In 2008, Baxter International recalled prefilled Heparin vials after they were linked to serious, and sometimes fatal, allergy-type reactions in some patients. There were similar recalls by other manufacturers in Denmark, Italy, France, Germany, and Japan. In total, tainted Heparin was identified in 12 countries. It was eventually determined that a counterfeit ingredient in Chinese-sourced Heparin was to blame for the problems.
According to a notice on the FDA's Web site, in response to the contamination problems, the United States Pharmacopeia (USP), a nonprofit standards-setting organization, has adopted new manufacturing controls for Heparin to ensure the quality and to guard against potential contamination. These changes include a modification of the reference standard for the drug’s unit dose, the FDA said. The revised USP reference standard and unit definition for Heparin is about 10 percent less potent than the former USP unit.
The change in Heparin potency may have clinical significance in some situations, such as when Heparin is administered as a bolus intravenous dose and an immediate anticoagulant effect is clinically important, the FDA said. In such situations, the agency said healthcare providers should consider the change in potency of Heparin when making decisions about what dose to administer. The change in Heparin potency is expected to be less clinically significant when it is administered subcutaneously due to the low and highly variable bioavailability of Heparin when administered by this route. Healthcare providers should also be aware of the decrease in Heparin potency as they monitor the anticoagulant effect of the drug; more Heparin may be required to achieve and maintain the desired level of anticoagulation in some patients.
While the USP manufacturing controls take effect Oct. 1 for production, the FDA has asked manufacturers that they not ship this new product to customers until Oct. 8, 2009, or later. The delay will give health care providers and facilities time to learn about the changes and to make adjustments to their pharmacy procedures and dosing practices, the agency said. It has also asked that all manufacturers identify their new products to help pharmacies and health care professionals differentiate it from the former product.
Four companies market Heparin in the United States. APP, the largest manufacturer, markets Heparin in vials; Hospira markets Heparin in intravenous bags, vials, and syringes; Baxter markets Heparin in intravenous bags, and B. Braun markets Heparin in intravenous bags.
Baxter International says the quality of its Heparin was not to blame for serious complications in three patients at a Delaware medical center last week. According to Baxter, product testing has cleared its blood thinner.
The incidents - which involved two fatalities - had re-ignited fears about potentially tainted Heparin. In 2008, Baxter recalled prefilled Heparin vials after they were linked to serious, and sometimes fatal, allergy-type reactions in some patients. There were similar recalls by other manufacturers in Denmark, Italy, France, Germany, and Japan. In total, tainted Heparin was identified in 12 countries.
It was eventually determined that a counterfeit ingredient in Chinese-sourced Heparin was to blame for the problems. The Centers for Disease Control (CDC) ultimately identified 152 adverse reactions associated with Heparin in 113 patients from November 19, 2007 through January 31, 2008. What’s more, the agency said Heparin manufactured by Baxter “was the factor most strongly associated with reactions.”
Baxter hasn't made Heparin vials since the 2008 recall. The patients involved in the incidents at Delaware's Beebe Medical Center received Heparin from pre-mixed IV bags. According to the Associated Press, unlike the Heparin involved in the recall, the active ingredient for the Heparin the Beebe patients received was supplied by Pfizer. The pre-mixed bags were finished at Baxter's plant in Puerto Rico.
The three patients at Beebe suffered intracranial bleeding. They all had to be airlifted to nearby medical centers, and two died. The Food & Drug Administration (FDA) and officials from Baxter had been at Beebe throughout the week investigating the incidents.
Today, Baxter released a statement that said intracranial bleeding the patients suffered “was related to underlying medical conditions and risk factors.” The statement said the Heparin "performed exactly as intended, and … the events were not related to a quality product issue."
According the Associated Press, the FDA is expected to release a statement on the Beebe Heparin investigation soon.
Two of five patients sickened after being treated with Heparin at Beebe Medical Center in Delaware have died, prompting the Food & Drug Administration to launch an investigation. According to the Chicago Tribune, the Heparin IV bags all five patients received were supplied by Baxter International.
The incident has once again raised concerns over the safety of Heparin, which caused hundreds of serious reactions and some deaths in late 2007 and 2008. Baxter Heparin, some of which was tainted with a counterfeit ingredient, was subject to a massive recall at the time.
