Earlier this year, Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in 12 countries. In the US, other Heparin suppliers have issued precautionary recalls, and some medical devices makers have also recalled Heparin-coated products.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
Earlier this month, the FDA said that medical devices made with Heparin had been implicated in 11 additional deaths, and 86 more adverse reactions. Most of the cases involved Heparin used to clean intravenous lines. The Heparin associated with two of the 11 deaths wasn’t contaminated and the FDA is unable to conclusively say how many of the deaths and side effects involved the tainted Heparin. The FDA also did not identify which companies’ products were associated with the adverse reactions and deaths.
According to the FDA, it has now received reports of 248 deaths among people who had taken Heparin since Jan. 1, 2007. Of those, 149 were people who suffered allergic reactions. In most deaths, the FDA said it didn't have enough evidence to determine if Heparin was to blame. The number of reported deaths spiked in January at 50 and declined to five last month. The FDA said yesterday that all supplies of Heparin currently sold in the United States are safe.
The FDA has been under scrutiny lately, especially for its oversight of imported food and drugs. Since late last year, tainted Heparin sourced from China has been blamed for at least 81 deaths and hundreds of adverse reactions in the U.S. It was eventually learned that the FDA had never inspected the Chinese plant where raw Heparin ingredients were made.
Critic have long argued that the FDA does not have the funding or manpower to police the massive amounts of food and drugs imported from overseas. In May, the Heparin debacle prompted FDA Commissioner Andrew von Eschenbach wrote a letter to Sen. Specter recommending an additional $275 million for funding food and drug safety. That letter was not a formal request, but some observers were surprised that von Eschenbach had departed from the Bush Administration's official stance that no additional funding was needed.
The Administration finally changed it's tune this week, after an outbreak of Salmonella from tomatoes sickened 167 people in 17 states, and contributed to the death of a cancer patient in Texas. In a handwritten note on his letter, Sen. Specter said the "Administration is drastically hindering necessary immediate relief by delaying the funding for eight or nine months." A spokeswoman for Sen. Specter told The Wall Street Journal that he is referring to the Bush administration in the hand-written portion of the letter.
According to The Wall Street Journal, Sen. Specter had already been working to get the agency $275 million in the fiscal 2008 supplemental appropriations bill. The appropriations bill would require that the FDA receive the funding by September 30. But lawmakers are considering striking the FDA funding from the appropriations bill because of the recent Bush Administration request. Unfortunately, that would keep the FDA from getting additional funding for months.
"The 81 deaths due to contaminated Heparin and the one suspected death in the ongoing Salmonella outbreak show that we cannot wait nine months to give FDA the resources needed to protect the public," Sen. Specter said in the letter.
Earlier this year, Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. Ultimately, tainted Heparin injections have been blamed for more than 80 deaths and more than 700 adverse reactions in the U.S.
There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in a 12 countries. In the US, other Heparin suppliers have issued precautionary recalls, and some medical devices makers have also recalled Heparin-coated products.
In March, the Food & Drug Administration (FDA) confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It cost-*s a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
Last week, the FDA said that medical devices made with Heparin had been implicated in 11 additional deaths, and 86 more adverse reactions. Most of the cases involved Heparin used to clean intravenous lines. The Heparin associated with two of the 11 deaths wasn’t contaminated and the FDA is unable to conclusively say how many of the deaths and side effects involved the tainted Heparin. The FDA also did not identify which companies’ products were associated with the adverse reactions and deaths.
The Judicial Panel on Multidistrict Litigation - a seven-member panel of federal judges - ruled that all of the Baxter Heparin lawsuits nationwide would be moved to Toledo. In the ruling, Judge G. Heyburn II, of the U.S. Western District of Kentucky and chairman of the panel, wrote: "Seven of the 23 known actions are pending in this [Northern District of Ohio], mostly before Judge James G. Carr, who has the time to devote to this docket."
In addition to Baxter, many of the Heparin lawsuits scheduled to be heard in Toledo also name Scientific Protein Laboratories as a defendant.
In January, Baxter International began recalling Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC.
Tainted Heparin injections have been linked to more than 80 deaths and hundreds of adverse reactions in the U.S. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in a 12 countries. In the US, other Heparin suppliers have issued precautionary recalls, and some medical devices makers have also recalled Heparin-coated products.
Last week, the FDA said that medical devices made with Heparin had been implicated in 11 additional deaths, and 86 adverse reactions. Most of the cases involved Heparin used to clean intravenous lines. The Heparin associated with two of the 11 deaths wasn’t contaminated and the FDA is unable to conclusively say how many of the deaths and side effects involved the tainted Heparin. The FDA also did not identify which companies’ products were associated with the adverse reactions and deaths.
The FDA has advised health professionals and facilities to review and examine all drug/device storage areas — including emergency kits, dialysis units and automated drug storage cabinets — to ensure that all of the recalled Heparin products have been removed and are no longer available for patient use.
