Two years ago this month Baxter first recognized it had been selling contaminated heparin. We now know that this contamination was intentional, sophisticated, and deadly. Heparin is a sugar molecule, one of several glycosaminoglycans (GAGs) found naturally in the lining of the intestine of pigs. The contaminant also was a GAG. In fact, the contaminant may have been a combination of GAGs, all of which are found in crude heparin, the starting material for heparin.

Crude heparin consists of 4 GAGs, namely Dermatan Sulfate (DS), Chondroitin Sulfate (CS), Heparan Sulfate (HS) and Heparin. Responsible manufacturers have known of the requirement to test for the DS and CS to make sure their heparin is pure. If Baxter or its supplier, SPL, had been performing simple tests which were then in existence, they would have known and realized that their heparin was full of impurities.

These impurities, the contaminants, were easily distinguishable from heparin; yet Baxter failed to perform any testing to insure its heparin was free of common GAG impurities.

The contaminants included Chondroitin Sulfate which had been "sulfated", or chemically modified, to make it have anti coagulation properties. Heparin is an anticoagulant. So one of the purposes of adding the contaminant was to increase the anticoagulation properties.

The recipe for the contamination had been published by Robert Lindhardt in 1997 in a scientific journal, along with claims that this oversulfated chondroitin sulfated product had value as a heparin like compound:

It is possible that the anticoagulant activity can be
further increased by appropriate refinement of the
modification procedure for N-deacetylation–N-desulfonation
w26x of fully O-sulfonated chondroitin
sulfate. These possibilities point to new practically
feasible routes for the generation of heparin-like
compounds with various pharmacologically relevant
biological activities.

http://www-heparin.rpi.edu/

Unfortunately Baxter was too busy counting the profits from its cheap Chinese heparin to pay attention to what it was selling. Some one with a college education who was able to read scientific literature figured out that a cheap substitute for heparin could be made from the by product produced during the manufacture of heparin. All that had to be done was to follow the recipe published in 1997.

There are basically 2 classes of GAGs found in crude heparin. Heparin itself contains glucosamine. The contaminants included heparin byproducts that contain galactosamine. DS and CS both are galactosamines. Therefore the simple tests that had been used for decades to make sure the heparin had been properly purified to remove all of the galactosamine-containing GAGs would have also detected the contamination.

Recently published studies indicate that the contaminant was made from byproduct generated during the manufacture of heparin itself. http://ash.confex.com/ash/2009/webprogram/Paper17902.html

Neither the FDA nor the USP wants to admit that the contamination was a result of their inability to perform basic inspections and to require basic purity tests. However the failures of these organizations does not relieve Baxter or its supplier from responsibility.

The identity of the individuals and organizations responsible for intentionally contaminating Baxter's heparin remain a secret. But the list of suspects is actually pretty short. The FDA has still not finalized its investigation. Either the FDA has abandoned the hunt or they are closing in on the responsible party.

Meanwhile our civil justice system continues to grind ahead. Sooner or later Baxter and SPL will be held accountable. There are currently about 750 claims for death or permanent injury pending in federal and state courts. Hundreds more died without their survivors realizing they were victims of corporate greed.

The final chapter has yet to be written.

Labels: Baxter Heparin, Heparin, Heparin Class Action, heparin disaster, SPL

Labels: Baxter, Baxter Heparin, contaminated heparin, contamination, Heparin, heparin attorney, Heparin Class Action, heparin disaster, heparin lawyer; heparin safety, OSCS, Scientific Protein Labs, SPL

Labels: Baxter, Baxter Heparin, Chinese heparin, FDA, Heparin, heparin attorney, Heparin Class Action, heparin disaster, heparin lawsuit, heparin lawyer, Scientific Protein, SPL

The Washington Post reported today that former officials, members of Congress, watchdog groups and various government reports are calling for an overhaul of the FDA, which “desperately needs an infusion of strong leadership, money, technology and personnel -- and perhaps a major restructuring.” (11/26/08 Washington Post, “Ailing FDA May Need a Major Overhaul, Officials and Groups Say.”)

The article is worth the read and discusses some of the FDA’s recent failures to monitor imported drugs and consumer products, including contaminated heparin, toothpaste, and pet food from China. As similarly opined in this blog recently, the article also discusses the view that more needs to be done than simply starting to open offices overseas, including sharply boosting inspections abroad, developing strict new regulatory standards, and updating and integrating the FDA's computer systems. To read a copy of this article, click here.