The Baxter IV Heparin bags used in the Delaware incidents are a diluted form of the drug that are supplied in pre-mixed bags and used for a number of “blood-thinning purposes,” said the Tribune. Use of the drug has been suspended at Beebe Medical Center following the reports of adverse reactions in five patients, which included internal bleeding in the brain. Three of the patients had to be airlifted to other medial centers—one to Christiana Care Health System, and two to the University of Maryland Hospital. Two other patients did recover after being monitored at Bebe.
Two of the patients died, according to The Wall Street Journal. One patient was 71-year-old man and, the other, a 64-year-old woman. A spokesman for Beebe Medical Center confirmed the deaths.According to Erin Gardiner, a Baxter spokeswoman, the side effects in the current cases involved intracranial bleeding and not low blood pressure (hypotension), reported the Journal. Low blood pressure was one of the hallmark reactions to the tainted Heparin in 2007- 2008.
In early 2008, Baxter issued a massive recall of Heparin products after patients treated with the drug suffered serious and, in some cases, fatal side effects. There were similar recalls by other manufacturers in Denmark, Italy, France, Germany, and Japan with tainted Heparin identified in 12 countries. In the US, the FDA ultimately initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies.
Baxter and the other Heparin manufacturers obtained raw ingredients for Heparin from processors in China. In March 2008, the FDA confirmed that it had found over-sulfated 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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and Chinese producers may have used it in an attempt to cut costs.
It was eventually confirmed by the Centers for Disease Control (CDC) that the chondroitin sulfate was to blame for the Heparin side effects. The CDC ultimately identified 152 adverse reactions associated with Heparin in 113 patients from November 19, 2007 through January 31, 2008. What’s more, the agency said Heparin manufactured by Baxter “was the factor most strongly associated with reactions.”
For now, officials at Beebe Medical Center are not saying that the Heparin involved in the sickened patients was tainted, only that the outcomes are “unusual.” Baxter said that the Heparin involved with the two patient deaths originated form a North American-derived bulk material supplied by Pfizer Inc., reported the Journal.
"We are not pointing fingers at Baxter," said Beebe Medical Center spokesman Wallace Hudson. "We don't know what's going on, but Heparin is the only commonality that we were able to see ourselves," quoted the Journal.
As we reported over the weekend, an independent lab is testing the Baxter Heparin used at Beebe, though it is not known when those tests will be complete.
Smart People filmFears over tainted Heparin re-emerged this weekend, as reports surfaced that five patients at a Delaware medical center suffered serious complications on Friday, following the administration of pre-mixed bags of Heparin. According to officials at Beebe Medical Center in Lewis, Delaware, the Heparin was supplied by Baxter International Corp.
According to the Web site delmarvanow.com, three patients treated with the Baxter Heparin suffered internal bleeding. However, tests on two others with similar symptoms ruled out internal bleeding. Three of the patients had to be airlifted to other medial centers - one to Christiana Care Health System, and two to the University of Maryland Hospital. The remaining patients were monitored at Beebe, but have recovered. Similar reactions have not been reported in any other Beebe patients, delmarvanow.com said.
A spokesperson for Beebe told delmarvanow.com that the medical center would conduct an investigation to determine what was behind the patients' side effects. As part of the probe, samples of the Heparin were sent to an outside lab for analysis. However, it is not known when results of tests will be available.
For now, use of all Heparin products has been suspended at Beebe. Officials from Baxter were also reportedly at the medical center on Saturday to assist with an examination of the incident.
In early 2008, Baxter issued a massive recall of Heparin products after patients treated with the drug suffered serious - and in some cases fatal - side effects. There were similar recalls by other manufacturers in Denmark, Italy, France, Germany and Japan. In total, tainted Heparin was identified in 12 countries. In the US, the Food & Drug Administration (FDA) ultimately initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies. The Tooth Fairy hd Bone Trouble film
Baxter and the other Heparin manufacturers obtained raw ingredients for Heparin from processors in China. In March 2008, 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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and Chinese producers may have used it in an attempt to cut costs.
It was eventually confirmed by the Centers for Disease Control (CDC) that the chondroitin sulfate was to blame for the Heparin side effects. The CDC ultimately identified 152 adverse reactions associated with Heparin in 113 patients from Nov. 19, 2007 through Jan. 31, 2008. What's more, the agency said Heparin manufactured by Baxter “was the factor most strongly associated with reactions."
