In a word, whom do you blame? The manufacturer, for sourcing the tainted heparin from China in the first place? Or the government, for not providing the US Food and Drug Administration (FDA) with the necessary tools to police imports? In Missouri, they’re suing the manufacturer — in this case, for allegedly waiting too long to initiate a recall.

The family of the late Freddie James Williams Sr. is suing Tyco Healthcare, one of the last companies to initiate a heparin recall after reports began pouring in that something was decidedly wrong with heparin coming in from a certain factory in Changzhou, China. Between January 17 and March 21 of this year, three other healthcare companies announced four recalls of heparin products originating from Changzhou SPL, a facility majority-owned by Scientific Protein Laboratories of Wisconsin.

Tyco Healthcare finally recalled its heparin stocks on March 28th. However, the recall came too late for Mr. Williams, 67, who died the same day. The lawsuit launched on his behalf — believed to be the first action against Tyco Healthcare — is being handled by Jeffrey Killino, a name familiar to regular readers of Lawyers&Settlements.com. “Public and medical professionals need to be extremely cautious,” says the lawyer from Philadelphia.

“This case demonstrates that recalled heparin is still in circulation, and there may be many more deaths throughout the country linked to it. The family was never notified of the recall, and one month after Freddie’s death, his family still has numerous recalled syringes in their possession.

“No one has contacted them to ensure those syringes were discarded.”

The situation first raised its head in November of last year, when the Missouri Department of Health and Senior Services began to analyze an outbreak of acute allergic reactions amongst a handful of adult and pediatric hemodialysis patient. Once State officials alerted the US Centers for Disease Control and Prevention (CDCP) in Atlanta on January 7, 2008 things began to happen quickly. A nationwide alert for similar cases revealed that two dialysis supply companies reported at least 50 similar allergic reactions among adult hemodialysis patients at facilities in several States.

The heparin scare now encompasses nine countries, and the tainted heparin has been found to be contaminated with oversulfated chondroitin sulfate (OCS), an over-the-counter medication for the treatment of joint pain. OCS is produced at a fraction of the cost of pure heparin, mimics heparin, and is impossible to detect using standard testing methods. The tainted heparin has been linked to the Changzhou SPL plant in China, which has been cited by the FDA for several violations at the American-owned plant. Among them, failure to control its crude supplies, to test for impurities, to investigate the cause of failed lots and for manufacturing with unclean tanks containing unidentified materials.

The facility in question supplied heparin to all four companies which initiated recalls. Baxter, one of the largest producers of heparin that sourced raw heparin through the Changzhou SPL plant was the first to respond to the concern and issue a recall, coming on January 17th — just over a week after Missouri State health officials notified the CDCP and within days, if not hours of realizing the problem was more widespread than first thought.

Baxter not only shut down its heparin manufacturing facility in response to the concern in early February, it also triggered a recall of its heparin lock flush syringes on February 28th. A little less than a month later, on March 20th and 21st two more heparin companies issued recalls: American Health Packaging, and B. Braun Medical announced recalls of their heparin products.

Had Tyco Healthcare done the same, or earlier, would Williams be alive today? That’s a question for the courts. Tyco waited until March 28th to announce a recall, the day Mr. Williams died. A few days could have made a big difference, and might have saved Mr. Williams from the pain and suffering he experienced while going through what amounted to be the classic symptoms of heparin contamination: nausea, vomiting, excessive sweating and extremely low blood pressure.

Symptoms he could have been spared, and a life that could have been saved.

In a word, whom do you blame? The manufacturer, for sourcing the tainted heparin from China in the first place? Or the government, for not providing the US Food and Drug Administration (FDA) with the necessary tools to police imports? In Missouri, they’re suing the manufacturer — in this case, for allegedly waiting too long to initiate a recall.

The family of the late Freddie James Williams Sr. is suing Tyco Healthcare, one of the last companies to initiate a heparin recall after reports began pouring in that something was decidedly wrong with heparin coming in from a certain factory in Changzhou, China. Between January 17 and March 21 of this year, three other healthcare companies announced four recalls of heparin products originating from Changzhou SPL, a facility majority-owned by Scientific Protein Laboratories of Wisconsin.

Tyco Healthcare finally recalled its heparin stocks on March 28th. However, the recall came too late for Mr. Williams, 67, who died the same day. The lawsuit launched on his behalf — believed to be the first action against Tyco Healthcare — is being handled by Jeffrey Killino, a name familiar to regular readers of Lawyers&Settlements.com. “Public and medical professionals need to be extremely cautious,” says the lawyer from Philadelphia.

“This case demonstrates that recalled heparin is still in circulation, and there may be many more deaths throughout the country linked to it. The family was never notified of the recall, and one month after Freddie’s death, his family still has numerous recalled syringes in their possession.

“No one has contacted them to ensure those syringes were discarded.”

The situation first raised its head in November of last year, when the Missouri Department of Health and Senior Services began to analyze an outbreak of acute allergic reactions amongst a handful of adult and pediatric hemodialysis patient. Once State officials alerted the US Centers for Disease Control and Prevention (CDCP) in Atlanta on January 7, 2008 things began to happen quickly. A nationwide alert for similar cases revealed that two dialysis supply companies reported at least 50 similar allergic reactions among adult hemodialysis patients at facilities in several States.