Labels: Baxter, Baxter Heparin, China, Chinese, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, SPL

Labels: Baxter, Baxter Heparin, China, Chinese, contamination, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, Hubley, nightline, OSCS, SPL

On October 23, 2008, The Institute for Safe Medication Practice, (a nonprofit group that educates the healthcare community about safe medication practices), issued a report on the number of serious injuries and death reported to the U.S. Food and Drug Administration in the first quarter of 2008. (See Inst. For Safe Med. Practices: 10/23/08, “Quarter Watch: 2008 Q 1.”)

According to this report, the number of reports of serious injuries and death linked to medications hit a record high. In the first three months of 2008, there were 20,745 new cases of serious injury and 4,824 reports of death. This total was 38% higher than the average for the previous four quarters, and the highest for any quarter. Death cases also accounted for a larger share with 23% for the first quarter of 2008 as compared to a historical average of 16%. This represented a 2.6 fold increase from the previous quarter and the highest number of deaths in a calendar quarter since 2004.

Two drugs accounted for a disproportionate share, including Chantix, a new anti-smoking drug from Pfizer, Inc. (with 1001 cases of serious injury and 50 deaths), and Heparin imported from China, (with 779 cases of serious injury and 102 deaths). (The FDA has actually reported receiving 238 reports of death from contaminated heparin over a longer period, but 102 represent the first quarter.)

Even scarier for the American public is the fact that because reporting is voluntary, these reports represent “only a small fraction of the adverse drug events that occur.” Id. at 1.

As concluded by the Institute, “While prescription drugs bring great benefits to millions of patients and most are used safely, these data show the need for additional progress to better manage the risks to patients….It also underlines the importance of the nation’s system for assuring drug product stability and purity. The scale of injury--hundreds of deaths or serious injuries in a short period—underlines the importance of strengthening oversight of drug manufacture abroad.” Id. at 4.

Labels: Baxter, Baxter Heparin, Chantix, China, contamination, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, Institute for Safe Medication Practice, SPL

A recent editorial, “No Haven for Dangerous Drugs,” published in the Boston Globe emphasizes the importance of a case often discussed in this blog, Wyeth v. Levine (06-1249), which deals with federal preemption of state drug labeling law and is set to be argued before the U.S. Supreme Court on November 3, 2008.

The Boston Globe Editorial highlights the importance of the issue of preemption in our present times. Given the increasing number of dangerous and defective pharmaceutical drugs and medical devices, such as tainted heparin, and the significant number of Congressional Hearings exposing the shortcomings and clear limitations of the U.S. FDA, barring any claim simply because it received FDA approval is a mistake. Indeed, as noted in the editorial, the U.S. FDA itself is among the many groups who support the argument that federal preemption should not bar a victim’s right to redress.

This editorial is worth reading and is available by clicking here.

Labels: Baxter, Baxter Heparin, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, Levine, MDL, preemption, SPL, Wyeth

On Monday, Chinese health officials raised the total number of infants sickened by Sanlu brand milk powder to more than 1,200. (09/15/08 USA TODAY, “Tainted Milk Sickens More than 1,200 Babies in China.”)

The formula was spiked with the industrial chemical, melamine, a contaminate that causes kidney stones (which are otherwise rare in infants). (Id. See also 9/12/08 FDA PRESS RELEASE, “FDA Issues Health Information Advisory on Infant Formula.”) Like the Heparin scandal, the contamination was intentional and a result of corporate greed. Specifically, Chinese investigators say melamine was added to make the milk seem higher in protein and thus, fool quality tests after water was added to fraudulently increase the milk's volume. (Id.)

Unlike the Heparin tragedy, however, it appears that Americans might have missed this latest batch of contaminated products manufactured in China. The FDA has indicated “that there is no known threat of contamination” as “no Chinese manufacturers of infant formula have fulfilled the requirements to sell infant formula in the United States.” (9/12/08 FDA PRESS RELEASE, “FDA Issues Health Information Advisory on Infant Formula.”) Yet, the FDA has not completed its current investigation as to whether or not infant formula manufactured in China is being sold in specialty markets which serve the Asian community. (Id.)