For now, officials at Beebe Medical Center are not charging that the bags of Heparin given to the five patients were tainted. They will only say that the outcomes seen are "unusual". Beebe officials have notified the FDA and the Delaware Health Care Operations Center of the unusual Heparin reactions.
download Ten Dead MenAn official for Baxter told delmarvanow.com that the premixed bags of Heparin administered to the five Beebe patients were not part of last year's recall, and were made after the previous problems with Heparin had been reported. The Baxter spokesperson also told the Web site that the company had not received similar reports from other medical centers.
The MedXL syringes subject to the warning involves those with lot numbers between 6892 and 8180. It includes the following catalog numbers: 3704, 37043, 37043B, 37043BNC, 3705C, 3705NC, 3706, 3780, 3781, 3786 and 3787.
According to the safety notice, the probability of a clinician finding a defective syringe of this type in a lot of products is extremely small (approximately 12 defective syringes per million syringes manufactured). However, clinicians in Canada are being reminded to take the following precautions to avoid the accidental use of a defective prefilled syringe:
* Use aseptic technique.
* Visually inspect product for particulate matter and discoloration prior to use
* Do not use if the solution is discolored or contains a precipitate.
According to Health Canada, there have been no reports so far of adverse reactions linked to the defective MedXL syringes. MedXL has implemented the necessary corrective actions to correct this problem, the agency said.
Anyone with questions regarding the syringe safety alert can contact MedXL at 514-695-7474 ext 103 or 514-695-7474 ext 139.
In January 2008, Baxter International recalled nearly all its Heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, after being administered the products. There were 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, the FDA ultimately initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies.
In March 2008, 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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
According to The Wall Street Journal, the FDA has now charged that Qingdao Jiulong Biopharmaceuticals Co. and Shanghai No. 1 Biochemical & Pharmaceutical Co. were involved in making and sending 19 lots of tainted Heparin sodium to the U.S., which the agency discovered in April 2008. The tainted drug didn't reach any patients because the FDA stopped all the shipments at the border, the Journal said. The FDA said the Heparin had been contaminated with oversulfated chondroitin sulfate.
The charges were included in letters the FDA sent to the firms following inspections conducted in July and August 2008. In its letter to Shanghai No. 1, the FDA also said it "uncovered untrue statements and information by your firm to the agency" relating to the actual maker of Heparin.
The FDA letters said the firms have in the past supplied Heparin to California-based Amphastar Pharmaceuticals Inc., and its subsidiary International Medication Systems Ltd. According to The Wall Street Journal, Amphastar makes pre-filled syringes and other products.
This is the first time the FDA has disclosed that Qingdao Jiulong and Shanghai No. 1 had been implicated in the tainted Heparin scandal, the Journal said. At a Congressional hearing last March, the FDA would only identify Changzhou SPL, even though it had said at least 12 Chinese companies had been implicated.
Heparin is a blood thinner, and the vital drug is used in surgery, dialysis, and to prevent blood clots in the bedridden. Other drugs thin blood, but do not work as quickly as Heparin, and their effects are not as easily reversed. Baxter International manufactures about half of the multi-dose Heparin vials used in the US.
The dosing error made by nurses at Cedars-Sinai landed the babies in critical condition and with the potential to bleed out, said the LA Times, which also said that although the hospital was not sued, it was described in legal paperwork as “potential defendant." According to the LA Times piece, Cedars-Sinai hospital “officials have cited at least three safety lapses that led to the overdoses”; the Wall Street Journal also stated that an internal inquiry at the Cedars-Sinai revealed the incident involved three separate safety lapses.
The Quaid’s suit against Baxter alleges that it was the drug’s labeling and design which led to what the LA Times described as a “massive overdose,” noting that—in the suit—Baxter knew other babies had died from similar dosing errors but did not recall the “high-concentration vials.” The Wall Street Journal added that while Baxter redesigned its Heparin packaging, it should have, but did not, recall the unused, higher dosage vials. Baxter claims, said the Wall Street Journal, that the hospital is at fault.
In response to the medical error, the Quaid’s have launched a Website, entitled The Quaid Foundation, devoted to reducing such preventable medical errors: http://thequaidfoundation.org/. The Foundation’s site notes that the error that caused the babies’ illness was a result of a variety of “human errors” that involved the drug manufacturer, the hospital pharmacy, the pediatric ward, and the administering nurse. The Quaid’s noted that the nurse gave two, separate and massive Heparin doses to the infants over an eight-hour period. The Quaid’s also noted the Heparin debacle that was linked to the death of three infants in Indianapolis.