At least 11 deaths and 86 cases of harmful side effects reported this year in the US have been linked to the use of medical devices containing the blood thinner Heparin. Most of the cases involved Heparin used to clean intravenous lines, said Karen Riley, a Food and Drug Administration (FDA) spokeswoman. According to Riley, the Heparin associated with two of the 11 deaths wasn't contaminated and the FDA is unable to conclusively say how most of the other deaths and side effects involved the tainted Heparin. Riley also said that she was unable to identify which companies' products were associated with the adverse reactions and deaths.
Heparin is a blood thinner administered in surgery and other critical care areas to prevent clots, is crucial in dialysis and heart surgery, and is used for the bedridden. Heparin, which has been manufactured since 1930, is administered to millions of patients yearly and Baxter manufactures about half of all multiple-dose Heparin vials sold in the US. The FDA has reported that, since the end of 2007, it received over 700 reports of adverse reactions associated with Baxter's multiple-dose injectable Heparin; 40 percent of these reports were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock and, in 21 cases, led to death.
The ensuing investigation revealed problems regarding inadequate FDA inspections of overseas drug and drug component manufacturers and ingredients obtained from shoddy, unregulated factories. These inadequacies served to highlight some of the critical problems going on at the FDA and have led to government investigations and hearings over FDA practices.
In addition to Baxter, companies including the device make Medtronic Inc. have voluntarily recalled products that may contain contaminated Heparin. Side effects and deaths linked to medical devices occurred between January 1 and May 14, according to the FDA's Website. Since January 2007, 81 people have died after allergic reactions, the FDA said on April 21. Riley said the 11 deaths involving devices are “probably in addition'' to the 81, though some of the reports to the FDA are “very sketchy'' and there could be “some minor overlap.''
The FDA also said contamination could lead to inaccurate test results from diagnostic devices that monitor Heparin or use it as part of the device itself.
Baxter has said the main ingredient for its Heparin probably was contaminated before reaching its supplier in China.
The European Medicines Agency said today in a statement that one of its committees concluded a type of Heparin, enoxaparin, can still be used, provided that measures are taken to reduce risks. Enoxaparin was found to include a low level of contamination. Sanofi-Aventis SA's Lovenox contains enoxaparin.
In January, Baxter International began recalling Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the Food & Drug Administration (FDA) confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC.
The FDA has not determined when the chondroitin sulfate entered the Heparin supply chain, but suspicion rests on China. Changzhou used two consolidators to supply it with a raw ingredient made from pig intestines, as is chondroitin sulfate. Those consolidators obtained the ingredient from unregulated workshops. In April, FDA Commissioner Andrew von Eschenbach has said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.” The reason for the counterfeiting may have been economic. According to The New York Times, oversulfated chondroitin sulfate costs $9 a pound compared with $900 a pound for Heparin.
While the Chinese have not disputed that the chemical made its way into the Heparin at some point along its manufacturing supply chain, regulators there have insisted that the chondroitin sulfate could not have caused the adverse reactions. But the MIT study is strong evidence that such a theory is without merit.
Using lab animals - in this case pigs - the scientists found that chondroitin sulfate activates two inflammatory pathways: one that initiates blood clotting and dilation of the blood vessels, and one that produces anaphylactic toxins. The first leads to a dangerous decrease in blood pressure, the second a serious allergic reaction. In blinded laboratory tests, the contaminated Heparin activated the biological pathways, while normal Heparin did not.
The experiments also helped scientists come up with a test for detecting the chemical in Heparin. Heparin consists of a long, complex chain of repeating sugar molecules. Oversulfated chondroitin sulfate, which is derived from animal cartilage, has a structure very similar to that of Heparin and thus cannot be identified with the tests normally used to inspect batches of Heparin. Traditional Heparin safety screens test only for contaminants such as protein, lipids or DNA, and thus would not detect the presence of sugar chains that do not belong. The MIT research team played a key role in developing new technologies for analyzing complex sugars. Using the new technology, the research team was able to detect the presence of the faulty sugars.
Dennis Quaid has sued Baxter International Inc., maker of Heparin, for negligence in packaging different doses in similar vials—which contributed to the overdose—and not issuing a recall after three other infants died from a similar mix-up wherein six newborns were mistakenly overdosed.
Quaid said his twins were two weeks old when they were twice given 1,000 times the recommended dose of Baxter's Heparin while being treated for an infection. Their blood "basically turned to the consistency of water," causing massive bleeding, he said. About 40 hours later, clotting started returning to normal and they recovered, although long-term effects are unknown, Quaid said.
Quaid said victims of harm from medicines should be able to seek damages from manufacturers in state court. Drug and medical-device makers argue that U.S. Food and Drug Administration (FDA) approval should preempt state liability suits in many instances; the Supreme Court backed that view in a recent device case. "I believe if preemption of lawsuits is allowed to prevail, it will basically make all of us, the public, uninformed and uncompensated lab rats," Quaid said as he urged Congress to pass legislation to protect patients' ability to sue drugmakers if the Supreme Court further restricts the suits.
