Wednesday, March 26, 2008

Contaminated Heparin: Where is the Outrage?

We have posted frequently on the case of the contaminated heparin. A summary to date is below.

  • We have posted several times, recently here and 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 in the US was made by Baxter International.
  • We then learned that although the heparin carried the Baxter label, it was not really made by Baxter. 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.
  • Most recently, we found out that the Baxter International labelled heparin was contaminated with over-sulfated chondroitin sulfate, a substance not found in nature, but which mimics heparin according to the simple laboratory tests used in the Chinese facilities to check incoming heparin. (See post here.) Further testing revealed that the contamination seemed to have taken place in China prior to the provision of the heparin to Changzhou SPL. (See post here.) 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."

Although this case has been extensively covered by some major newspapers, with kudos going to the Chicago Tribune, New York Times, and Wall Street Journal (in alphabetical order), the story has inspired, in my humble opinion, very little commentary, and that commentary has been remarkably reticent. This week, though, some interesting points were raised in the blogsphere.

On the PharmaLot blog, Ed Silverman interviewed personal injury attorney Eric Turkewitz, who undoubtedly had some of his own axes to grind. Nonetheless, he made some points that others have not.

  • Baxter International could be in serious legal trouble - "Assuming the reports are true. Baxter sold a counterfeit drug, which is in violation of federal law. We lawyers like to call it ‘negligence per se.’ They had an obligation to verify the goods they sold are bona fide. But it appears that Baxter sold something different." Furthermore, "They have an obligation to make sure the stuff they’re selling is what they say it is. They’re the ones selling the product."
  • Baxter International executives ought to have known that deliberate counterfeiting was a potential source of contamination - "I think it’s impossible for anybody to say, with a straight face, that they’re taken by surprise by what’s happened. The dangers of counterfeiting, because of the vast sums of money at stake, are well known in the pharmaceutical industry. And one aspect of that problem is counterfeit ingredients in the production process as opposed to a counterfeit finished product that enters the supply chain in the US and is mixed in with a legitimate shipment or sold as a substitute. This is the issue with the production in China. It’s called foreseeable risk. For Baxter, I don’t know if (the sourcing) was a decision to save money or they had to look for another supplier. But whatever the reason they used this supplier, they can’t excuse it. I can’t think of any excuse (Baxter) can come up with that will hold water."

Also, Nancy Reyes, described as a retired physician living in the rural Philippines, made some points on the Blogger News Network about what commentary there has been about the case.

  • The commentary seemed to assume that the problem was due to accidental contamination, not deliberate counterfeiting - "The problem is that too many American newspapers are writing editorials as if this was merely a quality control problem that FDA inspections would eliminate." However, "The drug was deliberately diluted with a drug that would pass routine drug testing.
  • The suggested solution, more inspections, could be evaded by people who deliberately seek to sell counterfeit drugs - "Inspections won’t work. You need a full time watchdog…one who won’t accept a bribe…" Furthermore, inspections "assume honesty. But would an honest man go out of their way to find a drug that is cheap and would pass routine tests? Obviously not. And if they cheat in big things, what makes you think that the labels and paper work would be honest?" In summary, "To think that simple inspections will find the hidden corruption that allows such deliberate contamination is naive. The criminals will merely find another way to outwit the inspectors to make money. If there is to be inspections, could I suggest that the ones to do such inspections should include FBI agents familiar with organized crime?"

It seems to me that the public discourse about this case has been strangely reticent. After all, after getting intravenous heparin, patients died, and many patients got very sick. So where is the outrage? Instead, the problem seems to be discussed as if it were a natural disaster or an innocent accident, which could not have been prevented, and for which no one was to blame.

What criticism there has been was of the US Food and Drug Administration for its inadequate inspections of outsourced drug suppliers. With the exception of the interview above, there has been little criticism of the US companies who sold drugs without paying much attention to how they were produced.

Finally, almost nothing has been heard from physicians (with the recent exception of Dr Reyes). In my extensive file on this case, I have found no other commentaries written by physicians, in newspapers, and certainly not in medical journals. Maybe it just takes a long time for such things to get published.

Yet, physicians' prime obligation is to put their patients' interests first. Presumably many well-meaning physicians gave heparin to their patients assuming it was safe, pure, and more likely to do more good than harm, only to see some of them sicken, and a few die. One would think physicians would be hopping mad to find out the drug they trusted was not really made by the venerable drug company whose label adorned it, that it was really made in unknown Chinese "workshops," and was apparently deliberately contaminated long before it got to the US.