In February 2007, the Food & Drug Administration (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 addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
This past January, 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. The FDA eventually identified 93 deaths and hundreds of adverse reactions following Heparin administration were reported between January 1, 2008 and March 31, 2008, although cause of death was uncertain in 45 of these deaths.
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, the FDA initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies
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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
According to the new CDC study, the agency has identified 152 adverse reactions associated with Heparin in 113 patients from Nov. 19, 2007 through Jan. 31, 2008. The CDC said that Baxter Heparin was present in 100.0% of case facilities versus 4.3% of control facilities.
“Of 130 reactions for which information on the Heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated Heparin on the premises. Of 54 reactions for which the lot number of administered Heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated Heparin,” the study said.
The CDC investigation included testing unopened Heparin vials from 21 dialysis facilities that reported reactions and 23 facilities that reported no reactions.
Heparin was the subject of a major product recall after a potentially lethal contaminant was identified and traced to suppliers in China. Last January, 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, the FDA initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies.
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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
In his letter to the GAO, Barton, the ranking Republican on the House Energy and Commerce Committee, expressed concern about conflicting statements the FDA made to the public and Congress about the number of deaths tied to contaminated batches of Heparin. In particular, Barton said he had concern about the FDA’s classification of the deaths of three patients. The letter cites a Chicago Tribune article where it was reported that the FDA “conclusively linked” the deaths of those patients to a foreign substance found in specific lots of Baxter Heparin.
However, in his letter, Barton maintains that in a response to his questions about those deaths, the "FDA classified the cause of death from Heparin as only ‘possible’ in two of those cases, and ‘unassessable’ in the third case.”
Barton’s letter to the GAO also questions whether the FDA used all of the tools available to conduct comprehensive surveillance of the Heparin deaths. “FDA confirmed to the committee’s Republican staff that the agency did not follow up to interview clinical staff or Baxter for further details about each of these cases,” the letter says. “In addition, FDA told staff the agency did not access other databases, even though FDA has testified that such databases enhance FDA’s ability to evaluate drug safety problems.”
Heparin was the subject of a major product recall after a potentially lethal contaminant was identified and traced to suppliers in China. In the first quarter of 2008, the FDA received 779 reports of serious injury in which Heparin was the principal suspect drug, including 102 deaths.
In January, 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, the FDA initiated 13 recalls of multiple contaminated medical products containing Heparin from several companies
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. Chondroitin sulfate costs a fraction of the ingredient usually used in Heparin, and producers may have used it in an attempt to cut costs.
Since the Heparin recalls, the FDA has implemented an inspection and import controls program and has acted to remove contaminated Heparin products from the market. sulfate. The seized Celsus Heparin – which had entered the United States before the establishment of import controls for the drug – was tested for the presence of chondroitin sulfate as part of this effort.
According to an agency press release, the FDA informed Celsus Laboratories during an April 2008 inspection and again in a May 8, 2008, letter that the company's actions to notify customers about a contaminant in its Heparin were insufficient to assure an effective recall.
At the FDA's request, U.S. Marshalls seized 11 lots of Heparin from Celsus. This included five lots of Heparin Sodium Active Pharmaceutical Ingredient (API) and six lots of Heparin Lithium.
An API is a substance or mixture of substances that, when delivered in a finished drug product, directly affects the structure or function of the body. Heparin Sodium USP is an API that may be incorporated into finished drug products. Heparin Lithium is used in certain medical devices including vacutainer blood collection tubes, some in vitro diagnostic assays, and as a coating for capillary tubes. According to the FDA, Celsus has distributed Heparin Sodium USP and Heparin Lithium to manufacturers in both the U.S. and abroad.
The agency is advising manufacturers who may have purchased Heparin from Celsus to contact the company to make certain they are not using any Heparin from the seized lots because the product does not meet acceptable quality standards.
The FDA said it has also notified Japanese, Canadian, Australian, European Union, and other international authorities of shipments of contaminated Heparin from Celsus.
Two drugs accounted for what the AP termed a “disproportionately large share of the latest reports.” One drug was Heparin, the tainted blood thinner from China that caused an international safety scandal that, according to the ISMP study, accounted for 779 reports of serious problems, including 102 deaths. The FDA, which relies on data spanning a longer time frame, reports 238 deaths possibly linked to Heparin.