Pharmacy technicians stock Heparin for use in preventing clots and for flushing IVs. Hospital protocol is to keep the different units separated, but a technician accidentally put the 10,000 unit vials in the drawer where the 10 unit vials were stored. Baxter said the overdose resulted from human error at the hospital and was "unrelated to the safety and efficacy of Baxter's product." Baxter had revised Heparin labels before the Quaid twins were treated, but did not recall older bottles because that "may have disrupted the supply of a safe and critical medication." Baxter cited preemption in its motion to dismiss Quaid's lawsuit.
Under the current administration, the FDA advocates preemption. "FDA believes that the important decisions it makes about the safety, efficacy, and labeling of medical products should not be second-guessed by state courts," said FDA Deputy Commissioner Randall Lutter. Patients still could sue if companies sold devices that failed to meet FDA conditions of approval, he added.
Representative Henry Waxman—Democrat-California and House Oversight and Government Reform Committee chair—called the FDA's view a "radical legal doctrine" that was not in keeping with previous FDA positions and would be harmful if allowed. "One of the most powerful incentives for safety—the threat of liability—would vanish," added Waxman who said he will back legislation to reverse the Supreme Court's February ruling, which involved a New York man who was injured when a doctor inflated a Medtronic Inc. balloon catheter during an artery-clearing procedure. A similar case involving drugmaker Wyeth is expected to be heard by the high court in October.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the Food & Drug Administration (FDA) confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-thinning properties. Baxter, which supplied roughly 50 percent of the Heparin injections used in US, temporarily suspended Heparin manufacturing, and is said to be considering getting out of the business all together.
Other drug manufacturers have stepped up their production of Heparin, and the FDA says a shortage of the vital blood thinner has been avoided. Unlike the single-dose products typically distributed by Baxter, many of the vials now contain larger or more potent quantities. Pharmacists and others are reportedly worried that doctors and nurses may be unfamiliar with new packaging for Heparin, and could easily give a patient a more potent dose than intended. The concern is so great, according to an article in Newsday, that the Institute for Safe Medication Practices near Philadelphia is planning to warn about the higher risk of medication error in the next newsletter it sends to the country's 6,000 hospitals.
Even before the recent problems, Heparin overdose was a cause for concern. In February 2007, the FDA and Baxter International issued a two-page safety alert warning of the fatal dangers of mistaking high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors did not occur. The 2007 alert was issued after three infants died in Indiana when they were mistakenly given adult doses. In December 2007, actor Dennis Quaid and his wife named Baxter in a lawsuit after their newborn twins were mistakenly given potentially fatal overdoses of Heparin. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
American's first learned of the problems with Heparin in January, when Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties.
That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Recently, researchers in the US were able to show that the chondroitin sulfate could produce reactions like those seen in patients in lab animals. Last month, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
While China is the main suspect in the Heparin contamination, the FDA has no idea where the chondroitin sulfate entered the supply chain. That's because, while the FDA has been allowed to inspect Changzhou, the Chinese won't give the agency access to any of the workshops that made raw Heparin ingredients for the facility. The Chinese also won't let the FDA look at records pertaining to Heparin manufacturing and the procurement of ingredients, and the agency has also been barred from interviewing workers in Heparin manufacturing.
In spite of its obstructive attitude, the FDA seems more interested in placating the China than getting to the bottom of the Heparin mystery. For instance, citing privacy agreements, the FDA has denied Congressional investigators access to a list of firms in China that supply Heparin ingredients that was requested almost ten days ago.
The FDA is also going along with China's refusal to open up the entire Heparin supply chain for inspection. While it has barred Changzhou from importing products to the US, other manufacturers are still sending Heparin ingredients to the US. That has some lawmakers upset. Earlier this week, Rep. Bart Stupak (D-Mich.) told The Wall Street Journal that the FDA needs to be tougher on China. “If I was the FDA director, I’d shut down every drug coming in from China” until they were deemed safe, he said.
Earlier this year, Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in a 12 countries. In the US, other Heparin suppliers have issued precautionary recalls, and some medical devices makers have also recalled Heparin-coated products.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs. Last month, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
The FDA, which falls under Leavitt's authority, has been rightly criticized for its role in the Heparin debacle. Shortly after the first Heparin recall was issued, it was learned that the FDA had never inspected the Changzhou plant. Apparently, an error in the agency's compute database had made it appear as though inspectors had checked out the facility. Once the FDA did finally inspect Changzhou, it found a host of problems which it detailed in a warning letter. The FDA also banned the plant from importing to the US until corrections are made.
Leavitt told the Associated Press yesterday that the FDA has implemented tougher testing and other controls to insure the quality of the Heparin supply. "We have put in place processes that we believe can ensure the safety of the Heparin supply within the United States," he said.
Leavitt also said that he believed the US and China would soon resolve a dispute over the FDA's investigation. The Chinese so far have refused to acknowledge that chondroitin sulfate had anything to do with the Heparin reactions, despite scientific studies done in the US that demonstrated the chemical could do so. The Chinese have also not allowed the FDA access to the entire Heparin supply chain. Though it inspected the Changzhou facility in March, the FDA has been barred from having complete access to some Chinese workshops that supplied Changzhou with raw Heparin ingredients, as well as records and workers.