The heparin scare now encompasses nine countries, and the tainted heparin has been found to be contaminated with oversulfated chondroitin sulfate (OCS), an over-the-counter medication for the treatment of joint pain. OCS is produced at a fraction of the cost of pure heparin, mimics heparin, and is impossible to detect using standard testing methods. The tainted heparin has been linked to the Changzhou SPL plant in China, which has been cited by the FDA for several violations at the American-owned plant. Among them, failure to control its crude supplies, to test for impurities, to investigate the cause of failed lots and for manufacturing with unclean tanks containing unidentified materials.

The facility in question supplied heparin to all four companies which initiated recalls. Baxter, one of the largest producers of heparin that sourced raw heparin through the Changzhou SPL plant was the first to respond to the concern and issue a recall, coming on January 17th — just over a week after Missouri State health officials notified the CDCP and within days, if not hours of realizing the problem was more widespread than first thought.

Baxter not only shut down its heparin manufacturing facility in response to the concern in early February, it also triggered a recall of its heparin lock flush syringes on February 28th. A little less than a month later, on March 20th and 21st two more heparin companies issued recalls: American Health Packaging, and B. Braun Medical announced recalls of their heparin products.

Had Tyco Healthcare done the same, or earlier, would Williams be alive today? That’s a question for the courts. Tyco waited until March 28th to announce a recall, the day Mr. Williams died. A few days could have made a big difference, and might have saved Mr. Williams from the pain and suffering he experienced while going through what amounted to be the classic symptoms of heparin contamination: nausea, vomiting, excessive sweating and extremely low blood pressure.

Symptoms he could have been spared, and a life that could have been saved.

It was revealed, according to a report in the New York Times, that the FDA has now identified a clear link between the heparin contaminant oversulfated chondroitin sulfate–found in various lots of heparin inbound from China–and adverse reactions that have, according to the FDA, led to deaths.

And while Baxter International, one of many heparin suppliers that have undertaken massive recalls of heparin in recent weeks disputes that figure–suggesting that the number is closer to 5–there is little doubt that the heparin scare is the widest-ranging incident so far, pointing to the qualitative quotient of products imported into the United States and other nations, from China.

And worse, the drugs on which we rely to remain healthy, to avoid sickness, to stay alive.

In reality, they may be contributing to our demise.

In the very latest developments, the FDA sent a warning letter to Changzhou SPL on Monday. That’s the American-owned plant located in China that appears to be at the center of the contaminated heparin crisis. The agency cited the plant for having used unclean tanks to make heparin, lacking adequate processes for removing impurities, and accepting raw materials from unacceptable vendors.

To that end the FDA has so far identified 12 companies in China that have supplied tainted heparin, although the agency concedes that it does not know the original source of all the contamination, or the points in the supply chain through which the contaminant was added.

The latter would take a Herculean effort to nail down, given the huge cottage industry in China of small, mom-and-pop heparin huts where workers in sweatshop conditions process raw heparin fashioned from the mucous membrane of pig intestines. There are literally thousands of such unregulated enterprises spread across several provinces in China.

So far, countries affected beyond the US include Canada, Germany, Denmark, France, Italy, Japan, New Zealand, the Netherlands, Australia and China itself.

It has since been determined that the heparin contaminant oversulfated chondroitin sulfate (OCS) had been showing up as early as 2006. However, with only a few deaths linked to adverse reaction to heparin, the alarm bells were mute until a spike of heparin deaths began in November of last year and continued until this past January.

Oversulfated chondroitin sulfate is a substance derived from shellfish that is used as an oral treatment for joint pain. However, it has remarkable similarities to heparin as to its chemical makeup–hence its use as a counterfeit to bolster the content of real heparin. Why this was done, is anyone’s guess but speculation abounds. OCS comes in at a fraction of the cost of real heparin, and escapes detection when standard testing procedures are used. An outbreak of blue ear pig disease last year in many of China’s provinces depleted stocks, and is said to have driven prices up. The heparin counterfeiting also fits a previous profile with regard to past misdeeds, including adding melamine (plastics) to pet food to bolster protein readings, diethylene glycol (anti-freeze) to mimic pharmaceutical glycerin in toothpaste and cough syrup, and toxic leaded paint in children’s toys.

In other words, to save a buck.

While the motive has yet to be established and the issue is still at play, Congress is in the midst of trying to figure out how to fix this problem, and deal with what’s inevitably bound to keep coming down the Great Wall if procedures are not put in place now. Congressional hearings are scheduled for today in the House, and Thursday in the Senate.

The Government Accountability Office is set to release a report today suggesting that the FDA would need to spend $56 million more in 2009 to commence full inspection of foreign plants, and would need to spend $15 million annually to inspect all drug plants in China importing to the United States–every other year.

The agency’s own failure to inspect the Changzhou SPL plant prior to approving the facility for heparin production in 2004, is a telling example of the need for a drastic infusion of more money to hire inspectors. However so far the Bush Administration, while acknowledging the problem and claiming to have strategies in hand for improving the situation, has been reluctant to advance any new funding.

