Tuesday, August 30, 2011

JAMA Article Begs Key Questions About Case of Contaminated Heparin

There was a recent reminder of the case of the tainted heparin, which begged more questions than it answered.  (A case summary is appended to the end of this post, and nearly all our posts are here.)  The case is of fundamental importance because it involves the failure of pharmaceutical companies to fulfill their core mission, to supply pure, unadulterated drugs.   Three years later, how the heparin was adulterated, and who was responsible are still unknown.
JAMA just published a major news article (Kuehn BM. As production goes global, drug supply faces greater risks to safety, quality.  JAMA 2011; 306: 811-813.  Link here.) This, in turn, was based on a five page case study of the heparin incident in a report by the Pew Health Group entitled "After Heparin: Protecting Consumers from the Risk of Substandard and Counterfeit Drugs" (link here).  Reading between the lines, the Kuehn article raised several questions which it did not seek to answer, but which we have raised previously.

Why Didn't Baxter Look the Gift Horse in the Mouth?

The JAMA article noted that in general, "pharmaceutical companies are shifting the production of drugs and drug ingredients to emerging economies - primarily India and China - to save money."  [italics added for emphasis]  Also, "Many emerging economies do not have robust regulatory systems, and regulators from the United States or other countries may face hurdles in trying to oversee production in these nations."

Why were Baxter International executives not concerned about the quality of a drug offered cheaply from firms in countries with little regulatory oversight? 

Note that we have been asking versions of this question since 2008, e.g., "How hard did Baxter scrutinize the production of the drug? How hard did SPL scrutinize its production? Did Baxter, SPL and/or the FDA realize the drug was being produced in an unlicensed Chinese chemical factory which had never been inspected by the Chinese or US government? If they did, why did they accept its product? If they didn't, why didn't they know?" - from this post on February, 16, 2008.

Who Is Responsible for the Complexity and Opacity of the Out-Sourced Supply Chain?

The article stated, "In addition to becoming more global, the drug supply chain has also become more complex, .... Drug ingredients are now imported from 150 countries, and multiple suppliers, producers, and distributors may be involved in the production and import of a single drug." 

In particular, the article noted that "Baxter relied on the assessment of another company when it began receiving heparin from the plant through which the adulterated drug came."  (The nameless other company was Scientific Protein Laboratories.)  Also, it noted that the supply chain began at "the primitive workshops that extract heparin crude by cooking and drying pig intestines" and proceeded to "the companies that consolidate materials from many such workshops and sell them to the factories that produce heparin."  The article did not discuss how this particular supply chain came into existence.

Did not drug companies in developed countries, like Baxter International in this case, create these convoluted supply chains (mainly to save money, as noted above)?  If not, did they not at least enable the creation and operation of these chains by purchasing their products without asking too may questions?  In any case, the supply chain's complexity and opacity arose out of individual humans' decisions, not an act by a deity. 

Why Have no Individuals Been Held Accountable? 

The article noted that the Pew report suggested, "increasing the financial penalties and allowable prison terms for individuals and companies who violate the rules from their current maximums of $10 000 or 3 years in prison." The implication was that these penalties have proven insufficient.  However, the article failed to note that so far in the case of the tainted heparin, no such penalties have even been sought.  To my knowledge, neither Baxter International, Scientific Protein Laboratories, nor any individual who worked for them has ever been charged with any violation of "the rules" that could result in any penalty as much as "$10 000 or 3 years in prison."    I have asked repeatedly why so far there has been no obvious effort to hold any individual accountable for the contaminated heparin?  (see this post from July 19, 2010, in which I noted legal actions against doctors who implanted IUDs imported from and approved in Canada and asked, "why are we so vigorously pursuing individual doctors for an apparently technical violation of laws that did patients no apparent harm, when we are not pursuing health care corporate executives for selling adulterated drugs that likely killed patients? 

Why Are the Key Issues In This Case Still So Anechoic?

Neither the JAMA article nor the heparin case study in the underlying Pew report directly addressed these questions.  The JAMA article also omitted such details as the name of the company from which Baxter directly purchased the heparin (Scientific Protein Laboratories) and the total number of deaths that may have been related to the heparin.  (It only mentioned 3 deaths related to heparin, while the Pew Report noted the FDA got reports of 68, six more of which it allowed were "possibly caused by the adulterant, 24 were unlikely, and 35 were unassessable.")  As mentioned above, the JAMA article seemed to imply that criminal penalties have been applied to corporate executives whose companies may have profited from cheap but defective out-sourced drugs (but none have been applied in the heparin case).   Ironically, while the JAMA article identified the "culprit" for the adverse events in the heparin case, it used the word to refer to the compound that adulterated the heparin, not those who added it, or who enabled its addition. 


Thus, the public discussion in the main-stream medical media of the case of the adulterated heparin is still remarkably squeamish even three plus years after it first became public.  While the heparin case has made it into major medical journals, it still simply is not done to even publicly discuss whether the leaders of health care organizations who become rich partly as a result of decisions such as the unsupervised, uninspected, apparently barely considered out-sourcing of heparin to be accountable when these decisions turn out to have adverse effects on patients.

If we cannot even discuss the accountability of leaders of health care organizations, how can we hope to actually hold them accountable?  