Maybe physicians are so deep into a state of learned helplessness, or so fearful of company lawyers waving SLAPPs that they can't or won't express outrage. But if we don't get mad when bad things happen, more and more bad things will happen. It is our role as physicians to stand up for our patients. So the least we can do is express our outrage when the drugs we prescribe for them turn out to be contaminated and counterfeit.

So let me say it: This case is outrageous. It demands not only a scientific, but a criminal investigation. Any people identified as responsible for contaminating the heparin, and responsible for selling the contaminated heparin without making adequate attempts to assure its purity, should be prosecuted. The negative incentives for counterfeiting drugs, and for selling drugs likely to be contaminated without adequately assessing their purity should be so strong that no one in their right mind would dare to do this again.

8 comments:

MedInformaticsMD said...

COnsidering the low quality of much of the electronics I buy stamped "Made in China", I'd say the Baxter execs should have been suspicious by default about the heparin ingredients, with regard not just to adulteration and counterfeiting (which China seems excellent at - think CD's and designer watches), but to basic impurity.

After all, these came not from a foreign electronics company, but from a foreign pig sty.

If I had been that VP for drug delivery, I'd have set up the most rigorous quality assurance program. However, that requires two things: brains and scientific education (to realize the need), and money (which cuts profits.)

I repeat, Baxter's senior executives and board should be sued, and fired.

Anonymous said...

Roy--

I'm not a physician, but I am outraged . . . and have been for quite some time, that U.S. corporations continue to prey on citizens. I've long maintained that these corporations--who have garnered the RIGHTS of personhood--should have the same accountability as persons. While I doubt that corporations could ever be charged with 1st degree murder, their complicity in wrongful deaths should attach to them criminal sanctions that accrue to individuals. Wealthy pharmaceuticals are able to incorporate large fines (multi-million dollar in nature) as a mere cost of doing business. IF and WHEN corporations (and those who lead them) are held to the same degree of criminality as individuals, nothing will change. MASSIVE FINES and IMPRISONMENT OF LEADERS, in my opinion, are the only methods that would significantly impact these miscreants. Bad publicity . . . it fades quickly. Large fines . . . the cost of doing business. Corporate integrity agreements and deferred prosecution . . . a useful delaying tactic, especially beneficial if the 'monitor' can be influenced. Loss of shareholders' equity . . . that is the most ridiculous of all--it's called GIVE THE LEADER(s) a bonus!

IMO, many doctors fail to make any connection between the erosion of public trust in the profession and their conflicted association with an industry that ALWAYS places profits above patients. Many patients DO see a connection and they also think simplistically: "Doctor (my doctor), you're either part of the solution or you're part of the problem." I think there is a large number of doctors who could benefit themselves and society by pondering this very question.


Melody

Steve said...

Roy, you are right to be outraged. Counterfeit drugs are recognized as a huge problem in other parts of the world--an estimated 100,000 people a year die in China from taking counterfeit prescription drugs. Recently, counterfeit prescription drugs have taken the lives of 19 Americans and caused severe injury to hundreds more.
Many people getting dialysis and heart surgery take large doses of heparin, a generic blood thinner. The heparin sold by Baxter International contained contaminated ingredients that were purchased from a plant in China.
It turns out that the FDA did not, as they were supposed to, investigate the Chinese plant. In fact, Rep. John Dingell, a Michigan Democrat who chairs the House Committee on Energy and Commerce, said, “Only 13 inspections were conducted in China in 2007. At this rate, it would take the FDA 55 years just to clear this backlog."
Representative Tom Bliley said, "The FDA's regulatory system used to protect Americans from counterfeit or substandard drug ingredients has significant holes." Bliley said the FDA allows the import of drugs based "merely on the representations of an international broker, who could in fact be the counterfeiter."

