Fake Heparin, then Sick and Dead Patients

We have posted several times, most recently here, about the tragic case of suddenly allergenic heparin. Although heparin, an intravenous biologic anti-coagulant, has been in use for over 70 years, serious allergic reactions to it had heretofore been rare. Starting late last year, hundreds of such reactions, and now 21 deaths were reported in the US after intravenous heparin infusions. All the heparin related to these events was made by Baxter International.

We then learned that although the heparin carried the Baxter label, it was not really made by Baxter. In fact, the company had outsourced production of the active ingredient to a long, and ultimately mysterious supply chain. Baxter got the active ingredient from a US company, Scientific Protein Laboratories LLC, which in turn obtained it from a factory in China operated by Changzhou SPL, which in turn was owned by Scientific Protein Laboratories and by Changzhou Techpool Pharmaceutical Co. Changzhou SPL, in turn, got it from several consolidators or wholesalers, who in turn got it from numerous small, unidentified "workshops," which seemed to produce the product in often primitive and unsanitary conditions. None of the stops in the Chinese supply chain had apparently been inspected by the US Food and Drug Administration nor its Chinese counterpart.

It is not clear whether Baxter International or Scientific Protein Laboratories had inspected most of the steps in the supply chain, or even knew what went on there. The Baxter and Scientific Protein Laboratories CEOs did not seem aware of where they got the heparin on which the Baxter International label was eventually affixed. But one report in the New York Times alleged that Scientific Protein Laboratories would not pay enough for heparin to satisfy any sources other than the small "workshops."

Now the US FDA just reported it identified a contaminant in the heparin that may be responsible for the adverse reactions. This has already been reported today by many media outlets, but I will quote Bloomberg since its article makes the main points most concisely,

Baxter International Inc.'s blood thinner heparin, linked to deaths and allergic reactions, was contaminated with a less-expensive ingredient derived from animal cartilage, U.S. regulators said.

The contaminant, over-sulfated chondroitin sulfate, isn't approved for use in medicine, said Janet Woodcock, the head of the Food and Drug Administration's drug division, in a conference call today with reporters. Regulators are investigating whether the substance was intentionally or accidentally added to raw heparin from China.

'It does not appear to have come straight from the pig,' Woodcock said of the contaminant. 'It doesn't appear to be a natural contaminant that got in there. We don't know how it was introduced or why.'

Adding the contaminant to raw heparin, the active ingredient in the finished product, would have been cheaper than using pure raw heparin, according to the FDA. The agency didn't know how much money would be saved by its use, Woodcock said.

Chondroitin sulfate is taken orally as a dietary supplement to treat joint pain. The over-sulfated version found in the heparin was chemically modified to act like heparin, Woodcock said.

Over-sulfated chondroitin sulfate is generated in laboratories for experimental purposes, said Siobhan DeLancey, an FDA spokeswoman, in an interview. It is chemically altered to add additional sulfates, she said.

Two percent to 50 percent of the contaminated raw heparin samples tested by the FDA were made up of over-sulfated chondroitin sulfate, Woodcock said.

So it now appears, although it is not yet proven that the adverse reactions and deaths were caused not by a trace contaminant derived from a sloppy, primitive, and unsanitary manufacturing process, but from a bulk counterfeit ingredient deliberately introduced because it was cheaper than heparin, yet would fool purchasers into thinking it was heparin.

Thus we see what happens when US health care leaders were happy to put their prestigious logo on a drug whose source was unknown to them, presumably just to save some money. By obviously failing to exert rigorous oversight over how the drug which carried their company's name was produced, they not only allowed sloppy, primitive and unsanitary manufacturing practices, but apparently were easily snookered by counterfeiters who substituted a likely toxic ingredient for the real thing.

This was putting profits before patients. And the results were very bad for patients.

Baxter claims to apply

its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients' lives.

However, rather than its expertise, its sloppy and uncaring leadership seemed to leave some of its patients' lives meaningfully worse.

This case is a glaring demonstration of why we need a new set of leaders of our health care organizations, and a new corporate culture within these organizations. Otherwise, failing to understand the health care context, and failing to put patients before profits will yield more sick and dead patients.