Regardless, this latest contamination is another example of why drugs and other products manufactured in poorly regulated foreign countries cannot be blindly accepted as pure. It should continue to serve as a warning to large U.S. companies who buy these cheaper products and pass them on to the unsuspecting American public…A warning, which unfortunately, was ignored by the big drug company, Baxter, in the heparin disaster that killed numerous Americans.

Labels: Baxter, Baxter Heparin, China, Chinese, contamination, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, import safety, OSCS, oversulfated chondroitin sulfate, SPL

Recently, the New England Journal of Medicine (NEJM) voiced strong opposition to preemption of cases involving defective medical devices and drugs, which would strip Americans injured by defective medical devices or drugs of their constitutional right to a trial by jury for most, if not all, legal claims, where the drugs or medical devices are regulated or approved by the FDA.

In an Amicus Brief filed in a case pending before the United States Supreme Court, Wyeth v. Levine, the NEJM editors wrote that the “FDA alone simply lacks the ability to serve as the sole guarantor of drug safety'’ and that without the discoveries made by plaintiff’s lawyers as a result of defective drug lawsuits, “the FDA would be stripped of an essential source of information that the agency has consistently relied on when making its regulatory decisions, and the American public would be deprived of a vital deterrent against pharmaceutical company misconduct.'’

A copy of this compelling brief is available by clicking here. In addition, the recent NEJM article, “Why Doctors Should Worry about Preemption,” is available on the NEJM’s website, by clicking here.

Labels: Baxter, Baxter Heparin, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, OSCS, preemption, SPL

Last week, the Los Angeles Daily Journal reported that the California Pharmacy Board will be citing and fining 94 California hospitals and the head pharmacist at each facility for not removing (and in some cases actually dispensing) contaminated heparin from their hospital pharmacies. (George, Los Angeles Daily Journal, 8/20)

This failure is inexcusable, as these institutions have been warned in writing on numerous occasions, including, for example, the FDA’s April 25, 2008 “Update to Healthcare Facilities and Healthcare Professionals about Heparin and Heparin-Containing Medical Products.”

Patients receiving heparin therefore, should remain cognizant of the recall and demand assurances from their health-care providers that they have complied with the recall.

Labels: Baxter Heparin, california hospitals, FDA, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, SPL

Last night, our client, Leroy Hubley, and his family, were featured on ABC’s television news program, “Nightline,” which discussed the heparin disaster. (07/30/08 Nightline, “Pharmaceutical Companies Must Take Responsibility.”)

The Hubley family, like hundreds of others, lost loved ones as a result of the contaminated heparin sold by Baxter, and supplied by SPL. The Hubley family not only lost their mother, Bonnie Hubley, but their 47 year-old son, Randy Hubley.

Previously on April 29, 2008, the Hubley family, along with Johanna Staples, (another client of Zoll, Kranz & Borgess who lost her husband, Dennis Staples), were invited to tell their tragic stories to the U.S. House Commerce Committee on Energy and Commerce at a hearing entitled, “The Heparin Disaster: Chinese Counterfeits and American Failures.” Video of this hearing is available by clicking on the links below.

Panel I (Witnesses: David Nelson, Senior Investigator for the Committee on Energy and Commerce, Colleen Hubley, Leroy Hubley, and Johanna Marie Staples)

Panel II (Witnesses: Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research, Deborah M. Autor, Director of FDA’s Office of Compliance, and Regina T. Brown, Consumer Safter Officer of the FDA’s Division of Field Investigations)

Panels III and IV (Witnesses: Robert Parkinson, CEO and President of Baxter International, Inc., David Strunce, CEO of Scientific Protein Laboratories, Yan Wang, Ph.D., Vice President of Business Development and Research at Scientific Protein Laboratories, and Clive Meanwell, CEO of The Medicines Co.)

In addition, the written statements submitted to Congress by Leroy Hubley, Colleen Hubley Johanna Staples, and other witnesses, are available by clicking on their name below:

• Leroy Hubley
• Colleen Hubley
• Johanna Staples
• David Nelson, Senior Investigator for the Committee on Energy and Commerce
• Janet Woodcock, Director of the FDA’s Center for Drug Evaluation
• Robert Parkinson, CEO and President of Baxter International, Inc.
• David Strunce, CEO of Scientific Protein Laboratories
• Clive Meanwell, CEO of The Medicines Co.

