Concerns about safety of blood thinner heparin

[Al-khiyal]

Blood thinner concerns spread to Germany

WASHINGTON, March 7, 2008: Concerns about the safety of the blood thinner heparin have spread to Germany after drug authorities there received reports of patients being sickened after getting the drug.

Meanwhile, U.S. Food and Drug Administration officials also announced Thursday that they were asking all companies in the United States that produce heparin to test it with two new procedures.

The complex tests, nuclear magnetic resonance spectroscopy and capillary electrophoresis, are the only ones that can uncover whether the drug contains a possibly counterfeit ingredient.

Dr. Janet Woodcock, deputy FDA commissioner, said that the agency would post instructions online for how to conduct the tests.

FDA officials said Wednesday that a possibly counterfeit ingredient had been found in certain batches of heparin linked to at least 19 deaths in the United States and more than 700 severe allergic reactions.

Federal officials said they could not yet say that the contaminant, which mimics real heparin, caused the reactions.

Until Thursday, federal investigators had been focusing on heparin manufactured by Baxter International. But Woodcock said that German health authorities told the FDA that Baxter did not make the heparin linked to two separate outbreaks of allergic reactions in that country. Germany has reported fewer than 100 cases of patients suffering severe allergic reactions and shock, and no deaths.

FDA officials declined to say whether the raw ingredients for the suspect German heparin came from China, the source of the starting materials used to make the contaminated heparin in the United States.

Most of the world's heparin supply is from China. In the last six months, more than 30 Chinese companies could be found selling heparin products on major business-to-business Web sites.

"We are working as quickly as possible to analyze any potential impact on the U.S. market and worldwide," said Deborah Autor, the director of compliance for the agency's Center for Drug Evaluation and Research.

In the first half of last year, China exported heparin product to 42 countries and regions, according to a September 2007 report by the China Chamber of Commerce for Import and Export of Medicines and Health Products. China exported the most heparin products, about 13 tons, to Germany. It also sent 11 tons to France and about 10 tons to the United States, the report said.

Erin Gardiner, a spokeswoman for Baxter, said reports that her company was not responsible for making the suspect heparin in Germany most likely point to a problem with the suppliers of crude heparin. "The news today indicates that the issue could be further back in the supply chain," Gardiner said.

Last week, Baxter withdrew from the market nearly all of its heparin products.

Baxter bought the active pharmaceutical ingredient for its heparin products from Scientific Protein Laboratories, based in Waunakee, Wisconsin, which has plants in Wisconsin and Changzhou, China. All of the suspect heparin was made from raw heparin produced in China. In some cases, those supplies were produced in small, unregulated family workshops, according to heparin traders and producers in China.

Scientific Protein Laboratories announced Wednesday a recall of some of its product, the active ingredient in heparin.

Most supplies of heparin in the United States are now from APP Pharmaceuticals, of Schaumburg, Illinois. APP's supplies have undergone the new tests.

German authorities have identified Rotexmedica as a manufacturer of at least some of the suspect heparin there, FDA officials said.

German drug authorities could not be reached. FDA officials said they were told that the German authorities had recalled an unspecific amount of heparin.

In a statement released Thursday, Scientific Protein Laboratories said, "We believe this demonstrates that the heparin problem is not within Changzhou SPL's or Baxter's manufacturing facilities but our investigation into the root cause of the problem will continue."

Representative John Dingell, a Democrat of Michigan who chairs the House Energy and Commerce Committee, charged in a statement released Thursday that the FDA "is drowning in drug imports that it is not able to properly regulate."

In Europe, such foreign inspections may be even rarer. A 2006 report by a European chemical association said that even when European inspectors find serious safety issues, European regulators do not suspend the producers from supplying the European market because of a lack of government coordination.

[Bent_Bladi]

The complex tests, nuclear magnetic resonance spectroscopy ...

ah... so that's where NMR is useful

ya latif though, alhamdulilah for modern technology

[amalgamate]

oh oh- some counterfeit drug? Heparin? yalateef

[Al-khiyal]

U.S. health officials identify contaminant in blood thinner

March 20, 2008 -- U.S. drug regulators, in announcing Wednesday that the mystery contaminant in heparin was an inexpensive, unapproved ingredient altered to mimic the real thing, moved closer to concluding that Americans might be the latest victims of lethal Chinese drug counterfeiting.