“Even the Bush administration seems to understand the potential peril that these foreign firms pose,” said Representative John D. Dingell, a Michigan Democrat who leads the House Committee on Energy and Commerce, in comments published this morning in the New York Times. “But they offer only vague plans to address the problems and they refuse to spend more than a fraction of the money needed to protect the public.”

The FDA has since unveiled plans to open inspection offices in three cities in China, but have yet to receive approval from the Chinese government. In fact, China is pushing back, suggesting, “we don’t have strong evidence to show that it’s heparin or its contaminate that caused the problem,” according to comments attributed to Ning Chen, second secretary at the Chinese Embassy.

The Chinese have also suggest that inspections be reciprocal; in other words, for the US to be approved for inspection offices in China, the latter would wish for the same right in the United States.

Meanwhile, the FDA suggests there is little doubt that the contaminate found in tainted heparin, a blood thinner used commonly for dialysis and some surgical procedures, is the root for the adverse reactions which is thought to have contributed to 81 deaths now.

“Heparin should not be contaminated, regardless of whether or not that contamination caused acute adverse events,” said Dr. Janet Woodcock, director of the Food and Drug Administration’s drug center. “We are fairly confident based on the biological information that we have had that this contaminant is capable of triggering these adverse reactions.”

Baxter International concurs; noting that its own tests confirmed that the oversulfated chondroitin sulfate found in heparin could cause illness.

Meanwhile Scientific Protein Laboratories, based in Wisconsin, issued a statement suggesting that the company, and its satellite facility Changzhou SPL regretted the action taken by the FDA to issue a warning letter, and stressed that the allegations contained in the warning letter do not reflect the company’s current safety practices.

The Chinese have since agreed to test heparin lots before they leave the country for export, although the fear is that testing may not be sophisticated enough to detect a counterfeit, as was the case with the current recalled lots of product. And while the FDA assures that all current supplies of heparin in the United States have been stringently tested and deemed free of contaminants, the fear of what is to come remains.

The recent Tibetan protests in tandem with the arrival of the Beijing Olympic games, and the fact that China admits to executing it’s former chief drug official last July, is a telling snapshot of a country with which the US is doing increased business.

And so far, the Bush Administration’s reluctance to infuse the FDA with more cash to counter such crises that constitute a real threat to American safety appears curious in light of the current need. With present resources, the FDA would require 13 years to properly do a once-over of every foreign drug plant, 27 years to inspect every offshore medical device plant, and 1900 years to check out every foreign food plant.

Think about it. If you have experienced a heparin reaction, or have lost a loved one allegedly to tainted heparin, who lies at fault? The drug maker? China? Or an administration that has allowed manufacturers to shift production to foreign shores and away from American workers, without equipping its federal regulator with sufficient resources to properly police the process.

Your lawyer will help sort that one out.

It was revealed, according to a report in the New York Times, that the FDA has now identified a clear link between the heparin contaminant oversulfated chondroitin sulfate–found in various lots of heparin inbound from China–and adverse reactions that have, according to the FDA, led to deaths.

And while Baxter International, one of many heparin suppliers that have undertaken massive recalls of heparin in recent weeks disputes that figure–suggesting that the number is closer to 5–there is little doubt that the heparin scare is the widest-ranging incident so far, pointing to the qualitative quotient of products imported into the United States and other nations, from China.

And worse, the drugs on which we rely to remain healthy, to avoid sickness, to stay alive.

In reality, they may be contributing to our demise.

In the very latest developments, the FDA sent a warning letter to Changzhou SPL on Monday. That’s the American-owned plant located in China that appears to be at the center of the contaminated heparin crisis. The agency cited the plant for having used unclean tanks to make heparin, lacking adequate processes for removing impurities, and accepting raw materials from unacceptable vendors.

To that end the FDA has so far identified 12 companies in China that have supplied tainted heparin, although the agency concedes that it does not know the original source of all the contamination, or the points in the supply chain through which the contaminant was added.

The latter would take a Herculean effort to nail down, given the huge cottage industry in China of small, mom-and-pop heparin huts where workers in sweatshop conditions process raw heparin fashioned from the mucous membrane of pig intestines. There are literally thousands of such unregulated enterprises spread across several provinces in China.

So far, countries affected beyond the US include Canada, Germany, Denmark, France, Italy, Japan, New Zealand, the Netherlands, Australia and China itself.

It has since been determined that the heparin contaminant oversulfated chondroitin sulfate (OCS) had been showing up as early as 2006. However, with only a few deaths linked to adverse reaction to heparin, the alarm bells were mute until a spike of heparin deaths began in November of last year and continued until this past January.

Oversulfated chondroitin sulfate is a substance derived from shellfish that is used as an oral treatment for joint pain. However, it has remarkable similarities to heparin as to its chemical makeup–hence its use as a counterfeit to bolster the content of real heparin. Why this was done, is anyone’s guess but speculation abounds. OCS comes in at a fraction of the cost of real heparin, and escapes detection when standard testing procedures are used. An outbreak of blue ear pig disease last year in many of China’s provinces depleted stocks, and is said to have driven prices up. The heparin counterfeiting also fits a previous profile with regard to past misdeeds, including adding melamine (plastics) to pet food to bolster protein readings, diethylene glycol (anti-freeze) to mimic pharmaceutical glycerin in toothpaste and cough syrup, and toxic leaded paint in children’s toys.