To repeatedly reiterate, as long as the leaders of health care organizations are not held accountable for the results of their decisions on health care quality, cost, and access (even in such extreme quality violations as those resulting in multiple patient deaths), we can expect continuing decisions that sacrifice quality, increase costs, and worsen access, but that are in the self-interest of the people making them.

To really reform health care, we must hold health care organizations and their leaders accountable (and not blame all the problems on doctors, other health care professionals, patients, and society at large).

Case Summary

- We have posted several times, 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 in 2007, hundreds of such reactions, and 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. (See posts here and here.)

- 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."

- Leaders of all organizations involved, Baxter International, Scientific Protein Laboratories, Changzhou SPL, the Chinese government, and the US Food and Drug Administration, and the US Congress assigned blame to each other, but none took individual or organizational responsibility. (See post here.)  Note that SPL was recently bought out and taken private, making its current leadership even less transparent (see post here).  A 2010 inspection of an SPL facility by the FDA revealed ongoing manufacturing problems (see post here).

- Researchers (who turned out to have financial ties to a company which is developing an anti-coagulant drug that could compete with the heparin made by Baxter International) investigated the biological mechanisms by which the contamination of the heparin lead to adverse effects, but no one investigated further how the contamination occurred, or who was responsible. (See post here.)

- Hundreds of lawsuits against Baxter have now been filed, so far without resolution. (See post here.)  Efforts to make documents to be used in these cases public so far have not succeeded (see post here).

- A government report which attracted little attention warned of the dangers of pharmaceutical ingredients made in China and subject to virtually no oversight. (See post here.)

-  Despite requests from the US, the Chinese government did not investigate the production of the heparin that lead to the deaths (see post here.)

-  In February, 2011, a congressional investigation of the case was announced, but results are so far unavailable (see post here.)

-  In June, 2011, a jury returned the first verdict in a civil case about the contaminated heparin, awarding money from Baxter International and Scientific Protein Laboratories to the estate of a man who apparently died due to tainted heparin (see post here).


Steve Lucas said...

Today while driving around I heard on the radio a report that generic drugs have become difficult to find. It seems that this is due to the drug companies not making enough profit.

Our two local hospitals, who have had a number of legal actions against one another, now find they must share scarce cancer drugs.

So the question is no longer can I make a profit from a drug, but can I make more profit on other drugs, and drop this drug from my production schedule.

We have reached the point where profit is the only thing that matters, and commitment to patient care and safety does not exist.

Steve Lucas

Anonymous said...

It is interesting how healthcare reform in the Obama administration was derailed. Policy wonk types have little understanding of what really goes on. Normally they simply accept what these corporations tell them as if there is no reason to disbelieve.

Anonymous said...

There are lots of unanswered questions that even the people with the heparin lawsuits can't get answers to.We are told there are gag orders on everything.The trial dates keep getting put off.What is being offered for settlements are so low then you have to pay your lawyer out of it.Its like a slap in the face of the People who lost loved ones to Heparin.We are told since your loved one that died was a senior citizen they are not worth anything.If hiring someone to kill for you is illegal,what is the difference? Cheap,lethal drugs are no less than murder for profit.

Anonymous said...

This thing with heparin should of been out in the news for everyone to see . people have the right to know what is going on in the med.world. IT is really a shame when you have a lawyer and get no answers to questions you ask. IT as if they only tell you what they want you to know. Lawyers work for you ,you do not work for them.Heparin is one of the worst thing that happen and really know one really knows to much about it . SO lets all let everyone know what really happen.

Anonymous said...

An early proposed 'solution' was to set up FDA offices in foreign countries. What a terrible expenditure of taxpayer monies. The FDA is charged with protecting Americans. If a company chooses to use a foreign source/manufacturer for the drugs it peddles to Americans, then the buck should stop with the corporation. And since corporations are now 'people', I suggest that they be treated as such. Both life in prison and the death penalty serve as deterrents/punishments for individuals; let them also serve our corporate 'people.' If a few companies were 'executed', or prevented from doing business in America, perhaps higher-ups in other corporations would get the message.

I know--look forward, not back!


Anonymous said...

Heparin, What can I say about baxter getting away with what they have done to so many people. We have lost loved ones that should still be here. People have been hurt and the companies don't care what happen. They made there money and have kept this lawsuite out of the public eye for so long. We ask questions and get no answers its just like no one cares. The head of the drug companys should be treated just like any other american if you do wrong you should be put in jail. So many people in the drug company knew what was going on it must be they have no since of right or wrong or just didn't care what this drug could do to people. I my self would like to see them put in prison for a very long time. I know it would not undo what their drug did but it would help.

Anonymous said...

My mother lost her life to heparin, and a part of me went with her. She suffered for three years before she died, and for those three years she lived in hell. She suffered so greatly as she did not want to give up her life or leave her family. She was still young, and had grand kids to meet. I am so angry at what has been done, and now we are being offered settlements that are less than the profits that were made off of the criminal activity that caused our loved ones to die. We need to band together or Baxter and other companies will continue to get away with murder, and still make a profit. We must do something to make our voices heard. There is power in numbers, and love always triumphs, right? I do not want my mother's death to be for nothing. American citizens need to be made aware of what is happening, and where our drugs are coming from. I know that my mother would have never accepted drugs from China if there had been full disclosure. We need to make sure this does not continue to happen to other innocent people.