The other drug was Chantix, a new anti-smoking drug from Pfizer that has been blamed for a number of unusual and dangerous reactions and works in the brain to both ease withdrawal symptoms and block the pleasurable effects of nicotine when a smoker attempts to light up. Chantix received the most reports of any medication. The FDA should forcefully warn patients taking Chantix that they might suffer blackouts and other problems that could lead to accidents, the report said. The report found 15 cases of traffic accidents, and 52 additional cases involving blackouts or loss of consciousness in Chantix patients; the FDA received 1,001 reports of serious injuries, possibly linked to Chantix, represnting more than for the ten best-selling brand name drugs combined.
Chantix "continued to provide a striking signal of safety issues that require investigation and action," the report said. Meanwhile, we have long been reporting on the bizarre reactions Chantix users have been experiencing and, earlier this year, the FDA warned that Chantix may be linked to psychiatric problems, including suicidal behavior and vivid dreams. Although the government has banned Chantix for pilots, Pfizer said yesterday "We stand by the efficacy and safety profile of Chantix."
The FDA had no immediate response to the report, but defines serious drug reactions as ones that cause hospitalization, require medical intervention, or place a life in jeopardy; its monitoring system relies on voluntary reports from doctors. Many believe the system only captures a small percentage of actual cases.
The report also stated that the 20,745 cases reported from January-March was 38 percent higher than the average for the previous four calendar quarters, and the highest for any quarter, said the AP. Twenty-three percent—4,824—ended in death, a nearly three percent increase from the last calendar quarter of 2007. Previous ISMP research revealed that serious drug safety problems reported to the FDA increased significantly from 1998-2005.
“FDA case reports provide a signal of possible problems with a drug, but a cause-and-effect connection can only be established through painstaking investigation,” reported the AP. For instance, if “the FDA were a police agency, the reports would indicate ‘probable cause,’ but not necessarily ‘guilt beyond a reasonable doubt,’” the AP pointed out. As far as Chantix is concerned, many feel that reasonable doubt has been met.
In the past year and a half, imports from China have been at the center of safety worries in the US and other countries. Earlier this year, Heparin contaminated with a counterfeit ingredient was implicated in dozens of deaths in the US, and hundreds of serious reactions both here and abroad. In the past month, the FDA has issued recalls of several foods imported from China that may have been tainted with the industrial chemical melamine. Melamine tainted dairy products have hospitalized thousands of children in that country.
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. A recent report from the Government Accountability Office (GAO) found that, on average, foreign drug plants are inspected only once every 13 years.
The opening of a Beijing, China office later this year is just the first step in the FDA's plan to expand its presence overseas. According to the Associated Press, staff posted at the China office will inspect facilities, provide guidance on U.S. quality standards, and eventually train local experts to conduct inspections on behalf of the FDA. The FDA will eventually open offices in the Chinese cities of Shanghai and Guangzhou.
China has not been the only country sending questionable imports to the US This year, peppers from Mexico were implicated in one of the largest salmonella outbreaks in US history, and the FDA recently banned Indian generic drug maker Ranbaxy from importing drugs.
Over the next year, the agency plans to place 60 food and drug regulators in offices worldwide, focusing on India, Latin America and the Middle East. According to the Associated Press, the plan would cost about $30 million in its first year, primarily to set up the offices and hire new staffers, including foreign nationals who would report to the agency.
But even FDA Commissioner Andrew von Eschenbach and Health and Human Services Secretary Mike Leavitt, whose department oversees the FDA, acknowledge the agency will still have too few inspectors to adequately police every foreign manufacturer that sends products to the U.S. According to the Associated Press, they are hoping to solve that problem by allowing a voluntary inspection, where manufacturers would pay third-party inspectors to verify that their plants meet FDA standards.
Beside the obvious conflict-of-interest problems posed by manufacturers paying a for-profit service for their own inspections, many doubt that the FDA will convince overseas companies to participate. Similar attempts at a voluntary inspections system haven't been well received in the past by overseas manufacturers. To counter that problem, the FDA says it would offer those manufacturers that do agree to such a program expedited entry for their products at US ports.
But such a program would require the approval of Congress, and many members have expressed skepticism that it would work. Democrats in the House of Representatives, for example, have a proposed a program that would require companies to pay mandatory user fees to help finance additional FDA inspections.