Several lawmakers, including Rep. Bart Stupak (D-Mich) have been critical of the FDA's failure to insist that China allow it to examine the entire Heparin supply chain. "If I was the FDA director, I’d shut down every drug coming in from China” until they were deemed safe, Stupak recently told The Wall Street Journal.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in a 12 countries. In the US, other Heparin suppliers have issued precautionary recalls, and some medical devices makers have also recalled Heparin-coated products.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs. Last month, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
Despite the publicity over tainted Heparin, it appears some medical facilities haven't gotten the message and are still stocking recalled Heparin. Last week, the FDA issued an updated Heparin warning in an attempt to make sure all medical providers are aware of the Heparin recalls. "Please help FDA spread the word about recalls of injectable Heparin products and Heparin flush solutions that may be contaminated with oversulfated chondroitin sulfate (OSCS). Affected Heparin products have been found in medical care facilities in one state since the recall announcement," the notice read. "Although product recall instructions were widely distributed, they may not have been fully acted upon at all sites where Heparin is used," it said.
The FDA's reminder was prompted by reports from California Department of Health, the FDA's own recall monitoring, and from Baxter International Inc., the largest supplier of Heparin, showing problems in the recall response. An FDA spokesperson told The Wall Street Journal that California authorities had sent a letter out on May 2 about gaps in the recall response. Inspectors checked various facilities and found recalled Heparin on crash carts, in catheter labs, and even on hospital pharmacy shelves.
Meanwhile, members of Congress have become increasingly impatient about the FDA's response to a congressional Heparin investigation. At this time, the FDA is refusing to give lawmakers access to the names of Chinese companies that supply Heparin ingredients. The FDA has said that doing so would violate privacy agreements concerning proprietary information.
Congress is also less than pleased with what appears to be Chinese attempts to block some facets of the Heparin investigation. Though it inspected the Changzhou facility in March, the FDA has been barred from having complete access to some Chinese workshops that supplied Changzhou with raw Heparin ingredients, as well as records and workers. The FDA was already under fire because, due to a compute error, it had never inspected Changzhou until the Heparin contamination became an issue. Since the March inspection, the agency has issued the factory a warning letter and barred it from importing products to the US.
But despite the Chinese reluctance to open up the entire Heparin supply chain to FDA inspection, the agency is allowing Heparin imports from that country's other manufacturers. The FDA didn't issue a blanket "import alert" legally holding up all Chinese Heparin pending successful testing, because it doesn't have the legal authority to do so, FDA officials have said.
Rep. Bart Stupak (D-Mich), the lawmaker leading the congressional investigation, told The Wall Street Journal the FDA should take a tougher stance with China. If I was the FDA director, I'd shut down every drug coming in from China" until they were deemed safe, he said.
Tainted Heparin has been of concern since January, when Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in 11 other countries, including Denmark, Italy, France Germany and Japan. In the US, Heparin has been associated with the deaths of more than 100 people since early 2007, according to the Food & Drug Administration (FDA). Of those, the vast majority - 81 to be exact - were associated with contaminated batches of Heparin.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Since then, researchers have been able to show that chondroitin sulfate can cause reactions like those seen among patients treated with tainted Heparin.
In speaking with reporters after a Senate hearing last month, FDA Commissioner Andrew von Eschenbach said that while the agency has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.” It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
According to an Atrium press release, its Heparin-coated Hydraglide Thoracic Catheters were manufactured with Heparin found to have been contaminated with oversulfated chondroitin sulfate. Atrium said in the release that the patient risk associated with the presence of the contaminant in Heparin-coated medical devices is not known at this time. Customers with affected lots are advised to immediately discontinue use of these devices and obtain replacement catheters from Atrium. So far, Atrium has not received reports of any Heparin-related injuries arising from any use of the Hydraglide Thoracic Catheters
The Atrium Hydraglide recall follows last week's medical device recall by Medtronic. That recall involved a variety of disposable medical devices, used during cardiac bypass surgery, that are made with Medtronic’s Carmeda BioActive surface, which includes Heparin. Both recalls were initiated because of an April 8 recommendation by the FDA that medical devices made be subjected to a new method of testing to insure that the drug was not contaminated with chondroitin sulfate.
Tainted Heparin first garnered attention earlier this year, when Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in 11 other countries, including Denmark, Italy, France Germany and Japan. In the US, Heparin has been associated with the deaths of more than 100 people since early 2007, according to the Food & Drug Administration (FDA). Of those, the vast majority - 81 to be exact - were associated with contaminated batches of Heparin.
In March, the FDA confirmed that it had found chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Since then, researchers have been able to show that chondroitin sulfate can cause reactions like those seen among patients treated with tainted Heparin.
In speaking with reporters after a Senate hearing last month, FDA Commissioner Andrew von Eschenbach said that while the agency has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.” It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
Medtronic says the Carmeda BioActive surface is used on blood oxygenators, reservoirs, pumps and other disposable products that are used during the bypass surgery. According to Reuters, Medtronic initiated the recall because of an April 8 recommendation by the FDA that medical devices employing Heparin be checked with newly-developed tests to make sure the Heparin is not tainted. Chondroitin sulfate cannot be identified with the tests normally used to inspect batches of Heparin.