We are proud and honored to represent these brave individuals, who have selflessly agreed to share their private losses and suffering with the public so that the extent and severity of this tragedy may be exposed and hopefully, prevented in the future.

Labels: Baxter, Baxter Heparin, FDA, heparin attorney, heparin lawsuit, heparin lawyer, Hubley, Johanna Staples, Leroy Hubley, nightline, OSCS, over sulfated chondroitin sulfate, Randy Hubley, SPL

Today the Chicago Tribune reported that the FDA has only been able so far to "conclusively link" three fatalities to contaminated heparin manufactured by Baxter. (07/30/08 Chicago Tribune: Heparin Taint Tied to Deaths.)

According to the article, in an interview Tuesday with the Tribune, the FDA said it completed its review of 93 death reports related to heparin that the agency received from January 1 to March 31, 2008. (07/30/08 Chicago Tribune: Heparin Taint Tied to Deaths.) Of the 10 reports of death from severe shock known as anaphylaxis or hypotension, three of those could be traced to lot numbers of Baxter products that tested positive for oversulfated chondroitin sulfate (“OSCS”). Heparin lot numbers were not known for the other seven deaths from anaphylaxis or hypotension, so the FDA could not determine whether those 7 patients received heparin contaminated with the substance.

Of the remaining 83 reports, 13 were described as "potential complications of heparin use" such as bleeding; and 25 cases were due to causes unrelated to heparin use such as pneumonia, sepsis and kidney failure. (07/30/08 Chicago Tribune: Heparin Taint Tied to Deaths.) In the remaining 45 deaths, FDA spokeswoman Janet Woodcock stated, "clinical information in the adverse-event reports is insufficient to specify the cause of death with clinical certainty,” and that the FDA was missing information from providers or others who filled out the reports to make an adequate determination. She also added, "While some of these [reports] appear definitely related [to contaminated heparin] many are still in the gray zone…We have looked over all of these death reports and a number of them were probably not related to the contaminated heparin."

While it is good that the FDA has finally conclusively linked some of the deaths, many questions are still unanswered. The top five questions that immediately jump out to me are as follows:

1) If additional information is needed to determine whether additional deaths are related, why isn’t this information being gathered or at least requested from the providers or others who filled out the reports to make an adequate determination? For example, we have filed multiple adverse-event reports of clients, but to date WE HAVE NEVER BEEN CONTACTED BY THE FDA REGARDING THESE REPORTS, NEVER BEEN ADVISED OF THE STATUS OF THEIR INVESTIGATION, OR TOLD THAT ADDITIONAL INFORMATION IS NEEDED.

2) Is the FDA relying on death certificates to determine cause of death? If so, this analysis is suspect, as many individuals died before the public recall and before the medical community learned of the contaminated heparin. As such, a medical provider would not have known or appreciated that their patient could have died from an anaphylactic reaction from contaminated heparin.

3) Is the FDA investigating or supporting scientific studies to determine whether the contaminate, OSCS, and its resulting symptoms can cause or contribute to other complications leading to death, such as heart failure? To date, the FDA admits that it has limited knowledge “since the contaminant was only recently discovered.” (See FDA Questions and Answers, updated 7/3/08.) For example, the FDA admittedly does not know whether there are any long term health effects of the contaminant. (See FDA Questions and Answers, updated 7/3/08.) With the New England Journal of Medicine article (that had severely restricted testing parameters) being the only scientific study published to date regarding the effects of OSCS, it may be too quick to report that the only deaths caused by that contaminate are those from anaphylaxis or hypotension.

4) Why has the FDA failed to analyze any of the reports that were filed after March 31, 2008? Or if they have analyzed them, why have they failed to report on them?

5) Why did it take an interview with the Chicago Tribune to ferret out this important information?

Baxter, SPL and the FDA have each admittedly failed the American public with respect to Heparin. As such, it is in their best interests to minimize the national disaster that they allowed to occur. It is no wonder, therefore, that they are quick to try to limit the number of deaths. Speculation is worthless. What we need is science. We implore the scientific community to not accept the FDA’s and drug companies’ unfounded conjectures at face value, but to test and study this contaminate further. Only then will we reach the truth… something that the victims of this disaster and their loved ones deserve.

