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

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

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

On Monday, during an interview with The Associated Press, U.S. Health and Human Services Secretary, Mike Leavitt, represented that the heparin in the United States is now safe in light of tighter testing and controls. (5/12/08 Chicago Tribune Article: “U.S. Health Secretary: Chinese Heparin Now Safe.”) He discussed the additional guidelines regarding quality and safety that exporters must now meet. I hope he is right. I hope that after months of Americans dying from contaminated heparin, import alerts at the borders and proper testing, heparin and all drugs coming into the United States are now safe. (Although based on the evidence presented to the U.S. House Commerce Committee on Energy and Commerce at the April 29, 2008 hearing entitled, “The Heparin Disaster: Chinese Counterfeits and American Failures,” I doubt this is the case.) But what about what is on our shelves already?
Unfortunately, just a week ago, the FDA stepped up its heparin alert to hundreds of hospitals, medical societies and pharmaceutical organizations after learning that some medical facilities still had contaminated heparin among their supplies. (5/9/08 Wall Street Journal, “FDA Issues Update Heparin Alerts to Medical Facilities.”) The notice to the facilities read, "Please help FDA spread the word about recalls of injectable heparin products and heparin flush solutions that may be contaminated with oversulfated chondroitin sulfate (OSCS). Affected heparin products have been found in medical care facilities in one state since the recall announcement…Although product recall instructions were widely distributed, they may not have been fully acted upon at all sites where heparin is used.”
Indeed, many manufacturers and distributors of medical products containing or coated with heparin have only recently begun to identify and recall products containing the contaminant, as requested by the FDA last month. For example, on Monday, Atrium Medical Corporation recalled selected lots of HYDRAGLIDE™ Brand Heparin-Coated Thoracic Drainage Catheters that were manufactured with heparin that was contaminated with OSCS. Likewise, on May 7, 2008, Medtronic, Inc. recalled selected products with a “Carmeda BioActive surface” that were manufactured with heparin found to have been contaminated with OSCS. The affected devices are disposable products used during cardiopulmonary bypass (CPB) for heart surgeries. Affected products include blood oxygenators, reservoirs, pumps, cannulae, and tubing packs.
This delayed response is unfortunately consistent with the experience of our clients, some of whom we believe received recalled heparin after the date of recall, or who never received notice of the recall from their pharmacy or medical facility. Authorities must continue to focus not only on what is being imported, but what is already within our borders. A blanket promise of safety to the unsuspecting American public should only be made when it is certain that it is a promise that can be kept.

-Submitted by Pamela A. Borgess

Labels: Atrium, Baxter, Changzhou, China, Chinese, FDA, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, Leavitt, MDL, MDL; Multi-District Litigation, Medtronic, OSCS, over sulfated chondroitin sulfate, oversulfated chondroitin sulfate

The director of China's "FDA" told a press conference that Baxter had failed to cooperate with Chinese experts sent to the U.S. to investigate the Heparin Disaster. The director, Jin Shauhong, also claimed that there was no "confirmed" link between the Over Sulfated Chondroitin Sulfate ("OSCS") and the deaths of patients in the United States.

Chinese representatives 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. Baxter now says it will give the Chinese samples of the product to test.

The FDA tried to inspect the Changzhou Techpool Pharmaceutical Co. ("CZTP") in Changzhou, China on February 27, 28 and 29, 2008. This company supplied SPL Changzhou with raw heparin and may have been a source for the contaminant.

During those inspections the FDA was accompanied by a representative of the U.S. Embassy from Beijing. This facility was NOT regulated by the Chinese because it did not sell any product within China. Instead its products were all made for export; therefore neither the Chinese nor the FDA inspected this plant.

Changzhou SPL, a defendant in the cases we have filed, owns 45% of CZTP. During the FDA inspection CZTP refused to provide the FDA with records for review.

Now the Chinese are complaining that U.S. companies are not cooperating with them in their investigation. What a surprise.

This illustrates a number of critical shortcomings in our drug system. First, as admitted by the FDA last week, the FDA is woefully underfunded and unable to inspect foreign manufacturers. Second, the manufacturers themselves cannot be relied upon to self-regulate their suppliers. Third, China and the United States have been unable to cooperate with each other to insure that good manufacturing practices are followed throughout the chain.

The only regulation that is truly reliable is that obtained by our common law. Companies that fail to insure the safety of ingredients in their products must be held strictly accountable for all injuries and deaths they cause. They must be held strictly accountable.

SPL used to be called Oscar Mayer. It used the small intestines of American grown hogs to make the raw heparin. There was no adulteration by counterfeit heparin because Oscar Mayer was an American company with a reputation to protect and a business to run. It would be unthinkable.

Yet somewhere along the way, through free trade agreements, the drive for ever higher shareholder return, corporate profits, deregulation, and business - friendly agencies we have lost our way. As we go through the documents and take the depositions of these corporate officers we are going to learn a lot more. And it isn't going to be a pretty picture.

By the way, if the Chinese are really worried about the relationship between the counterfeit heparin and the injuries and deaths, I suggest they read the recent article in the New England Journal of Medicine. We have a link to it on our web site. Maybe we should translate it into Mandarin.

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