A separate Medtronic line of disposable bypass-surgery products covered with a different biosurface called Trillium will remain on the market because they incorporate far smaller amounts of Heparin.
The US Food & Drug Administration (FDA) has linked tainted Heparin with 81 deaths in the US, and hundreds of adverse reactions. Baxter International recalled nearly all its Heparin injections in the U.S. after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Last month, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
In a written statement, China's State Food and Drug Administration insisted that the chondroitin sulfate had nothing to do with the adverse Heparin reactions. The Chinese assert that since contaminated Heparin has been found in 12 countries, and reactions have only been seen in the US and Germany, the chemical is not to blame. The statement also claims reactions have also been reported in people who received untainted Heparin.
The statement also claimed that "Baxter failed to provide necessary cooperation in the process of the investigation, which is not conducive to further identifying the reasons for the adverse reactions to Heparin." Baxter is denying these allegations, and says it is cooperating with all parties in the Heparin investigation. Last month, Chinese regulators were even given access to Baxter's New Jersey plant where it finishes processing raw Heparin.
The Chinese assertion that chondroitin sulfate was not behind the Heparin reactions is questionable. Late last month, a research team, led by scientists at MIT, found that the chondroitin sulfate activates two inflammatory pathways: one that initiates blood clotting and dilation of the blood vessels, and one that produces anaphylactic toxins. The first leads to a dangerous decrease in blood pressure, the second a serious allergic reaction. In blinded laboratory tests, the contaminated Heparin activated the biological pathways, while normal Heparin did not. In the study, pigs treated with tainted Heparin exhibited side effects similar to those seen in humans.
In March, the FDA confirmed that it had found a counterfeit ingredient, oversulfated chondroitin sulfate, in samples of the active ingredient used in Baxter Heparin. The chemical had been molecularly changed to mimic Heparin's blood thinning properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. Since then, companies in several other countries have issued Heparin recalls, and a cluster of Heparin reactions has been reported in Germany. In the US, some other manufacturers have issued precautionary recalls.
Due to a computer error, the FDA never inspected the Changzhou plant as is required by law. When Heparin problems finally prompted the agency to conduct an inspection, it found a multitude of problems. The FDA has since issued Changzhou a warning letter, and it has been barred from exporting to the US until corrections are made.
The FDA has not determined when the chondroitin sulfate entered the Heparin supply chain, but suspicion rests on China. Changzhou used two consolidators to supply it with a raw ingredient made from pig intestines, as is chondroitin sulfate. Those consolidators obtained the ingredient from unregulated workshops. Earlier this month FDA Commissioner Andrew von Eschenbach has said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.” The reason for the counterfeiting may have been economic. According to The New York Times, a Congressional investigator said oversulfated chondroitin sulfate, cost $9 a pound compared with $900 a pound for Heparin.
Yesterday, Dr. Janet Woodcock, director of the FDA’s drug center, told the House Subcommittee on Oversight and Investigations in written testimony that a third of the ingredient found in some batches of Heparin contained contaminant. She said the agency was working on the hypothesis that the contamination was intentional, although that has yet to be proven.
Robert L. Parkinson, Baxter’s chairman and chief executive, concurred with Dr. Woodcock. He 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.”
Lawmakers also heard from the family members of patients who died after being administered tainted Heparin. 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,” Hubley said, breaking down in tears. “Then my wife and love of 48 years drifted away.” Hubley said it was weeks before he found out that either death was due to contaminated Heparin.
Last week, the FDA said it had evidence that the chondroitin sulfate did, in fact, cause the reactions and deaths. However, the Chinese are disputing this, and say the Heparin problems could have originated in the US. David G. Strunce, chief executive of Scientific Protein Laboratories, said that his company tried to find the original source of the contamination but was stopped by the Chinese authorities.
In March, the Food & Drug Administration (FDA) confirmed that it had found a counterfeit ingredient, oversulfated chondroitin sulfate, in samples of the active ingredient used in Baxter Heparin. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. Since then, companies in several other countries have issued Heparin recalls, and a cluster of Heparin reactions has been reported in Germany. In the US, some other manufacturers have issued precautionary recalls.
The FDA has not determined when the chondroitin sulfate entered the Heparin supply chain, but suspicion rests on China. Changzhou used two consolidators to supply it with a raw ingredient made from pig intestines, as is chondroitin sulfate. Those consolidators obtained the ingredient from unregulated workshops. FDA Commissioner Andrew von Eschenbach has said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
Last week, the FDA said it had evidence that the chondroitin sulfate did, in fact, cause the reactions and deaths. However, the Chinese are disputing this, and say the Heparin problems could have originated in the US. But an FDA inspection of Changzhou uncovered a number of problems, and earlier this month, the FDA issued the plant a warning letter, calling the facility "unsuitable". The FDA has also blocked Changzhou from importing anything to the US until the agency can confirm it has made appropriate corrections.