Labels: Baxter, Baxter Heparin, China, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, nightline, OSCS, oversulfated chondroitin sulfate, Scientific Protein Labs, SPL

According to Chinese news, the Chinese Ministry of Health announced Friday that despite its “joint investigation” with U.S. drug authorities, it could still not conclude that the multiple U.S. deaths were a result of contaminated heparin sold by Baxter, who bought the raw ingredient supplied by SPL from its facility in China, SPL Changzhou. (07/18/08 China View News: “Cause of deaths still in doubt after Sino-U.S. Investigation on Blood Thinner.”)

As you may recall, China’s drug agency reported the same inability to link the reported deaths in May of this year. (See our May 7, 2008 Blog: China Points the Finger at Baxter and the FDA.”) At that time, the inability of China and the U.S. FDA to cooperate was evident. Chinese officials claimed that Baxter and the FDA failed to provide them with medical records, medical histories, and information on Baxter's manufacturing practices. The Chinese also complained that they had not been given samples of the contaminated product. The FDA complained that it was not provided records from Changzhou Techpool Pharmaceutical Co. (“CZTP”), a company who supplied SPL Changzhou with raw heparin and may have been a source for the contaminant.

U.S. researchers confirmed the link between the adverse events, including death, and the contaminant, OSCS, since at least April 23, 2008, when the results of the first study were reported in an article published online by the New England Journal of Medicine entitled, “Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System.” As reported on the FDA website, “The contaminant activates chemicals in the body called enzymes. These enzymes cause the body to make inflammatory mediators (chemicals that are released by immune cells). Inflammatory mediators can lead to some of the symptoms such as low blood pressure, abdominal symptoms and shortness of breath.” (FDA: Questions and Answers re Heparin.)

It seems, therefore, that the two agencies are still failing to cooperate and exchange pertinent information. Maybe someone should give the Chinese Ministry of Health a copy of the New England Journal of Medicine article.

Labels: Baxter, Baxter Heparin, Changzhou, China, Chinese, FDA, Heparin, heparin lawsuit, heparin lawyer, MDL, nightline, OSCS, over sulfated chondroitin sulfate, oversulfated chondroitin sulfate, SPL

Last week, the U.S. Department of Health and Human Services (HHS) announced a new program in conjunction with the U.S. Food and Drug Administration (“FDA”) to enhance the safety of medical drugs and food exported to the United States. (07/09/08 HHS Press Release.)

Specifically, the program is a pilot project with the European Union and Australian authorities “to jointly plan, allocate for and conduct inspections of drug-manufacturing facilities.” (07/09/08 HHS Press Release.) The program will initially focus on makers of active pharmaceutical ingredients, but will expand to other types of manufacturing facilities if successful.

Additional information about this import safety initiative, as well as other import safety news, reports and blogs are available at the HHS’ import safety website: http://www.importsafety.gov/.

Labels: Baxter, Health and Human Services; HHS; FDA; European Union;, Heparin, heparin lawsuit, heparin lawyer, heparin medical device, import safety, nightline, OSCS, over sulfated chondroitin sulfate, SPL

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Labels: Baxter, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, MDL; Multi-District Litigation, Monograph, National Formulary, nightline, OSCS, oversulfated chondroitin sulfate, Pharmacopeia, SPL, USP

The information in this post is based on information in the public domain.

We have written earlier about Scientific Protein Labs (SPL) and the role they played in providing Baxter with the heparin that had been cut with oversulfated chondroitin sulfate. But unlike Baxter, which is a publicly traded company, the stock in SPL is privately held. 89% of SPL was purchased about 2 years ago for the price of $135 million. The purchaser was American Capital Strategies, Ltd., ("ACAS") a private equity firm headquartered in Bethesda, Maryland, which is publicly traded under the symbol ACAS.

Area biotech sold again: Helps make heparin

The Capital Times

By Mike Ivey
August 23, 2006

A company founded 30 years ago to make use of pig intestines from the Oscar Mayer slaughterhouse has changed owners again.

Scientific Protein Laboratories of Waunakee has been acquired by American Capital Strategies, a Washington, D.C.-area buyout firm that is publicly traded on the Nasdaq stock exchange.

A sales price was not released but the company had sold for $81 million in 2004 to Arsenal Capital Partners, a New York-based private equity firm. Prior to that, the company was a wholly-owned subsidiary of Wyeth Pharmaceuticals.

SPL has 150 employees at its facility here, where it produces the active ingredient used in the manufacture of heparin, a common anti-blood clotting drug. The company also has a small facility in Changzhou, China, with about 30 employees.