In other words, to save a buck.

While the motive has yet to be established and the issue is still at play, Congress is in the midst of trying to figure out how to fix this problem, and deal with what’s inevitably bound to keep coming down the Great Wall if procedures are not put in place now. Congressional hearings are scheduled for today in the House, and Thursday in the Senate.

The Government Accountability Office is set to release a report today suggesting that the FDA would need to spend $56 million more in 2009 to commence full inspection of foreign plants, and would need to spend $15 million annually to inspect all drug plants in China importing to the United States–every other year.

The agency’s own failure to inspect the Changzhou SPL plant prior to approving the facility for heparin production in 2004, is a telling example of the need for a drastic infusion of more money to hire inspectors. However so far the Bush Administration, while acknowledging the problem and claiming to have strategies in hand for improving the situation, has been reluctant to advance any new funding.

“Even the Bush administration seems to understand the potential peril that these foreign firms pose,” said Representative John D. Dingell, a Michigan Democrat who leads the House Committee on Energy and Commerce, in comments published this morning in the New York Times. “But they offer only vague plans to address the problems and they refuse to spend more than a fraction of the money needed to protect the public.”

The FDA has since unveiled plans to open inspection offices in three cities in China, but have yet to receive approval from the Chinese government. In fact, China is pushing back, suggesting, “we don’t have strong evidence to show that it’s heparin or its contaminate that caused the problem,” according to comments attributed to Ning Chen, second secretary at the Chinese Embassy.

The Chinese have also suggest that inspections be reciprocal; in other words, for the US to be approved for inspection offices in China, the latter would wish for the same right in the United States.

Meanwhile, the FDA suggests there is little doubt that the contaminate found in tainted heparin, a blood thinner used commonly for dialysis and some surgical procedures, is the root for the adverse reactions which is thought to have contributed to 81 deaths now.

“Heparin should not be contaminated, regardless of whether or not that contamination caused acute adverse events,” said Dr. Janet Woodcock, director of the Food and Drug Administration’s drug center. “We are fairly confident based on the biological information that we have had that this contaminant is capable of triggering these adverse reactions.”

Baxter International concurs; noting that its own tests confirmed that the oversulfated chondroitin sulfate found in heparin could cause illness.

Meanwhile Scientific Protein Laboratories, based in Wisconsin, issued a statement suggesting that the company, and its satellite facility Changzhou SPL regretted the action taken by the FDA to issue a warning letter, and stressed that the allegations contained in the warning letter do not reflect the company’s current safety practices.

The Chinese have since agreed to test heparin lots before they leave the country for export, although the fear is that testing may not be sophisticated enough to detect a counterfeit, as was the case with the current recalled lots of product. And while the FDA assures that all current supplies of heparin in the United States have been stringently tested and deemed free of contaminants, the fear of what is to come remains.

The recent Tibetan protests in tandem with the arrival of the Beijing Olympic games, and the fact that China admits to executing it’s former chief drug official last July, is a telling snapshot of a country with which the US is doing increased business.

And so far, the Bush Administration’s reluctance to infuse the FDA with more cash to counter such crises that constitute a real threat to American safety appears curious in light of the current need. With present resources, the FDA would require 13 years to properly do a once-over of every foreign drug plant, 27 years to inspect every offshore medical device plant, and 1900 years to check out every foreign food plant.

Think about it. If you have experienced a heparin reaction, or have lost a loved one allegedly to tainted heparin, who lies at fault? The drug maker? China? Or an administration that has allowed manufacturers to shift production to foreign shores and away from American workers, without equipping its federal regulator with sufficient resources to properly police the process.

Your lawyer will help sort that one out.

An FDA spokesperson assures that “we’re not talking about a large amount” of heparin, in such devices. Still, amidst revelations that as much as 50 percent of the active ingredient of heparin inbound from China has been substituted with a counterfeit ingredient, one has to wonder about the long-term effects to constant exposure.

A week ago the FDA announced that deaths linked to tainted heparin from China have tripled, from 19 to 62 since January of last year. In contrast, there were just three deaths due to allergic reactions to heparin in all of 2006.

In the last several weeks, the media has been awash in recall reports. First it was Baxter International–one of the largest suppliers of heparin in the US–followed by B Braun Medical Inc., then Covidien on March 28th.

German manufacturer RotexMedica GmbH recalled batches of Chinese-produced heparin after reports of 80 allergic reactions. There have been no deaths reported so far in Germany. In March, the European Medicines Agency reported that health authorities in Denmark, France and Italy have also recalled heparin in their respective jurisdictions, as a precaution. Japan, too.

At the center of the heparin crisis is a newly-identified counterfeit ingredient that has found its way into the heparin sourced from China: oversulfated chondroitin sulfate, a derivative of animal or shark cartilage taken as a food supplement by patients experiencing joint pain. In response to the spike in adverse reactions (800 reports so far) and patient deaths linked to the blood thinner, the FDA utilized more sophisticated testing.

That’s when the oversulfated chondroitin sulfate was discovered. Why it was found in heparin is unclear. However, it has been reported that the substance is seven times less expensive than pure heparin, while impersonating heparin so well from a chemical standpoint that it’s hard to spot.

