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

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

One of the key issues in the Heparin Disaster litigation is whether Baxter and SPL should have taken reasonable steps to insure the safety and purity of the raw materials used in the finished heparin product.

We now know that a test called NMR Spectroscopy can easily distinguish over sufated chondroitin sulfate ("OSCS") contaminated heparin from the real thing. So what is NMR Spectroscopy?

According to Wikipedia:

Nuclear magnetic resonance spectroscopy, most commonly known as NMR, is the name given to a technique which exploits the magnetic properties of certain nuclei. This phenomenon and its origins are detailed in a separate section on nuclear magnetic resonance. The most important applications for the organic chemist are proton NMR and carbon-13 NMR spectroscopy. In principle, NMR is applicable to any nucleus possessing spin.

Many types of information can be obtained from an NMR spectrum. Much like using infrared spectroscopy to identify functional groups, analysis of a 1D NMR spectrum provides information on the number and type of chemical entities in a molecule.

The impact of NMR spectroscopy on the natural sciences has been substantial. It can, among other things, be used to study mixtures of analytes, to understand dynamic effects such as change in temperature and reaction mechanisms, and is an invaluable tool in understanding protein and nucleic acid structure and function. It can be applied to a wide variety of samples, both in the solution and the solid state.

Over the past 50 years NMR has become the preeminent technique for analysis of organic compounds. Here is a very good explanation (with pictures!) as to how NMR works from an undergraduate level course in Organic Chemistry at Michigan State University:

NMR Spectroscopy

While the science and theory maybe complex to a layman, NMR has been around a long time and is a very common analysis method taught at the undergraduate level. We intend to find out from Baxter and SPL why they failed to use this common test method in the analysis of raw materials from unknown sources before inclusion in such an important and sensitive product as heparin.

We continue to investigate cases from patients or their families around the country who have been killed or injured by this counterfeit product.

Labels: Baxter, Heparin, heparin attorney, Heparin Class Action, heparin lawsuit, heparin lawyer, MDL, MDL; Multi-District Litigation, NMR, nuclear magnetic resonance spectroscopy, OSCS, over sulfated chondroitin sulfate