Measures could include, for example, bar-coding technology for medicines or computerized drug orders. The Commission also advised hospitals to more closely monitor patients on these drugs and ensure adult-strength Heparin is stored nowhere near children's Heparin units. The alert also mentioned that “28 deaths are among 32 reports of drug errors involving blood thinners that it received between 1997 and last year,” the AP said. "We know that there are many more (deaths) and ... that's the reason for issuing this alert," said Dr. Mark Chassin, president of the Commission. The commission is a private group that sets hospital standards and accredits most of the nation's hospitals. “Accreditation brings prestige and federal dollars,” the AP explained.
Heparin is the drug involved in Dennis Quaid's twins’ overdose this past autumn at Cedars-Sinai Hospital in Los Angeles, California. In July, 14 babies received accidental Heparin overdoses at a hospital in Corpus Christi, Texas. In February 2007, the Food and Drug Administration (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 inventory to ensure dispensing errors did not occur and was issued after three infants died in Indiana when they were mistakenly given adult doses.
According to US Pharmecopia, during the prior 18 months, there were roughly 250 medical errors nationwide involving Heparin and children a year or younger. This year, tainted Heparin has been implicated in 149 deaths and hundreds of allergy-type reactions. The firm, which sets drug standards, stated in the alert that a total of 59,316 medication errors involving blood thinners were reported between 2001 and 2006 to its database. Nearly three percent, or about 1,700 of the errors resulted in patient harm or death. In March, the FDA confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Heparin linked to the scandal involving China-manufactured Heparin for Baxter International.
As part of its measures, Commission investigators will make unannounced visits to ensure hospitals are adopting strict procedures to prevent blood thinner-related errors. Those who fail to make such changes could have their accreditation revoked, Chassin said. Chassin explained that the challenge with blood thinners is that too much can cause hard-to-control bleeding internally and from every body opening, while not enough can cause life-threatening blood clots. Heparin is usually given intravenously. Warfarin, another blood thinner cited in the alert, is available in pills patients can take at home, but Warfarin can cause negative reactions when mixed with other medicines.
The AP piece also mentioned that James Conway, senior vice president of the nonprofit Institute for Healthcare Improvement in Cambridge, Massachusetts felt that the recommendations "absolutely" will make a difference and hospitals will pay attention. Time will tell.
Conventional Heparin is often made in small workshops in China, which contributes to contamination, according to Linhardt, who is a professor of chemistry, biology, and chemical engineering at Rensselaer Polytechnic Institute in Troy, New York. "Our group has been working on understanding Heparin biosynthesis for almost 30 years," he said. "We are working on what might be the next generation of Heparin production, with no animal source." Pig intestines are the traditional manufacturing source for Heparin.
Although synthetic Heparin has been made in the recent past, it was only manufactured in microscopically small amounts. Linhardt is scheduled to speak Sunday at the American Chemical Society annual meeting, in Philadelphia and described a new method of Heparin biosynthesis that has produced amounts measured in milligrams. Linhardt hopes that production can be dramatically increased. The process starts with a polysaccharide, a chain of carbohydrate units, extracted from the bacterium E. coli. "We treat it to reduce the molecular size, then subject it to enzymatic steps to convert it to Heparin," he explained. "We use recombinant enzymes that are part of the natural pathway for Heparin synthesis." The challenge is in "scaling up the process so it is commercially viable," Linhardt said. "We are now working with one liter amounts. There are million-liter fermenters. We have to scale up three orders of magnitude, which is pretty daunting but not impossible."
Heparin is administered via injection and is used to prevent blood clotting during heart surgery, kidney dialysis, and other procedures. With a fully synthetic form of Heparin, the sort of contamination seen this past year would be a thing of the past, Linhardt said. Linhardt’s group received funding from the U.S. National Institutes of Health (NIH). "It's too early to approach a pharmaceutical company," he said. "We have talked to a number of them. They all are interested in the approach but want to wait."
Linhardt said he is aware that there are several drugs designed to replace not only Heparin, but also the widely used clot-preventing medication Coumadin. Such medications are in clinical trials in Europe, with some already approved for medical use. "I won't deny there's competition," Linhard said. "But those drugs are a thousand times more expensive than Heparin. Also, they are not as good as Heparin. It has multiple activities, many of which benefit patients. Those drugs are very specific. They work well only for a small number of applications." Synthetic Heparin could cost no more than the animal-derived product, Linhardt said. "We believe that the Heparin market is here to stay," he said.