"The FDA admits it has information on only 18 percent of the foreign drug manufacturers shipping to the U.S," Bliley added. He reports that since 1997, some 4,600 foreign drug makers have shipped medication into the U.S. without getting inspected.
According to an article entitled, FDA Scrutiny Scant In India, China as Drugs Pour Into U.S., Broad Overseas Checks Called Too Costly, by Marc Kaufman that appeared on June 17, 2007 in the Washington Post, “Companies based in India were bit players in the American drug market 10 years ago, selling just eight generic drugs here. Today, almost 350 varieties and strengths of antidepressants, heart medicines, antibiotics and other drugs purchased by American consumers are made by Indian manufacturers.
Analysts estimate that as much as 20 percent of finished generic and over-the-counter drugs, and more than 40 percent of the active ingredients for pills made here, come from India and China. Within 15 years, they predict, as much as 80 percent of the key ingredients will come from those countries -- which are quickly becoming attractive to brand-name drugmakers, too.”
The article also states, “Over the past seven years, amid explosive growth in imports from India and China, the FDA conducted only about 200 inspections of plants in those countries, and a few were the kind that U.S. firms face regularly to ensure that the drugs they make are of high quality.
The agency, which is responsible for ensuring the safety of drugs for Americans wherever they are manufactured, made 1,222 of these quality-assurance inspections in the United States last year. In India, which has more plants making drugs and drug ingredients for American consumers than any other foreign nation, it conducted a handful.”
The FDA again proves that they don’t see their job as helping the consumer but the drug companies.
Steve Hayes
Novus Medical Detox

Anonymous said...

I am also concerned about the lack of people being outraged at this action. I can say this because I was one of the "heparin contamination" victims. At this moment, I cannot get my doctors, nor the hospital I was in to talk to me, we assume that they are worried that I will sue. But why would I sue THEM? THEY, just as I, trusted that the FDA and the drug companies would be providing a safe, clean drug, not something that would make me sicker than I already was. Luckily, I survived. Mydoctors had not expected me to. I guess only those people that were directly affected by this drug contamination are upset, maybe others are putting their head in the sand that this couldn't affect them. Because if something isn't done, something STRONG to get the attention of the FDA, drug companies, and overseas providers this will happen again. At minimum, the heads of the FDA should be fired. I mean, they have clearly NOT done their job. And if they use the excuse that they didn't have enough money to do their jobs, they should have 'rung the bell' so loud that peopl ewould listen...preisely because that IS their job. Otherwise, what is the use of having the FDA? If they are going to knowingly allow contaminated and potentially contaminated drugs and other items on our markets, then they are getting paid for doing NOTHING.
This has devestated my life. I am nothing like I was before. I apparently had such low oxygen level so long, that it has affected my brain and other organs.
Somebody needs to go to jail. if for nothing else, for the MURDER of those patients who TRUSTED their lives to the drug companies and FDA and who betrayed them. That is nothing different than a CHILD who trusted a parent to care for them and get them the medical care they need and make sure it is done and done properly.

tbrookover said...

I AM OUTRAGED. Why are we getting ANYTHING from China? They poison our kids toys....our pets food...and now medications that WE in the USA are quite capable of making. My Mom received heparin in Jaunary of this year and died. I do not yet know if she received the bad batch or not...but trust me I am trying to find out. The fact is she had an episode of pulmonary edema...and was very ill anyway. The treatment CAUSES low blood pressure...but she has been through this so many times.....without incident. If she received the bad batch....how on earth could she have ever fought that off since it caused low blood pressure. I am just beside myself...and I will tell you this...if I find out she received the bad haparin...I plan on making so much noise about getting this stuff from China...that the whole world will hear me. I am outraged....even if we find out my Mom did not receive it...I am STILL OUTRAGED.

Anonymous said...

My mother passed away on September 13th after developing what was described as heparin induced thrombosis in both of her arms. One of the blockages was so severe that the doctors determined that they needed to surgically remove the offending clot. Immediately after surgery, her blood pressure dropped drastically and she suffered 4 cardiac events, the last of which was fatal.
I don't know where to start with investigating whether the heparin she received was from the lot imported by Baxter from China. If I were to inquire on my own, I would probably receive little cooperation from the hospital, and I don't have the funds to hire a lawyer. I can't get my mother back, but would like something to be done about the lack of concern displayed by the FDA and other agencies intrusted with protecting the health of Americans. Anything coming into the United States from China should be screened extensively, considering their bad track record.

Anonymous said...

I wonder if companies are using foreign (China and other Asian countries) to make medicines in an attempt to fly under the radar and avoid the FDA and it's stringent, heavy regulation and inspection of drug manufacturers. Obviously, the FDA cannot inspect everything to do with medicine production in these foreign countries, and money is being made selling the imported medicines at users' risk. Why doesn't the FDA ban imported medicines or stop them at the border until sufficient inspection and testing of the substance can be made? We can't purchase Canadian medicines (that originally were made here and shipped there.) But we can purchase foreign made junk?
Is the answer powerful Lobbyists?

Anonymous said...

why have no criminal charges been filed yet?