One can imagine the motive, given past indiscretions on the part of Chinese suppliers involving pet food, toothpaste, children’s toys and cough medicine. The latter was responsible for the deaths of 93 people in Central America, many of them children, a year ago.

Heparin, refined from the mucous membranes of pigs, has been around for decades and is used as a blood thinner for various procedures, including dialysis and some surgeries.

It should be noted that heparin used to be made primarily in the US and Europe. However, over the last two decades production has shifted to low-cost, developing countries.

“We have an increasingly globalized supply chain,” said James Shen, publisher of the industry newsletter Pharma China, in an Associated Press news report. “The Chinese are now major suppliers of bulk pharmaceuticals and also supply intermediate chemicals for drugs.

“It is likely we will continue to see the same problems with other drugs,” he added.

So far the facility in China at the center of the crisis, Changzhou SPL near Shanghai, has not been shown to be the actual source for the contaminant. In other words, the oversulfated chondroitin sulfate got into the supply chain before it arrived at the American-owned plant.

Finding the source of that contamination will be next to impossible, given the sheer size and breadth of the largely un-regulated industry currently churning out raw heparin, produced mostly in small shops and backrooms as crude and raw as the heparin they produce.

“The supply chain that was used to make the materials is impossible to follow,” said Dr. Bryan Liang, an adviser to the Partnership for Safe Medicines, an American group working to promote drug safety, located in Virginia. “Add to that, Chinese manufacturers are not averse to cutting corners, as we’ve seen in toys, toothpaste, food and drugs.

“This is just the tip of the iceberg in terms of problems with sensitive drugs. The problem is only going to get worse as more materials come from suspect sources.”

It is not clear why the FDA failed to inspect the Changzhou SPL plant prior to giving its approval for the facility to start producing heparin in 2004–a violation of its own policy. However, when an inspection was finally done last month, the Associated Press reported that “unidentified material” was found sticking to the insides of scratched tanks. Records were missing for some of its sources of raw heparin, and testing was incomplete.

A statement made on behalf of Scientific Protein Laboratories, majority owner of the Changzhou SPL facility, suggested “the observations made by the FDA during its inspection do not indicate any fundamental or underlying problems with the Changzhou SPL facility.”

It has been reported that China has no system in place for regulating exports. A pact signed in December between the US and Chinese governments to improve co-operation in drug safety has aided the investigation. However, heparin is said not to be on the list of drugs covered by the agreement. Even with inspections, heparin is tricky, said Liu Jian, an expert on the chemical at the University of North Carolina, in an Associated Press report.

“In producing heparin, it’s very important to control the quality of the raw heparin,” Liu said. “Once you have a contaminant that you didn’t get rid of in the early stages, it’s very hard to tell what you have there.”

While all this is sorted out, patients adversely affected by tainted heparin may have no shortage of hosts to which assess and assign blame: manufacturers for increasingly moving production off-shore in an effort to increase profits and lower costs, regulators without the resources to properly police the supply, and the government itself for not equipping its own regulatory authority, thus allowing this issue to reach such a crisis.

Future crises, notwithstanding.

Covidien announced the voluntary recall March 28th of 32 lots of Heparin Lock Flush Syringes containing various concentrations of heparin. The recall, announced in concert with the US Food and Drug Administration (FDA), comes on the heels of similar recalls by Baxter International, and B. Braun.

The most telling aspect of this latest recall, however, is the identity of Covidien’s supplier–Scientific Protein Laboratories LLC–the same supplier implicated in the two prior recalls.

A Wisconsin-based company, Scientific Protein Laboratories (SPL) operates a facility in China that refines crude heparin obtained from consolidators, who in turn source the material from various suppliers, many of them unregulated.

The initial recall by Baxter came amidst hundreds of reports of adverse reactions to heparin, and the potential for 19 deaths that may have been linked to heparin products. The FDA noted at the time that while standard testing methods turned up nothing sinister in the suspected heparin, advanced testing techniques identified an unknown heparin-like contaminant, which was found to be present in terms of volume, at concentrations of 20 percent to 50 percent of actual heparin, in heparin solution.

Further scrutiny concluded that the mystery mimic was oversulfated chondroitin sulfate. Yet to be determined is why this heparin mimic was put into the mix, and what effect it has on the health of heparin patients.

However, at the time of the massive Baxter recall earlier in the year, industry insiders were confident that even with the size of the Baxter market–Baxter has a huge footprint in the global heparin market–there would be sufficient supply to take up the slack, until the whole mess was sorted out.

Then came the B Braun heparin recall, followed a few weeks later by this latest recall announced in late March. Covidien has indicated they have received no adverse reaction reports with regard to its heparin products, but decided to initiate the voluntary recall as a precaution after it was notified by SPL that “two lots of Heparin Sodium USP Active Pharmaceutical Ingredient acquired by Covidien contained a heparin-like contaminant,” according to information posted on the FDA web site.

No further information was issued by SPL as to the source of the contaminated heparin. However, an SPL-owned plant in China, known as Changzhuo SPL, has been linked to both the Baxter and B. Braun recalls, and SPL has confirmed that the tainted heparin has been found at its China facility. The current investigation centers on the supply chain going to Changzhuo SPL.