Starting tomorrow, a US House of Representatives Subcommittee on Oversight and Investigations will hold a hearing called "The Heparin Disaster: Chinese Counterfeits and American Failures," the latest congressional proceeding to address shortcomings in the US inspection process. Baxter CEO Robert Parkinson will testify, along with FDA drug unit chief Janet Woodcock. Also slated to testify is the CEO of Scientific Protein Labs.
Meanwhile, some media reports have suggested that Baxter is considering giving up the Heparin business altogether. Earlier this month, Wall Street analysts asked Parkinson whether it was worth the legal risks and liability to remain in the business given that Heparin accounts for only $30 million of Baxter's more than $11 billion in annual sales. Parkinson said that the company had not yet decided if it would reenter the Heparin market.
"This is a loophole that must be closed," Padilla said, adding that the Chinese SFDA does not have the authority to simultaneously regulate pharmaceutical makers of active pharmaceutical ingredients and makers of bulk chemicals which may be used in pharmaceuticals but not considered of medicinal use. "The rapid growth of China's economy has clearly outstripped the ability and the will of the government to effectively police that economy," Padilla said. Padilla, who is leading a group of healthcare executives to China, also said effective monitoring was a part of larger healthcare reforms that mainland authorities were handling.
This week, U.S. researchers from the Massachusetts Institute of Technology (MIT) identified a chemical contaminating the blood-thinner Heparin from China, revealing how it could cause a sometimes-fatal allergic reaction. The tainted Heparin was used by at least 81 U.S. patients who later died, forcing Heparin maker Baxter International to recall the drug and causing diplomatic strain between the U.S. and China.
Healthcare services and products are one of the United States' fastest growing exports to China; reforms could include anything from basic state-funded health insurance to enhancements in how it provides healthcare and primary care and regulates hospitals, according to Padilla. "I have a new-found respect for the enormity of the challenge that China faces in the healthcare reform effort," he said.
Disputes between patients and hospitals are common in China, where market reforms of the 1980s ended lifelong healthcare and inadequate monitoring has lead to overcharging, bogus treatments, and corruption. For instance, earlier this year, one of China’s largest state-owned pharmaceutical company’s—exporter to dozens of countries, including the U.S.—was at the center of a nationwide drug scandal after nearly 200 Chinese cancer patients were paralyzed or harmed by contaminated leukemia drugs. Chinese drug regulators accused the manufacturer—Shanghai Hualian—of a cover-up and closed the factory that produced them. In December, China’s Food and Drug Administration said that Shanghai police began a criminal investigation. And, in China's harshest action, thus far, the country's former top drug regulator was executed for accepting millions of dollars in bribes to approve substandard medicines, including an antibiotic that killed at least 10 people.
China could unveil its health service plan this year. It is expected that the plan will institute universal medical coverage paid for by insurance rather than general taxation. "It won't happen this year," said Rachel Lee, a principal for The Boston Consulting Group based in Shanghai. "Foreign investors are very interested in China, but the problems are also very large," she said.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found a counterfeit ingredient, oversulfated chondroitin sulfate, in samples of the active ingredient used in Baxter Heparin. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. So far, 81 deaths in the U.S. have been linked to the tainted Heparin, and earlier this week, the FDA said it had evidence that the chondroitin sulfate did, in fact, cause the reactions and deaths.
The FDA conducted an inspection of Changzhou SPL in March. According to the strongly-worded warning letter to the factory dated April 21, conditions there were deemed "unsuitable" by the FDA. The agency said that the Changzhou provided no assurance that processing steps used to manufacture Heparin ingredients were capable of effectively removing impurities. The letter also stated that Changzhou had acknowledged to the FDA that it received and used Heparin crude materials from a workshop that Changzhou itself had deemed as "unacceptable" in a "pre-audit". Even though that workshop was ultimately not approved to be a supplier to the facility, Changzhou used crude material from this workshop in the production of Heparin ingredients that were shipped to the U.S.
In addition, the FDA warning letter to Changzhou SPL said that the testing methods employed by the facility were not " verified to ensure suitability under actual conditions of use," and that equipment used at the factory to make Heparin ingredients was "unsuitable for its intended use".
The FDA has given Changzhou SPL 30 days to respond to the charges in the letter. Until the FDA is able to confirm that Changzhou has corrected violations at the factory, and certify that it now meets Current Good Manufacturing Practice standards, all products made there will be denied entry to the U.S.
The Food & Drug Administration (FDA) has linked tainted Heparin with 81 deaths in the US, and hundreds of illnesses. Baxter International recalled nearly all its Heparin injections in the U.S. after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
The New England Journal of Medicine study, led by researchers at MIT, offers the first potential link between the contaminant and the adverse reactions. The researchers found that the chondroitin sulfate activates two inflammatory pathways: one that initiates blood clotting and dilation of the blood vessels, and one that produces anaphylactic toxins. The first leads to a dangerous decrease in blood pressure, the second a serious allergic reaction. In blinded laboratory tests, the contaminated Heparin activated the biological pathways, while normal Heparin did not.
