Baxter, China and Toxic Heparin

Eighty-one deaths in the United States have been linked to allergic reactions to a Chinese-concocted contaminant in the widely used blood thinner heparin. The contaminant is an animal cartilage-derived oversulfated chondriotin sulfate. This ersatz non-FDA-approved chemical poorly mimics heparin but costs one one-hundredth of the price of legitimate heparin.

Last month, FDA Commissioner Andrew Von Eschenbach told the US Senate that the replacement of heparin was not inadvertent, but an intentional act that was by “virtue of economic fraud.”

This fraud joins several recent Chinese-initiated toxic chemical substitutions executed to save money for the Chinese suppliers while ultimately costing their American counterparts billions of dollars in litigation expenses and product recalls.

The recalls included tainted pet food that killed hundreds of pets, after Chinese suppliers substituted melamine for wheat gluten; nephrotoxic melamine is cheaper than wheat gluten and is difficult to detect. Fake Colgate toothpaste was found contaminated with antifreeze that can cause kidney failure, convulsions, coma, or even death. There was excessive lead in paint on toys made in China that forced Mattel and other US toymakers to remove millions of toys from stores.

In addition, there are over 350,000 web sites selling fake Chinese-manufactured Viagra and other fake US patented medicines to unsuspecting consumers who think they are purchasing the real thing.

Where is the FDA in all these shenanigans? Apparently, nowhere.

In the case of the toxic heparin, the FDA never even inspected the facility making the active pharmaceutical ingredient [API] for heparin. Since 75% of all API’s used by pharmaceutical companies are imported mainly from China and India, the FDA must have an effective yet timely response system to inspect proposed API facilities.

Not only does this not exist, but also the FDA lacks funding to carry out its inspection duties. It is estimated that the FDA needs to spend $225 million on foreign plant inspections every other year. The FDA is budgeted $9 million.

The time between plant inspections in the US is two years. In China, it is presently thirty years. This is because there are only 20 API facility visits per year to China for their 714 API facilities, which comes to a 30 years average time span between visits.

In China, this does not include chemical manufacturers who may supply chemicals to the pharmaceutical industry. In this case, the Chinese FDA, the State Food and Drug Administration [SFDA] does not register the companies as API’s. Thus, they are exempt from Chinese SFDA regulations because they are classified as chemical manufacturers.

And it was an exempt chemical manufacturer, Changzhou SPL Company Ltd., who supplied adulterated heparin to Baxter (BAX)-- the pharmaceutical company that supplies the vast majority of heparin used in the United States.

When the FDA finally got around to inspect the manufacturing facility of Changzhou SPL, on a 5-day visit ending on February 26, 2008 there were numerous serious violations noted. The gist of FDA investigator Regina Brown’s report is summarized:

There were no critical processing steps identified for Heparin Sodium. There were no documented steps identified for the removal of toxins such as heavy metals, bacteria, endotoxins and other impurities. There were no annual test results available. Basic written records such as set temperature and times as well as user observations during the manufacturing process was not recorded. When lots were tested and failed various tests such as the Nitrogen Determination Test, the investigations were recorded as being complete when in fact there was no determination recorded of why the sample failed the test in the first place. There was no impurity profile established for Heparin Sodium USP and no evaluation for degradants during stability program testing. An unacceptable (to the FDA) workshop vendor sold ingredients used in the manufacture of Heparin Sodium. The inside surface of large, "cleaned” tanks used in the final ?manufacturing? step, after both were very scratched, with unidentified material adhering to the insides and the tanks’ inverted handles held liquid, which spilled to the bottom of the tank when it was up righted. There was no written procedure showing that the tanks were dedicated to a particular process step. Raw material inventory records as well as waste records were incomplete.

The shortcomings noted on the inspection report of Changzhou SPL Company Ltd. were so onerous, the FDA banned Chinese heparin imports into the United States. But this latest episode of the FDA not enforcing its own quality controls (until Americans die) belie the FDA’s ability to protect Americans from substandard manufactured drugs. If you buy any other product in the United States such as a car, toy or appliance, the country of origin must be displayed. Why is there no such disclosure for prescription drugs?

Many prescription medicines that United States consumers buy are composed of active ingredients made in China. I wonder how many Americans would feel safe swallowing medicines coming from a country with the lowest quality control standards in the world.

Made in China? Now that’s a bitter pill to swallow.

Comments

[huangthomas]

Crude heparin extract is a by-product of making shells for sausage from pig small intestine. Therefore, it is a byproduct of a food manufacturing process. Everyting is hadled as a food processing and the places are filthy. Baxter knew it from the very beginning. The final steps of purification of heparin performed in the US is a very effective ion exchange process. Because it is so powerful that Baxter neglected the initial manufacturing processes. Intentional criminal addition of superfulfated chondroitin sulfate was entirely unexpected by anyone. In China, everything is possible and all products should be tested before accepted. The test costs 17 cents per dose dispensed to the patient. I believe all heparin crude extract imported to the United States should be tested.

[huangthomas]

The effectiveness of FDA inspection has been over stated. FDA can only assure a good manufacturing practice, but cannot catch a thief pouring toxic brew into the product in a fraction of a second. This is more of a job for FBI or police department. FDA deserve more money, but not for this reason. It is less expensive to just test the crude products before entering the United States.