Complete Article

ACAS had placed a fair value of $176M on SPL as of 12/31/2007. The total asset value of ACAS is about $11 Billion. Thus SPL represents about 1.6% of ACAS total assets. According to the New York Times story published earlier this week:

American Capital, which owns stakes in some 170 companies, booked $29.6 million in unrealized depreciation related to its investment in Scientific Protein in the first quarter [of 2008].

American Capital’s stock is down about $4 since February, but that appears more related to the company’s write-downs on some of its assets, including mortgage bonds. Jefferies, the investment bank, downgraded American Capital’s stock to underperform in April, but did not mention the tainted blood thinner in its report.

NYT Story May 23, 2008

An article today posted on The Street.com titled "Valuations Haunt American Capital" contains this information:

American Capital's investment in Scientific Protein Labs (referred to as SPL Acquisition in regulatory filings) had a fair value of $176 million on American Capital's balance sheet at the end of 2007. The valuation dropped to $141 million at the end of the first quarter, as American Capital wrote down the value of its preferred-stock investment from $41 million to $10 million. (The news story on the bad heparin broke in the first quarter).

But the firm's $131 million debt investment in SPL was essentially left untouched.

At American Capital's annual investor day last week, one audience member questioned the valuation of Scientific Protein.

"I'm trying to understand, as we're trying to get comfortable with valuations through the portfolio, how the debt of a company that is looking at lawsuits that could probably bankrupt it if even a fraction of them come to fruition, how that can possibly be marked at par?" the unidentified audience member asked a panel of American Capital officials, according to a webcast replay of the event.

American Capital CEO Malon Wilkus, who was in the audience and not on the panel, immediately grabbed the microphone from the questioner, according to an investor who attended the event.

Wilkus said the situation was very sad, but he called Scientific Protein a "very good company ... and we think it will do extremely well," according to the webcast.

He did point out that Scientific Protein had some insurance to cover itself from lawsuits but stopped short of saying how much.

"I think that is about all we can say about the company specifically," he said.

The ACAS public financials do not disclose what amount of money SPL made from the CZ-SPL and China imports. SPL continues to make heparin from domestic sources as well as some other products. But the FDA has blocked any imports of heparin from SPL's wholly owned subsidiary CZ-SPL.

Labels: ACAS, American Capital Strategis, Heparin, heparin attorney, heparin lawyer, LTD, nightline, Scientific Protein Labs, SPL

Labels: Baxter, China, dialysis, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, MDL, nightline, OSCS, oversulfated chondroitin sulfate, SPL

The US FDA inspected, or rather attempted to inspect, three heparin manufacturing facilities between February 20th and February 29, 2008. The first facility was that of Changzhous SPL Company, Ltd., ("CZ-SPL") a wholly owned subsidiary of SPL. All of the CZ-SPL product was shipped to Baxter.

This inspection lasted 6 days. This was the first time the FDA had ever inspected the facility, in violation of FDA policy.

The inspection found that the process validation for the purification of Heparin Crude was inadequate . It further found a number of other deficiences, including:

• process changes included removal of Heparin Crude quality attributes based on ease of procurement without adequate raw material evaluation.
• No impurity profile had been established.
• A discontinued workshop's crude heparin was included in lots sold to SPL.
• Equipment was not cleaned.

The report states that, beginning in June of 2007, CZ-SPL started testing incoming lots by Polymerase Chain Reaction (PCR) for species verification. In other words, because SPL was worried about counterfeit sheep product being substituted for pig product, it started doing a basic PCR analysis. As a result of the inspection, the FDA issued a Form 483 report.

The second inspection began February 27, 2008. This inspection was of a facility located right next door to CZ-SPL. The neighboring factory is known as Changzhou Techpool Pharmaceutical Co. Ltd. ("CT"). CT is 45% owned by CZ-SPL. All of the product made by CT is sold to CZ - SPL. Importantly, the plant is not registered with the Chinese FDA because it does not make product for consumption in China. Nor is it registered with or inspected by the US FDA. The inspection lasted only 2 days. On both days the company refused to give the FDA copies of basic documents, including raw material crude specification, test methods, cards, certificates of analysis, blend records, and inventory records. The FDA did take photographs, which we are seeking to obtain.