The researchers also said that regulators now have a test to detect contaminated Heparin. Heparin consists of a long, complex chain of repeating sugar molecules. Oversulfated chondroitin sulfate, which is derived from animal cartilage, has a structure very similar to that of Heparin and thus cannot be identified with the tests normally used to inspect batches of Heparin. Traditional Heparin safety screens test only for contaminants such as protein, lipids or DNA, and thus would not detect the presence of sugar chains that do not belong. The MIT research team played a key role in developing new technologies for analyzing complex sugars. Using the new technology, the research team was able to detect the presence of the faulty sugars.
According to The New York Times, the FDA has identified 12 Chinese companies that have supplied contaminated Heparin to 11 countries — Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand and the United States. The FDA has not determined the original source of all the contamination or the points in the supply chain at which it was added. The Times also said officials have discovered tainted Heparin lots that were manufactured as early as early as 2006, although a spike in illnesses associated with contaminated Heparin began in November and persisted through February.
The FDA has linked tainted Heparin with 81 deaths in the US, and hundreds of adverse reactions. Baxter International recalled nearly all its Heparin injections in the U.S. after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
But at a news conference earlier this week, a Chinese official disputed that the Heparin problems occurred in that country. Jin Shaohong, deputy director-general of the China National Institute for the Control of Pharmaceutical and Biological Products, said that Chinese investigators tested batches of Heparin used by patients who reported health problems, and only some contained chondroitin sulfate. He also said that Heparin with the contaminant has been found in many nations, but that none has reported a similar spike in harmful reactions as in the United States. Shaohong also said Chinese officials are focusing on the whole product, and speculated that other contaminants, problems with the device used to inject the Heparin, or health factors with the patients who used the drug could also be causing the reactions.
But the FDA countered, saying a cluster of adverse reactions to Heparin has been reported in Germany. Evidence is also growing that implicates the chondroitin sulfate in the US reactions. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research said that Chinese officials had tested batches of Heparin with methods less sensitive than those used in the US and elsewhere and had missed the presence of the contaminant. She said FDA scientists now believe the adverse reactions were most pronounced when large doses of the drug were administered quickly, and the contaminant acted as a "mediator" that caused a response similar to an allergic reaction.
According to The New York Times, the FDA has identified 12 Chinese companies that have supplied contaminated Heparin to 11 countries — Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand and the United States. The FDA has not determined the original source of all the contamination or the points in the supply chain at which it was added. The Times also said officials have discovered Heparin lots that included the cheap fake additive manufactured as early as early as 2006, although a spike in illnesses associated with contaminated Heparin began in November and persisted through February.
The Chinese inspectors finished their tour of Baxter's plant yesterday. So far, neither the Chinese nor Baxter will comment on the inspection.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted Heparin has been identified in a 12 countries.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
Due to computer error, the FDA never inspected the Chinese plant where raw ingredients for Baxter Heparin were made. When Heparin problems finally prompted the agency to conduct an inspection, it found a multitude of problems, including:
- Incomplete manufacturing instructions
- Lack of critical processing steps or annual test results
- Lack of an impurity profile for Heparin
- Incomplete manufacturing instructions for Heparin Sodium USP
- Investigations into failed lots were approved as complete, but no cause was listed
- Inadequate control of material flow in the processing area
Yesterday, a warning letter from the FDA to the Chinese factory was released. In the letter, the FDA said its inspection of the Chinese facility two months ago revealed "significant deviations" from US good manufacturing practices. In addition, the FDA said the plant's processing steps used to manufacturing Heparin's active ingredient provided "no assurance" any impurities could have been effectively removed.
Scientific Protein Laboratories responded to the letter by claiming it does reflect Changzhou SPL's "actual state of compliance". The company also said the contaminant was introduced earlier in a supply chain. Changzhou buys its crude Heparin from two companies, called consolidators, that gather it from workshops that make it from pig intestines. Many Chinese workshops that make crude Heparin are unregulated family operations. Those workshop were apparently never inspected by the FDA either.
The FDA has linked tainted Heparin with 81 deaths in the US, and hundreds of adverse reactions. Baxter International recalled nearly all its Heparin injections in the U.S. after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
According to The New York Times, the FDA has identified 12 Chinese companies that have supplied contaminated Heparin to 11 countries — Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand and the United States. The FDA has not determined the original source of all the contamination or the points in the supply chain at which it was added. The Times also said officials have discovered Heparin lots that included the cheap fake additive manufactured as early as early as 2006, although a spike in illnesses associated with contaminated Heparin began in November and persisted through February.
Meanwhile, Baxter International confirmed that tests had shown that the chondroitin sulfate could cause illness, but disputed the FDA assertion that tainted Heparin was associated with 81 deaths. Baxter's own numbers indicate only 5 deaths linked with Heparin, and the company insists that the tainted drug may have only "contributed" to, rather than caused, the fatalities.
Yesterday, Jin Shaohong, deputy director-general of the China National Institute for the Control of Pharmaceutical and Biological Products, insisted that problems with Heparin sold by Baxter originated in the U.S. He also insisted that there was no proof the chondroitin sulfate was responsible for the problems. Shaohong told reporters at a news conference that the Chinese were planning to send inspectors to Baxter's New Jersey plant to see if the problems started there.