Meanwhile, in March, the Food and Drug Administration (FDA) confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter-supplied Heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties and was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories.
On July 8, the hospital announced an investigation to determine the cause of the "preventable medication error." Also on July 8, Keith Garcia died; Kaylynn died the next day. Hospital officials claim they have not discovered anything to indicate the Garcia twins died as a result of the Heparin overdose. But, Keith and Kaylynn’s parents, in collaboration with parents of other affected babies, have hired attorneys to investigate if the overdose caused injuries to their babies and resulted in the twins’ deaths.
One of the attorneys representing several families in the Heparin cases, said he has already had several Heparin samples collected from the hospital and that the purpose for today’s hearing is for the judge to decide what evidence he wants preserved, in case lawsuits seeking damages are filed. Twenty samples of the same Heparin believed to have been accidentally given to the babies was collected from Christus Sphon South last week. The attorney feels the Heparin samples and other medical evidence will enable them to determine if the babies were injured because of the overdose and will clarify how much Heparin the babies were given. The Garcia family attorney also had samples collected from the hospital and said the Garcia’s may be called to testify today.
Heparin is the drug involved in Dennis Quaid's twins’ overdose this past autumn at Cedars-Sinai Hospital in Los Angeles, California. In that case, the Heparin was made by Baxter Healthcare. Christus Spohn Hospital South said its Heparin was not made by Baxter, but would not say who manufactured it because the mistake was a mixing error.
In February 2007, the Food and Drug Administration (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 inventory to ensure dispensing errors did not occur and was issued after three infants died in Indiana when they were mistakenly given adult doses. According to US Pharmecopia, during the past 18 months, there have been roughly 250 medical errors nationwide involving Heparin and children a year or younger.
This year, tainted Heparin has been implicated in149 deaths and hundreds of allergy-type reactions. In March, the FDA confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Heparin supplied by Baxter. The FDA said the chondroitin sulfate was molecularly changed to mimic Heparin’s blood-clotting properties and 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 may have been substituted to cut costs.
In January, 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.
In April, 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.
According to an article in The Chicago Tribune, the FDA said it completed its review of 93 death reports related to Heparin that the agency received from Jan. 1 to March 31, when reports of Heparin adverse reactions peaked. Of 10 reports of death from severe anaphylaxis or hypotension, three of those could be traced to lot numbers of Baxter products that tested positive for chondroitin sulfate. Heparin lot numbers were not known for the other seven deaths, so the FDA could not determine if those patients received tainted Heparin.
Of the remaining 83 reports, the FDA described 13 as "potential complications of Heparin use" such as bleeding; 25 cases were due to causes unrelated to Heparin use such as pneumonia, sepsis and kidney failure. The FDA said that there was insufficient information available about the remaining 45 fatalities to conclusively cite a cause of death.
Quaid's twins, born November 8, recovered from a Heparin overdose this autumn at Cedars-Sinai Hospital in Los Angeles, California. Quaid said his twins fell ill with staph infections, suffering the overdose November 18. The babies were administered 1,000 times the correct dose. Heparin concentrates are bottled with similar labels and size, an issue long debated. Quaid said that when rotated slightly, the light blue 10-unit bottle and the dark blue10,000-unit bottle are difficult to distinguish from each other.
Quaid called the incident "a nightmare to live through…. At the beginning there was a lot of anger, shock, and fear." Quaid has turned his anger into “a desire to raise awareness about medical errors in medications and formed The Quaid Foundation, according to the AP. "We certainly don't blame the nurse, but everybody makes mistakes," he said. "It was just a breakdown." According to the AP, a January report from the California Department of Public Health said Cedars-Sinai did not adequately educate staff about safe use of Heparin and nurses sometimes failed to adequately read labels on Heparin vials.
Meanwhile, 14 babies were recently overdosed at Christus Spohn Hospital South after pharmacy workers made what the hospital called a Heparin "mixing error." Two of the babies—born one month premature—died; however, the hospital claims its physicians have found no direct links to the overdose. Autopsies are being underway.
In February 2007, the Food and Drug Administration (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 inventory to ensure dispensing errors did not occur and was issued after three infants died in Indiana when they were mistakenly given adult doses. According to US Pharmecopia, during the past 18 months, there have been roughly 250 medical errors nationwide involving Heparin and children a year or younger. This year, tainted Heparin has been implicated in 149 deaths and hundreds of reactions. In March, the FDA confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Heparin supplied by Baxter International; the ingredient was molecularly changed to mimic Heparin’s blood-clotting properties. The 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.