The finding by the Food and Drug Administration culminated a worldwide race to identify the substance discovered early this month in certain batches of heparin, the blood-thinning drug that had been linked to 19 deaths in the United States and hundreds of allergic reactions.

The contaminant, the regulators said, is a chemically altered form of chondroitin sulfate, a dietary supplement made from animal cartilage that is widely used to treat joint pain. The agency's announcement followed a report Wednesday in The New York Times that was the first publicly to identify the modified substance as the likely contaminant. That report was based on nearly two dozen interviews with researchers and scientists in China, the United States and Canada.

U.S. officials stopped short of saying that the contaminant — constituting as much as 50 percent of the active ingredient in heparin — was counterfeit. "At the moment we don't know definitely whether the contaminant was introduced intentionally or by accident," said Dr. Janet Woodcock, director of the Food and Drug Administration's center for drug evaluation and research.

Even so, the authorities left little doubt that they believed that the contaminant was not an unintended byproduct of some manufacturing process.

In its natural state, chondroitin sulfate does not have anticlotting properties. But it mimics heparin when altered to form what is called oversulfated chondroitin sulfate. That is what made it difficult for Baxter International, the manufacturer of the heparin associated with the allergic reactions, to detect the impurity. "This compound to our knowledge is not naturally occurring," Dr. Woodcock said. "It should not be in heparin. And it obviously should not be in the form it is in."

While identifying the contaminant was a significant breakthrough, investigators still do not know if it is responsible for causing the allergic reactions. Nor do they know why the modified ingredient ended up in heparin, though they have raised the possibility that the substance was used as cheap filler.

"The base compound, chondroitin sulfate, is very abundant and an inexpensive compound," said Moheb Nasr, director of the agency's office of new drug quality and assessment. Chemically modifying it, Nasr added, "will not be that expensive either."

The FDA said it had found the contaminated heparin at Changzhou SPL, the Chinese plant that supplies the active ingredient to Baxter. Changzhou in turn buys its heparin from two companies, called consolidators, that gather crude heparin from workshops that make it from pig intestines.

Many workshops that make crude heparin are unregulated family operations.

Erin Gardiner, a spokeswoman for Baxter, said Wednesday that tests found the supplies were contaminated before they arrived at the Changzhou plant. "The consolidators and workshops handle the crude material, so that is where our focus is turning," Gardiner said.

So far, Gardiner said Baxter's investigators had been denied access to the consolidators and workshops. "We will continue to seek access."

Last week, the FDA said it had not yet visited the workshops.

Some heparin producers in China also sell chondroitin sulfate, which can be derived from pig cartilage. Traders and producers say it is far cheaper than heparin, as little as one-twentieth the cost. That could be an enticement for counterfeiters, especially in the wake of a virulent pig virus that swept across China last year, substantially reducing the availability of the starting materials needed to make the active ingredient in heparin.

Contaminated heparin sourced from China has also turned up recently in Germany, where about 80 allergic reactions have been reported. But investigators there have yet to identify the contaminant. FDA officials said their discovery of chemically modified chondroitin sulfate came exactly one year after the discovery that a pet food ingredient shipped from China contained toxic levels of melamine, which was added to make it appear higher in protein. Many pets became ill, and some died.

Around the same time, The Times reported that an unlicensed Chinese chemical plant sold a cheap counterfeit ingredient, diethylene glycol, that was mixed into cold medicine in Panama, killing nearly 120 people and disabling dozens more.

Diethylene glycol mimics its more expensive chemical cousin, glycerine, a safe ingredient used in medicine, food and toothpaste.

The FDA said its search for answers in the heparin case had been made easier because of the cooperation it had received from China's State Food and Drug Administration. That was not the case when United States officials inquired last year about the melamine and diethylene glycol.

The agency cited an accord signed in December by the governments of China and the United States as one reason for the cooperation they had received recently, which they said allowed American investigators to quickly begin their investigation of the additive.

Baxter has recalled virtually all of its heparin products. The FDA has also asked that all heparin entering the country be stopped and tested for the contaminant. Heparin is commonly used in dialysis and cardiac surgery. "We feel doctors and patients can be confident that the product on the market for the large volume uses of heparin, for dialysis and so forth, has been tested and is safe," Dr. Woodcock said.

[amalgamate]

Americans might be the latest victims of lethal Chinese drug counterfeiting.

oh yea sure, point the finger at China for this.

[amalgamate]

FDA officials declined to say whether the raw ingredients for the suspect German heparin came from China, the source of the starting materials used to make the contaminated heparin in the United States.

