Full article reprinted from PharmAsia News - August 7, 2009
BEIJING - When heparin sourced from China mysteriously and suddenly began triggering a spike in extreme adverse reactions and deaths across American hospitals 18 months ago, U.S. FDA rapidly called on the U.S. Pharmacopeial Convention to help devise new testing methods to determine the purity and quality of the blood thinner. Read on...
Full article reprinted from PharmAsia News - August 7, 2009
As the casualties shot upwards, USP and FDA scientists worked at a frenetic pace to figure out why heparin had virtually overnight become so dangerous.
Now, the U.S. Pharmocopeia is releasing a second phase of revisions in its written and physical standards for the widely used blood thinner; the new standards include special testing technology that can be used to detect oversulfated chondroitin sulfate, a chemical whose molecular structure so closely resembles heparin that it could not be differentiated in previous tests.
FDA investigations have uncovered evidence that oversulfated chondroitin sulfate, which is much cheaper to produce than heparin, had been used to spike shipments of the blood thinner exported to the U.S. and other countries by an array of Chinese companies.
U.S. FDA Request For New Heparin Standards
"In February, USP released updated heparin standards at the request of the Food and Drug Administration in response to the 2008 public health crisis in which more than 200 people died as a result of heparin adulterated for economic gain," said Francine Pierson, a spokesperson at USP. "A second phase of revisions is reflected in the newly posted standards."
FDA has already issued formal warning letters to three China-based suppliers of heparin that were implicated in the contamination, and might attempt to impose criminal penalties sometime in the future (The Pink Sheet Daily, April 23, 2009).
Meanwhile, "the new [USP] standards will become official on October 1, and they will definitely significantly increase the protection of public health against adulteration of heparin, and thus are expected to further decrease the likelihood of adverse events," said Tina Morris, USP vice president of biologics and biotechnology.
The U.S. Pharmacopeial Convention has also been working to step up cooperation with Chinese scientists and regulators, with a series of agreements signed since last year with the Chinese Pharmacopoeia Commission, with China's National Institute for the Control of Pharmaceutical and Biological Products, which supervises quality controls for drugs across the country, and with Chinese provincial-level authorities (PharmAsia News, June 26, 2009).
USP Standards As Global Benchmark
USP, established nearly two centuries ago, is a scientific organization that sets standards for the quality of prescription and over-the-counter drugs that are enforced by in the U.S. by FDA. Although initially created to help ensure drug quality in the U.S., USP standards have since become benchmarks for more than 100 states across the planet, and the group's 700-member Council of Experts has begun to resemble the United Nations, with scientists elected to the Council from around the world.
Chinese scientists have already joined the USP Council of Experts, and one is a member of the Reference Standards Expert Committee that approved the new heparin reference materials.
Pierson said that the new standards for the blood thinner were the focus of a recent workshop hosted by the USP at its headquarters in Rockville, Maryland.
"The workshop, co-sponsored by USP, the British National Institute of Biological Standards and Control, and the European Directorate for the Quality of Medicines, reflected the global nature of both the problem of adulteration and the resources cooperating to combat it, with attendees from more than 17 countries," she explained.
VP Morris said that workshop "attendees came from Italy, Spain, Germany, France, the U.K., the U.S., China, Korea, Japan, Argentina, Brazil, and India, to name but a few."
When queried whether USP's expanding range of contacts and cooperation with Chinese scientists and public health authorities could eventually include joint endeavors in the area of testing for contaminated heparin, Morris said that remains a possibility.
"The USP already has memoranda of understanding with the Chinese Pharmacopeia and the National Institute for the Control of Pharmaceutical and Biological Products," she explained. "While the projects covered by those agreements currently do not include heparin-related work, there is always future opportunity."
The surge in cases of heparin contaminated in China for economic gain, early in 2008, was followed by a similar scandal marked by milk spiked with the toxic chemical melamine in order to fool protein tests and sold across the country until detected one year ago.
U.S. FDA Issues Melamine Guidance
After monitoring melamine contamination cases for the past year, the U.S. FDA this week issued a "guidance" report that stated: "Certain pharmaceutical ingredients used in the manufacture or preparation of drug products should be tested for melamine."
"Melamine," FDA authorities explained, "is a synthetic chemical with a variety of industrial uses including the production of resins and foams, cleaning products, fertilizers and pesticides. If ingested in sufficient amounts, melamine can result in kidney failure and death."
The agency said that Chinese incidents of melamine-tainted milk had pointed to a "potential problem" that pharmaceuticals sold in the U.S. could be similarly adulterated.
"The FDA urges implementation of appropriate controls to assure consumers that melamine contamination will not happen in the pharmaceutical supply chain," said FDA Commissioner Margaret Hamburg in the guidance statement.
The FDA has identified specific pharmaceutical ingredients that should be screened for the presence of melamine, and is developing a testing program for drug ingredients at risk for melamine contamination.
- Kevin Holden
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