Another Chinese official, Ning Chen, second secretary at the Chinese Embassy, told The Times that, “We don’t have a strong evidence to show that it is Heparin or its contaminant that caused the problem." Chen insisted that Heparin reactions had only been seen in the US, indicating that neither the chondroitin sulfate or Chinese manufacturing was at fault.
But Dr. Janet Woodcock, director of the FDA's drug center, disputed Chen, pointing out that a cluster of Heparin reactions had been reported in Germany, and that China had conceded that the drug involved in those reactions was contaminated. She also said the FDA was "fairly confident" that the chondroitin sulfate was capable of causing the adverse Heparin reactions seen in the past year.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In the US, Heparin has been associated with the deaths of more than 100 people since early 2007, according to the Food & Drug Administration (FDA). Of those, the vast majority - 62 to be exact - were associated with contaminated batches of Heparin.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
However, the Chinese are disputing that the chondroitin sulfate has anything to do with the Heparin injuries seen in the US. Shaohong said that Chinese investigators tested batches of Heparin used by patients who reported health problems, and only some contained chondroitin sulfate. "The oversulfated chondroitin can therefore not be the suspected root cause of Heparin ADE (adverse events)," he told reporters at a news conference this morning.
Shaohong also said Chinese officials are focusing on the whole product and planned to visit Baxter's plant in New Jersey later on Monday. "They will cooperate with us, no problem," he told reporters. Shaohong speculated that other contaminants, problems with the device used to inject the Heparin, or health factors with the patients who used the drug could also be causing the reactions.
Despite Shaohong's insistence that Chinese manufacturing is blameless in the Heparin debacle, counterfeit ingredients have caused problems with Chinese imports in the past. The news of Heparin contamination came almost one year after some pets in the US died as the result of a pet food ingredient shipped from China that contained toxic levels of melamine, which was added to make it appear higher in protein. In Panama around the same time, 120 people died because an unlicensed Chinese chemical plant sold a cheap counterfeit ingredient, diethylene glycol, that was mixed into cold medicine imported to that country. Diethylene glycol contamination also resulted in a recall of Chinese-made toothpaste in the US over the summer.
China has also made efforts to crack down on Heparin producers since it became apparent that something had gone wrong with the drug. According to a report in The Wall Street Journal, the Chinese State Food and Drug Administration issued an order in a notice seen on its Web site that requires Heparin producers to obtain the raw chemicals used to make the drug from registered suppliers. Raw Heparin suppliers, meanwhile, are required to improve their management and tests on their products, it said. This was a reversal of the Chinese government’s earlier position, as the agency had earlier insisted that ensuring the quality of exported chemicals like Heparin was the responsibility of importers and importing countries.
Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced Heparin in Denmark, Italy, France Germany and Japan. In the US, Heparin has been associated with the deaths of more than 100 people since early 2007, according to the FDA. Of those, the vast majority - 62 to be exact - were associated with contaminated batches of Heparin.
In March, the FDA confirmed that it had found chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. It costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs. In speaking with reporters after a Senate hearing, von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, "the concern is that it had to be by design."
If so, it would not be the fist time Chinese products were the subject of fraudulent ingredient substitutions. In fact, the news of Heparin contamination came almost one year after some pets in the US died as the result of a pet food ingredient shipped from China that contained toxic levels of melamine, which was added to make it appear higher in protein. In Panama around the same time, 120 people died because an unlicensed Chinese chemical plant sold a cheap counterfeit ingredient, diethylene glycol, that was mixed into cold medicine imported to that country. Diethylene glycol contamination also resulted in a recall of Chinese-made toothpaste in the US over the summer.
The Baxter Heparin recalls came after the blood thinner was linked to hundreds of extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. Other manufactures have conducted similar recalls of Heparin in Denmark, Italy, France Germany and Japan. In the US, several other companies, including B. Braun, American Health Packaging and Covidien Ltd. announced precautionary recalls of Heparin products.
In March, the FDA confirmed that it had found chondroitin sulfate in samples of the active ingredient used in Baxter Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties. However, the agency has not yet determined if the chondroitin sulfate was responsible for the deaths and reactions associated with Heparin, although the chemical is the prime suspect.
Baxter gets some of that active ingredient from Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. The FDA said it had found contaminated crude Heparin at that plant. Changzhou buys its crude Heparin from two companies, called consolidators, that gather it from workshops that make it from pig intestines. Many workshops that make crude Heparin in China are unregulated family operations.
Since the contaminant was discovered, the FDA has been detaining all Heparin imports at the border for testing before they are allowed into the US. The FDA has also now sent a letter to drug device manufacturers warning them to examine the sources of the Heparin used in their products, as some drug devices, particularly vascular stents and other devices used in pulmonary bypass, as well as in-vitro diagnostic procedures, are coated with a small amount of Heparin.
The FDA has yet to determine how and where the chondroitin sulfate entered the Heparin supply chain in China, which is now the largest supplier of raw Heparin ingredients in the world.