While the FDA and various other players grapple with the China connection, including a huge and largely unregulated cottage industry that fashions crude heparin in often crude conditions from the intestines of pigs, the larger question is how many fingers does SPL have in the heparin pie? So far, three of the largest recalls of tainted heparin have been linked to Scientific Protein Laboratories. One has to wonder how many other pharmaceutical companies source their refined heparin from SPL, and if there will be more recalls in the offing?

Beyond that, with China having been granted such a large supply footprint in the heparin world, what would this do to the global supply, if more heparin is found to be tainted, or potentially so?

Stay tuned. For a complete listing a recalled Covidien (formerly known as Tyco Healthcare) heparin pre-filled syringes, visit visit here.

Typical symptoms of adverse reaction to tainted heparin include anaphylactic-like responses such as low blood pressure, shortness of breath, nausea, vomiting, diarrhea and abdominal pain.

An FDA spokesperson assures that “we’re not talking about a large amount” of heparin, in such devices. Still, amidst revelations that as much as 50 percent of the active ingredient of heparin inbound from China has been substituted with a counterfeit ingredient, one has to wonder about the long-term effects to constant exposure.

A week ago the FDA announced that deaths linked to tainted heparin from China have tripled, from 19 to 62 since January of last year. In contrast, there were just three deaths due to allergic reactions to heparin in all of 2006.

In the last several weeks, the media has been awash in recall reports. First it was Baxter International–one of the largest suppliers of heparin in the US–followed by B Braun Medical Inc., then Covidien on March 28th.

German manufacturer RotexMedica GmbH recalled batches of Chinese-produced heparin after reports of 80 allergic reactions. There have been no deaths reported so far in Germany. In March, the European Medicines Agency reported that health authorities in Denmark, France and Italy have also recalled heparin in their respective jurisdictions, as a precaution. Japan, too.

At the center of the heparin crisis is a newly-identified counterfeit ingredient that has found its way into the heparin sourced from China: oversulfated chondroitin sulfate, a derivative of animal or shark cartilage taken as a food supplement by patients experiencing joint pain. In response to the spike in adverse reactions (800 reports so far) and patient deaths linked to the blood thinner, the FDA utilized more sophisticated testing.

That’s when the oversulfated chondroitin sulfate was discovered. Why it was found in heparin is unclear. However, it has been reported that the substance is seven times less expensive than pure heparin, while impersonating heparin so well from a chemical standpoint that it’s hard to spot.

One can imagine the motive, given past indiscretions on the part of Chinese suppliers involving pet food, toothpaste, children’s toys and cough medicine. The latter was responsible for the deaths of 93 people in Central America, many of them children, a year ago.

Heparin, refined from the mucous membranes of pigs, has been around for decades and is used as a blood thinner for various procedures, including dialysis and some surgeries.

It should be noted that heparin used to be made primarily in the US and Europe. However, over the last two decades production has shifted to low-cost, developing countries.

“We have an increasingly globalized supply chain,” said James Shen, publisher of the industry newsletter Pharma China, in an Associated Press news report. “The Chinese are now major suppliers of bulk pharmaceuticals and also supply intermediate chemicals for drugs.

“It is likely we will continue to see the same problems with other drugs,” he added.

So far the facility in China at the center of the crisis, Changzhou SPL near Shanghai, has not been shown to be the actual source for the contaminant. In other words, the oversulfated chondroitin sulfate got into the supply chain before it arrived at the American-owned plant.

Finding the source of that contamination will be next to impossible, given the sheer size and breadth of the largely un-regulated industry currently churning out raw heparin, produced mostly in small shops and backrooms as crude and raw as the heparin they produce.

“The supply chain that was used to make the materials is impossible to follow,” said Dr. Bryan Liang, an adviser to the Partnership for Safe Medicines, an American group working to promote drug safety, located in Virginia. “Add to that, Chinese manufacturers are not averse to cutting corners, as we’ve seen in toys, toothpaste, food and drugs.

“This is just the tip of the iceberg in terms of problems with sensitive drugs. The problem is only going to get worse as more materials come from suspect sources.”

It is not clear why the FDA failed to inspect the Changzhou SPL plant prior to giving its approval for the facility to start producing heparin in 2004–a violation of its own policy. However, when an inspection was finally done last month, the Associated Press reported that “unidentified material” was found sticking to the insides of scratched tanks. Records were missing for some of its sources of raw heparin, and testing was incomplete.

A statement made on behalf of Scientific Protein Laboratories, majority owner of the Changzhou SPL facility, suggested “the observations made by the FDA during its inspection do not indicate any fundamental or underlying problems with the Changzhou SPL facility.”

It has been reported that China has no system in place for regulating exports. A pact signed in December between the US and Chinese governments to improve co-operation in drug safety has aided the investigation. However, heparin is said not to be on the list of drugs covered by the agreement. Even with inspections, heparin is tricky, said Liu Jian, an expert on the chemical at the University of North Carolina, in an Associated Press report.

“In producing heparin, it’s very important to control the quality of the raw heparin,” Liu said. “Once you have a contaminant that you didn’t get rid of in the early stages, it’s very hard to tell what you have there.”

