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

In a statement released July 10, 2008, Texas Hospital, Christus Spohn, indicated that the recent heparin overdose of 17 children in its Neonatal Intensive Care Unit, was a result of an error that occurred during the mixing process in its hospital pharmacy. (See 07/10/08 Christus Spohn Statement.) While the hospital claims this mistake in mixing was unrelated to product labeling or packaging, (which has recently resulted in similar deaths), it has not released details as to how the “mixing error,” occurred.

Likewise, in true defense fashion, the Texas Hospital is quick to speculate publicly that the heparin overdose of twins Keith and Kaylyn Garcia, (which was 100 times stronger than recommended), did not directly result in their deaths, before the conclusion of any autopsies. Relatives of the twins had planned a baby shower for their mother today, instead their funerals will be held. (7/11/08 ABC news, “Hospital Error Blamed for More Infant Overdoes.”)

If hospitals spent as much time figuring out ways to eliminate and reduce errors, as setting up defenses to protect themselves from anticipated future litigation, we would all be safer.

Labels: Baxter, Christus Spohn, Dennis Quaid, heparin attorney, Heparin Class Action, heparin lawsuit, heparin mixing error, kaylyn garcia, keith garcia, nightline, Scientific Protein Labs

Labels: Abel, Baxter, Best, Charles, Connaught, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, Heparin Timeline, Howell, Johns Hopkins, McLean, MDL, Murray, nightline, over sulfated chondroitin sulfate, Scientific Protein Labs, Scott

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

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

Labels: Baxter, CDRH, China, Chinese, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, MDL, nightline, OSCS, over sulfated chondroitin sulfate, Scientific Protein Labs

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

• Heparin lock flush solutions in vials and solutions in pre-filled syringes;
• Devices used during cardiopulmonary bypass procedures, including certain oxygenators, filters, reservoirs, and cannulae;
• Catheters including certain vascular access catheters, drainage, retransfusion and thermodilution catheters, and oximetry probes;
• Certain vascular stents and grafts;
• Certain assisted reproduction media devices; and
• Certain In-Vitro Diagnostic media and related devices

A list of other medical devices and diagnostic products that may contain or be coated with heparin can be found by clicking here. This list also includes the manufacturer or distributor.

Labels: American Health Packaging, B. Braun, Baxter, Covidien, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, heparin medical device, Medtronic, nightline, over sulfated chondroitin sulfate, Scientific Protein Labs

Labels: Baxter, China, Dennis Quaid, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, House Committee on Oversight and Government Reform, MDL, MDL; Multi-District Litigation, nightline, OSCS, over sulfated chondroitin sulfate, preemption, Scientific Protein Labs

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