The third inspection was even less successful. This inspection began the afternoon of February 28th and ended the next day when the FDA inspection team was refused reentry into the facility. This facility was located in Hangzhou, China. The name of the firm was Hangzhou Ruihua Biochemical Products Co. Ltd. This firm was a manufacturer and tester of crude heparin that was sold to CZ-SPL for further processing. A photograph of Dr. Wang, the general manager of CZ-SPL and an officer of SPL hung in the entryway of the facility.

The firm refused to provide copies of any records and no samples were collected. The firm is not regulated or inspected by the Chinese FDA or the US FDA. The owner of the firm, Mr. Ruihua, admitted that the firm had been unable to meet the needs of CZ-SPL because there was not enough heparin available. He indicated that CZ-SPL was his sole customer.

Ruiha collects raw heparin from the countryside and nearby provinces. The workshops are all on a list provided by CZ-SPL. However Mr. Ruiha refused to provide any documents, refused to permit the FDA to inspect the laboratory, refused to provide a list of the workshops from which they get the raw heparin, and would not even state the Provinces in which the workshops were located.

On April 21, 2008 the FDA issued a warning letter, which held that the deficiencies and deviations from current good manufacturing processes were so severe that CZ-SPL was barred from shipping product into the United States.

Labels: Baxter, Changzhou, China, Chinese, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, MDL; Multi-District Litigation, nightline, OSCS, Scientific Protein, Scientific Protein Labs, SPL

The FDA has updated its website FDA Questions and Answers on Heparin

The latest version contains new questions and answers about Heparin and its uses, further details on the FDA investigation, and describes the contaminant, oversulfated chondroitin sulfate (OSCS) and its effect on the human body.

For example, the new article adds the following question and answer:

18. Why does the contaminant cause serious adverse events? (new question and answer added 6/18/2008)

The contaminant activates chemicals in the body called enzymes. These enzymes cause the body to make inflammatory mediators (chemicals that are released by immune cells). Inflammatory mediators can lead to some of the symptoms such as low blood pressure, abdominal symptoms and shortness of breath. This mechanism can explain many of the serious adverse events that occurred immediately after patients were given the contaminated heparin.

Tomorrow I will write about the FDA inspections of the Chinese facilities.

Labels: Baxter, Changzhou, Chinese, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, nightline, NMR, OSCS, over sulfated chondroitin sulfate, oversulfated chondroitin sulfate, Scientific Protein Labs, SPL

On February 20, 2008, the United States Supreme Court severely curbed the rights of injured victims in the case of Riegel v. Medtronic, which held that the Federal Food, Drug and Cosmetic Act (FDCA) preempts state-law claims seeking damages for injuries caused by medical devices with premarket approval from the FDA. (The problems with preemption have been discussed previously on this blog including, “The Preemption Problem” and “Should FDA Drug and Medical Device Regulation Bar State Liability Claims?”)

However, as reported in the 6/10/08 FDA news Device Daily Bulletin, prominent lawmakers are now seeking to introduce a bill in the next few weeks that would render this harsh U.S. Supreme Court decision moot. (FDAnews Device Daily Bulletin, Vol 5 No. 113, “Device Preemption Ruling Threatened by Draft Bill.”) This important bill would add a subsection to the FDCA stating, “Nothing in this section shall be construed to modify or otherwise affect any action for damages or the liability of any person under the law of any State.” The draft bill is sponsored by Congressmen Pallone and Waxman and is available at: www.fdanews.com/ext/files/FinalBill.pdf.

As this legislation is critical to ensuring the accountability of medical drug and device manufacturers for the safety of their products, we support this new bill.

Labels: Baxter, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, MDL; Multi-District Litigation, nightline, Pallone, preemption, Scientific Protein, Scientific Protein Labs, SPL, Waxman

Zoll, Kranz & Borgess, LLC has just posted a detailed timeline relevant to the Heparin recall and subsequent litigation. This timeline created solely by Zoll, Kranz & Borgess, also features web-links to almost a hundred articles, videos, and other documents, including public documents from Baxter, SPL and the FDA. Please visit this timeline by clicking here.

Labels: Baxter, Changzhou, China, Chinese, FDA, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, Heparin Timeline, MDL, MDL; Multi-District Litigation, nightline, OSCS, Scientific Protein, SPL

The Saturday, May 31, 2008 edition of the Wisconsin State Journal ran a story on Scientific Protein Labs, the supplier of the contaminated heparin to Baxter. (SPL was formerly a division of Oscar Mayer, the hot dog company.) The story is worth reading for several reasons.