Heparin, an anticoagulant used to clean intravenous tubes and prevent blood from clotting in the lines, is the drug involved in Dennis Quaid's twins’ overdose this past autumn at Cedars-Sinai Hospital in Los Angeles, California. In that case, the Heparin was made by Baxter Healthcare. Christus Spohn Hospital South said the Heparin used in its case was not made by Baxter, but would not say who manufactured it because the mistake was a mixing error, not a confusion of bottle labels.
Spokeswoman Sherry Carr-Deer confirmed 14 babies received a more concentrated dose of Heparin than prescribed saying, "We know for sure, we know absolutely for sure, that there were 14 babies who got the concentrated Heparin," Carr-Deer said. She said three other babies were in the unit when the higher doses were given, but could not confirm if those babies were overdosed. The other babies who received a higher-than-prescribed dose of Heparin remain in critical but stable condition at the hospital, Carr-Deer said. According to standard procedure, nurses were supposed to clean the infants' IV lines with Hep-Lock, a drug containing a very small dose—10 units—of Heparin. Instead, the twins received 10,000 units, or 1,000 times the prescribed amount.
A judge approved the Garcia family’s attorney’s request for a temporary restraining order directing the hospital to save medication, documents, lab results, and vials involved in the babies' care. "We haven't filed a lawsuit seeking damages, just trying to find out what happened," the attorney said. He said he plans to ask the court to let him take depositions from hospital personnel. "The babies were roughly four weeks' premature and should not have been at high risk. The doctor assured the parents the newborns' lungs were fully developed, he added.
In February 2007, the Food and Drug Administration (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 inventory to ensure dispensing errors did not occur and was issued after three infants died in Indiana when they were mistakenly given adult doses. According to US Pharmecopia, during the past 18 months, there have been roughly 250 medical errors nationwide involving Heparin and children a year or younger. Also, this year tainted Heparin has been implicated in 149 deaths and hundreds of allergy-type reactions. In March, the FDA confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Heparin supplied by Baxter International. 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.
Heparin is a blood thinner that is routinely used in the hospital neonatal intensive care units to flush intravenous lines and prevent blood clots from forming. Unfortunately, Heparin overdoses are a common medical mistake. In February 2007, the Food & Drug Administration (FDA) and Baxter International, once a major supplier of Heparin, 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. According US Pharmecopia, during the past 18 months, there have been roughly 250 medical errors nationwide involving Heparin and children a year or younger.
According to the Houston Chronicle, the Heparin first was administered in the Corpus Christi hospital's neonatal intensive care unit Friday. A nurse discovered the overdose on Sunday, during routine blood testing. The use of Heparin in the unit was discontinued, and the infants were given medication to counteract the Heparin's effects. One infant remains in critical condition in the unit, and was in that condition for several days before the Heparin dosages, the Chronicle said. Three infants have been discharged and 12 are stable and remain in intensive care.
Two members of the Christus Spohn Hospital South's pharmacy staff have taken voluntary leave, pending an investigation that could take as long as two weeks. The hospital has also notified the Texas Department of Health Services and the FDA of the incident.
Recently, Heparin has sparked concerns for reasons other than accidental overdoses. This year, tainted Heparin has been implicated in 149 deaths and hundreds of allergy-type reactions. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Heparin supplied by Baxter International. 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.
According to the FDA, it has now received reports of 248 deaths among people who had taken Heparin since January 1, 2007. Of those, 238 were reported to the FDA on or after January 1, 2008. Among the fatalities, 149 involved patients who suffered allergic reactions known to be associated with tainted Heparin. 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.
Whatever the cause, the 248 deaths since January 2007 indicate a significant increase in Heparin-related fatalities compared with the prior year. Between January 1, 2006 and December 31, 2006, there were only 55 reported deaths following the administration of Heparin - about 4 or 5 per month. Most of the patients in these reports were suffering from a variety of underlying medical conditions, on in only 3 cases did deaths occur following an allergy-type reactions.
The spike in allergic-type reactions - including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening - following administration of Heparin prompted Baxter International to recall nearly all of its Heparin injections in the US earlier this year. 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.
In April, 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.
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.