While all this is sorted out, patients adversely affected by tainted heparin may have no shortage of hosts to which assess and assign blame: manufacturers for increasingly moving production off-shore in an effort to increase profits and lower costs, regulators without the resources to properly police the supply, and the government itself for not equipping its own regulatory authority, thus allowing this issue to reach such a crisis.

Future crises, notwithstanding.

In a detailed analysis by the US Food and Drug Administration (FDA), it is reported that most of the deaths were reported over a 3-month window beginning in December of last year, followed by deaths in January and February of this year. There have been no reports of deaths since the end of February, when Baxter initiated the recall. Covidien, which was formerly known as Tyco Healthcare, and B. Braun recalled much of its heparin product as well, as a precaution.

All three companies recalled product with ties to China, and the same plant used to refine and process crude heparin sourced from the vast, and largely unregulated heparin harvesters in the country.

Scientific Protein Laboratories (SPL), a Wisconsin-based enterprise with majority ownership of Changzhuo SPL in China, has been identified as a common denominator in all recalls involving the three heparin manufacturers. SPL has confirmed that its plant served as an unknowing thruway for contaminated heparin–however what is not conclusively known is just where the crude heparin came from. SPL has said in the past that it purchased its crude heparin, fashioned from mucous membrane extracted from the intestines of pigs, from trusted consolidators who could vouch for their own suppliers.

However, there have been reports that mom-and-pop heparin huts, which number into the thousands and constitute a huge, and unregulated cottage industry in China, have sold their wares directly to the consolidators. One heparin worker, toiling in deplorable conditions, told a New York newspaper several weeks ago that she had, on at least one occasion, sold crude heparin directly to Changzhuo SPL.

According to the FDA, which has done its first intensity on the heparin deaths, there were just 3 suspicious deaths reported in 2006. However, heparin reactions began, and the death rate increased over a 14-month period beginning in January of last year. The agency defines suspicious deaths as those involving one or more allergic reactions, or a drop in blood pressure.

What proved confusing was that standard testing revealed no problem with the heparin whatsoever. It wasn’t until the FDA implemented a more sophisticated test that the contaminant showed up.

That contaminant was revealed as oversulfated chondroitin sulfate (OCS), a substance derived from fish that is commonly used to treat arthritis, and while similar to actual heparin, OCS is not the real McCoy. There is, thus far, no data to determine just how the counterfeit ingredient reacts in the human body when mixed with real heparin.

That mix, by the way, has ranged from 20 per cent, to as high as 50 per cent of volume. It has also been determined that OCS is much cheaper to produce than real heparin. While it has not been determined just why the counterfeit OCS was used to bolster the volume of the genuine heparin, various theories remain. An outbreak of blue ear pig disease last year throughout many provinces of China severely depleted stock, and drove prices up. As well, the contamination with a counterfeit ingredient smacks of past misdeeds, which include mixing toxic melamine into pet food to mimic protein levels, diethylene glycol (anti-freeze) into toothpaste to mimic the more expensive consumer-grade glycerin, and less-expensive lead paint used in children’s toys.

Heparin is a drug thinner commonly used in dialysis and other types of surgery. Similar heparin recalls have taken place in Germany, Denmark, France, Italy and Japan. The Chinese drug authorities have vowed to crack down on the heparin industry in China–but that will be easier said than done, as thousands of family-run heparin huts scattered across the provinces make the stuff.

Meantime the FDA has long been criticized for not having the resources to police an ever-expanding import trade of drug manufacturing, supplies and raw materials coming in from foreign shores, particularly China. It was recently reported that it would take decades for the FDA to inspect all foreign drug-manufacturing plants. As it was, it allowed Changzhuo SPL to go ahead with heparin production in 2004 without an inspection by the agency, which is in direct violation of its protocol and policy.

Covidien announced the voluntary recall March 28th of 32 lots of Heparin Lock Flush Syringes containing various concentrations of heparin. The recall, announced in concert with the US Food and Drug Administration (FDA), comes on the heels of similar recalls by Baxter International, and B. Braun.

The most telling aspect of this latest recall, however, is the identity of Covidien’s supplier–Scientific Protein Laboratories LLC–the same supplier implicated in the two prior recalls.

A Wisconsin-based company, Scientific Protein Laboratories (SPL) operates a facility in China that refines crude heparin obtained from consolidators, who in turn source the material from various suppliers, many of them unregulated.

The initial recall by Baxter came amidst hundreds of reports of adverse reactions to heparin, and the potential for 19 deaths that may have been linked to heparin products. The FDA noted at the time that while standard testing methods turned up nothing sinister in the suspected heparin, advanced testing techniques identified an unknown heparin-like contaminant, which was found to be present in terms of volume, at concentrations of 20 percent to 50 percent of actual heparin, in heparin solution.

Further scrutiny concluded that the mystery mimic was oversulfated chondroitin sulfate. Yet to be determined is why this heparin mimic was put into the mix, and what effect it has on the health of heparin patients.

However, at the time of the massive Baxter recall earlier in the year, industry insiders were confident that even with the size of the Baxter market–Baxter has a huge footprint in the global heparin market–there would be sufficient supply to take up the slack, until the whole mess was sorted out.