First, it describes the process involved in processing pig intestines into the raw sugar powder used to make heparin. This powder is called the api, or active pharmaceutical ingredient. Here in the United States, SPL controls its supply by actually processing the pig intestines. One 22 ton semi load of pig guts is processed down into just six pounds of heparin powder.

In China, SPL - Changzhou (SPL-CZL), an SPL joint venture, bought processed pig guts, rather than act as the parent company and purchase the raw pig guts. SPL-CZL purchased the material after some processing had been done. SPL - CZL then shipped the heparin powder in bags from China to Wisconsin. SPL did not even open the bags in Wisconsin, but simply forwarded them to Baxter's Cherry Hill, New Jersey plant. These bags contained material that had been "cut" with a counterfeit product that mimicked heparin. Up to 30% or more of the material was actually oversulfated chondroitin sulfate (OSCS).

What is new in this article is the admission that Baxter bought all of its raw heparin only from the China operation. The raw heparin that is made by SPL from domestic pigs is all sold to Sanofi Aventis, another drug company.

All of SPL's heparin was made in the United States until 2004, when it acquired the China operations. In China SPL purchases its raw materials from two different companies, and each of them obtain the processed raw material from 10 other workshops, which do the initial processing of the pig intestines. So the supply chain of SPL is much different than that here in the United States, a fact which should have been known by Baxter.

The most critical admission in the latest article is the admission by SPL that it feared suppliers would try to sell it counterfeit products because of the blue ear pig disease that was ravaging the pig supply in China. It started testing its incoming supplies to make sure that sheep intestines weren't being substituted. But amazingly it never utilized the common test of NMR until after it was too late.

It didn't even own an NMR machine.

CEO Strunce stated that he has learned a lesson. "The lesson is that you have to be constantly vigilant."

Mr. Strunce, that lesson was taught in drug manufacturing 101. You must have missed that class.

Labels: Baxter, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, MDL; Multi-District Litigation, nightline, NMR, OSCS, over sulfated chondroitin sulfate, oversulfated chondroitin sulfate, Scientific Protein Labs, SPL

Labels: Baxter, China, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, House Committee on Oversight and Government Reform, MDL, MDL; Multi-District Litigation, OSCS, over sulfated chondroitin sulfate, SPL, Stupak

Baxter held its annual meeting yesterday in Chicago. According to press reports:

Although the hourlong meeting focused on Baxter's record sales last year and rising share price, about 15 minutes was devoted to the heparin imbroglio. One investor wondered whether Baxter has taken steps to "close the loopholes" in its supply chain to make sure such a situation did not happen again.

Parkinson acknowledged "challenges associated with managing the supply chain," but that Baxter and other companies were making changes for the better.

Parkinson said Baxter and other companies get heparin's raw ingredient from China because "that's where the pig population is," adding that the Chinese supply of hogs is five times larger than in the U.S.

Well it wasn't the Chinese pigs that added oversulphated chondroitin sulphate (OSCS) to their intestines. It was someone looking to substitue a counterfeit product that was 100 times cheaper than Chinese raw heparan made from pig intestines. Someplace between the workshop that received the raw intestines and the bottling of the finished heparin, someone substituted counterfeit OSCS.

We have obtained a translated copy of a Chinese patent for the manufacture of OSCS. The Chinese patent was filed December 20, 2005 by Shandong University in Shandong China. This patent claims that OSCS can be cheaply manufactured using the claimed technique and the resulting OSCS product "has anticoagulant activity of 10 IU/mg," "anti-inflammatory and pain killing activity," and "inhibits tumor growth and metastasis."

It doesn't take a great leap of imagination to figure out that this or a similar product might be used as a substitute for heparin, particularly when disease in China had caused a sharp increase in the price of the raw product.

I commend the responsible Baxter shareholders who are challenging their company to act responsibly and "close the loopholes" that let this counterfeit product into the Baxter products.

All manufacturers of food and drug products owe a non-delegable duty to the consumers to insure the safety of their products, even if this means they have to use only those raw materials that can be securely monitored.

Labels: annual meeting, Baxter, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, MDL; Multi-District Litigation, OSCS, over sulfated chondroitin sulfate, SPL