I'm scepticle that the problem originated from china. I wonder about the purity of ingredients the manufacturers use in the US.

[Al-khiyal]

Heparin contamination may have been deliberate, F.D.A. says

WASHINGTON, April 30, 2008 — Federal drug regulators believe that a contaminant detected in a crucial blood thinner that has caused 81 deaths was added deliberately, something the Food and Drug Administration has only hinted at previously.

“F.D.A.’s working hypothesis is that this was intentional contamination, but this is not yet proven,” Dr. Janet Woodcock, director of the Food and Drug Administration’s drug center, told the House Subcommittee on Oversight and Investigations in written testimony given Tuesday.

A third of the material in some batches of the thinner heparin were contaminants, “and it does strain one’s credulity to suggest that might have been done accidentally,” Dr. Woodcock said.

Two weeks ago, Food and Drug Commissioner Andrew C. von Eschenbach told a Senate subcommittee that the contamination was done “by virtue of economic fraud,” but he quickly withdrew the remark, saying he had “probably gone too far.”

Dr. Woodcock’s statement on Tuesday was part of growing chorus that has labeled the heparin contamination as perhaps the most brazen poisoning episode since 1982, when seven people in the Chicago area died after taking Tylenol that had been laced with cyanide.

The Tylenol case led to substantial changes in product packaging, and the heparin contamination has led both Democratic and Republican committee members to call for major changes in the way the F.D.A. functions and is financed.

Tuesday’s hearing was also the first in which family members of those who died were asked to testify.

LeRoy Hubley of Toledo, Ohio, described how both his 65-year-old wife and his 47-year-old son died within a few weeks of each other. Both suffered from a genetic kidney disease that required constant dialysis, for which heparin is routinely used.

“As Christmas music softly played in the background, we each said our goodbyes,” Mr. Hubley said, breaking down in tears. “Then my wife and love of 48 years drifted away.”

He did not know for weeks after their deaths that his wife, Bonnie, and son, Randy, had been given contaminated heparin.

“Now I am left to deal not only with the pain of losing my wife and son, but anger that an unsafe drug was permitted to be sold in this country,” he said.

David G. Strunce, chief executive of Scientific Protein Laboratories, the company that supplied contaminated heparin material to Baxter International, which manufactured and distributed the finished drug, described the contamination as “an insidious act” that “seems to us an intentional act upstream in the supply chain.”

The F.D.A. has identified Changzhou SPL, a Chinese subsidiary of Scientific Protein Laboratories, as the source of the contaminated heparin. A Congressional investigator said the contaminant, oversulfated chondroitin sulfate, cost $9 a pound compared with $900 a pound for heparin.

Mr. Strunce said that his company tried to find the original source of the contamination but was stopped by the Chinese authorities.

Robert L. Parkinson, Baxter’s chairman and chief executive, told the committee, “We’re alarmed that one of our products was used in what appears to have been a deliberate scheme to adulterate a life-saving medication.”

Chinese officials have disputed the F.D.A. contention that the contaminant caused death and injury, and they have insisted on the right to inspect American drug plants if the F.D.A. insists on inspecting Chinese ones.

David Nelson, a Congressional investigator, told the House panel that had the F.D.A. inspected the Chinese plant, the contamination could have been averted.

F.D.A. officials have admitted that they mistakenly failed to conduct an inspection of the Changzhou SPL plant but said that an inspection would not have been able to uncover the contamination.

The agency finally conducted an inspection of the facility in February and found so many problems that the F.D.A. blocked the plant from exporting to the United States. Mr. Nelson was even more critical of Baxter International, which bought heparin ingredients from Changzhou SPL from 2004 through 2008 but did not inspect the facility until September 2007.

The company sent one person who spent one day in the plant, Mr. Nelson said. Five months later, the F.D.A. discovered myriad problems, he said.

“It really is impossible for a plant to have fallen that far out of compliance in five months,” Mr. Nelson said.

Under withering questioning, Dr. Woodcock said that the F.D.A. would need another $225 million annually to inspect every foreign drug plant every other year, the frequency most say is needed. The agency will spend $11 million this year on foreign drug inspections.

There is a growing bipartisan consensus on Capitol Hill that the F.D.A. needs a rapid increase in its budget to ensure the safety of the nation’s drugs, medical devices and food.

The Bush Administration has proposed increasing the agency’s budget next year by only 3 percent to $1.8 billion, not enough to cover even its expected cost increases.