic molecule. Thus, it was not among the recent heparin recall.

Alchemia contends that there are no significant technical hurdles remaining and that generic fondaparinux approval and launch is expected in the first half of 2009, depending on review time at the FDA.

SOURCE: Heparin Recall › Synthetic heparin expected to launch early 2009

The NanoBioTech 2008 conference was held Monday at the Institute, and addressed topics including the developments in nanotechnology law, protecting intellectual property, and attracting investors, according to an article in the Times Union.

Linhardt presented information about research that combines heparin, an anticoagulant, with cellulose to create a membrane that can be used in kidney dialysis, the report says. The work also moves scientists closer to creating a “paper battery,” which is that same membrane strengthened with carbon nanotubes that act as electrodes.

According to the Times Union story, Linhardt told the conference audience that the battery can be powered by the body’s own fluids, like blood, sweat or tears, which act as electrolytes. The battery is an energy storage device that can be implanted in the body to provide power to operate medical devices like pacemakers, defibrillators and pumps, the scientist says.

SOURCE: Heparin Recall › Heparin utilized in nanotechnology

Linhardt was among the researchers who discovered the source of tainted heparin that was responsible for at least 149 deaths since the beginning of 2007. Manufacturer Baxter International, which supplies about half of the heparin used in the U.S., recalled its supplies of heparin made in China after more than 80 patients suffered serious allergic reactions and death following its use.

According to a report by Bloomberg News Service, Chinese pig farms that provide source material for heparin are not monitored by the U.S. Food & Drug Administration, which increases the risk for contamination. Continued use of traditional heparin products manufactured in these facilities leaves the door open for another contamination event, Linhardt says in the Bloomberg report.

In addition to Baxter’s product, a smaller scale contamination problem was reported with the Lovenox heparin medicine manufactured by Sanofi-Aventis, according to a report by Reuters.

Linhardt presented his team’s synthetic heparin results at the recent American Chemical Society meeting, according to Reuters, where he told those in attendance that today’s heparin manufacturing methods are “simply unsafe.”

Scientists are working on creating larger quantities of the synthetic heparin, which Linhardt hopes will reach human clinical trials in five years, Reuters reports.

SOURCE: Heparin Recall › synthetic heparin in development