Then came the B Braun heparin recall, followed a few weeks later by this latest recall announced in late March. Covidien has indicated they have received no adverse reaction reports with regard to its heparin products, but decided to initiate the voluntary recall as a precaution after it was notified by SPL that “two lots of Heparin Sodium USP Active Pharmaceutical Ingredient acquired by Covidien contained a heparin-like contaminant,” according to information posted on the FDA web site.

No further information was issued by SPL as to the source of the contaminated heparin. However, an SPL-owned plant in China, known as Changzhuo SPL, has been linked to both the Baxter and B. Braun recalls, and SPL has confirmed that the tainted heparin has been found at its China facility. The current investigation centers on the supply chain going to Changzhuo SPL.

While the FDA and various other players grapple with the China connection, including a huge and largely unregulated cottage industry that fashions crude heparin in often crude conditions from the intestines of pigs, the larger question is how many fingers does SPL have in the heparin pie? So far, three of the largest recalls of tainted heparin have been linked to Scientific Protein Laboratories. One has to wonder how many other pharmaceutical companies source their refined heparin from SPL, and if there will be more recalls in the offing?

Beyond that, with China having been granted such a large supply footprint in the heparin world, what would this do to the global supply, if more heparin is found to be tainted, or potentially so?

Stay tuned. For a complete listing a recalled Covidien (formerly known as Tyco Healthcare) heparin pre-filled syringes, visit visit here.

Typical symptoms of adverse reaction to tainted heparin include anaphylactic-like responses such as low blood pressure, shortness of breath, nausea, vomiting, diarrhea and abdominal pain.

What also needs to be answered is why the counterfeit was used in the first place. Why, and how?

“The greatest question of all, however, is what to do about the reality that the majority of the world’s heparin supply comes from China–a country that has already been found to be suspect in several instances regarding tainted drugs and consumer goods.

And how is this situation to be rectified if the US Food and Drug Administration (FDA) continues to be under funded, and denied the resources and reformation needed to adequately respond to the perpetual increase of prescription drugs, and raw materials coming into the country from distant shores?

As it was, the mystery substance–over-sulfated chondroitin sulfate–escaped detection when normal testing methods were used. It wasn’t until the FDA undertook more sophisticated testing methods that the counterfeit ingredient was even noticed at all, let alone identified.

That would also explain why random tests of heparin coming in from China have not been singled out in the past.

Over-sulfated chondroitin sulfate has been described as a modified version of a substance derived from shark, squid and other fish and used normally for the treatment of joint pain.

The latter in its normal form–chondroitin sulfate–has been identified as being structurally similar to heparin and shares some of the blood-thinning properties that heparin presents. However, it is definitely not heparin, and neither is the modified version known as over-sulfated chondroitin sulfate. The latter is not approved for any purpose in the United States, and certainly should not be found in heparin, regardless of its capability to mimic the real thing, for any reason.

Previous reports had suggested that lots of tainted heparin tested with as much as 20 per cent of the heparin volume represented by the over-sulfated chondroitin sulfate mimic.

However, more recent reports increase the ratio to 50 per cent, in some cases. With only half of a heparin injection the real thing and the other half a potential heparin mimic structurally similar to heparin but not spot-on, the threat to a human with such a mixture coursing through the veins is palpable. The body’s response to this modified chondroitin sulfate, and how it interacts when mixed with heparin in the human body, remains a huge unanswered question.

Over the last several weeks two major companies have recalled virtually their entire heparin product sourced back to an American-controlled factory in China, Changzhuo SPL, which has been linked to the tainted heparin. Now comes the task of definitively determining the supply chain to the factory. China is home to a huge cottage industry of raw heparin houses, which prepare crude heparin from the intestines of pigs.

Much of the heparin industry in China is not regulated. Others escape regulation with registration as a chemical entity, rather than a manufacturer of drugs.

For now, it appears as if the Chinese authorities are co-operating with US officials in an effort to determine the source, and the reason for the contamination. Owners of other regulated factories in China are reporting impromptu visits from Chinese health authorities as the latter attempts to verify the safety and efficacy of the status quo.

However, the same cannot be said for the unregulated sources, which reports suggest number into the thousands. How China manages to address that situation, if it’s even possible, is the subject for much debate.

In a perfect world, whatever is determined to be the cause of the heparin contamination would be dealt with, and anything and anyone falling through the regulatory cracks would be fixed. Together with ongoing scrutiny on the part of both Chinese and American officials, no less a response will be required to assure that the majority of the global supply of crude heparin, assuming it continues to originate from China, is deemed safe.

However, any American injured by tainted heparin, or any American having lost a loved one to contaminated heparin from China, will be hard pressed to find one entity to blame.

There are so many…

While one cannot fault the drug companies–any company, for that matter–for wanting to cut costs in any legitimate fashion, one would hope that any manufacturer importing either raw, or refined materials would carry out routine testing, as should the FDA.

Beyond that, however, is the reality that medicinal exports from China and other offshore ports have snowballed, but the FDA can’t appear to, or hasn’t been given the resources from Congress, to keep up. As it is, the Changzhuo SPL plant in China was never inspected by the FDA prior to beginning heparin operations in 2004, a contravention of the FDA’s own policy.

Who to blame, therefore? The FDA? Congress? The pharmaceutical companies? China?

All of them.

When it comes time to sue, it’s a case of eenie, meenie, mynee, moe…