Another Echo of the Case of the Deadly Heparin - A Report on the Perils of Out-Sourcing Drug Production

In 2008, we published multiple posts on how heparin made as an "active pharmaceutical ingredient" in China under apparently primitive conditions, contaminated accidentally or deliberately, was sold in the US bearing the label of a large American pharmaceutical company.  Ultimately, many patients were sickened, or died.  A summary of our posts on the topic, in smaller type, is below.

Case Summary

- 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."

- 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.)

- 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.)

Now, as reported to date only on the PostScript blog, a US government report on problems with active pharmaceutical ingredients made in China has appeared.

A new report (pdf) by the U.S. China Economic and Security Review Commission stresses the safety risks to Americans posed by pharmaceutical ingredients made in China.

According to the report, issued by a group that advises Congress on the economic and trade implications of U.S.-China relations, found that the U.S. is the number one destination for Chinese pharmaceutical raw material exports – a $2.2 billion business each year. The U.S. relies heavily on Chinese products not only for over-the-counter drugs but for active pharmaceutical ingredients (API) found in prescription drugs.

And the report makes clear that China has neither the will nor the systems in place to monitor its exports.

This begs the question that most of the coverage of the deadly heparin also begged.  Are American pharmaceutical companies so besotted with the need for cost-savings that they are willing to buy active pharmaceutical ingredients with unknown provenance overseas as if they were a pig in a poke?  If so, why do we allow company leadership to potentially sacrifice quality, and sell adulterated drugs just to enrich their bottom lines (and their executives' salaries)? 

Dinner with Taubes, Eades and Hujoel

Gary Taubes gave a lecture at UW last Thursday. Thanks to all the Whole Health Source readers who showed up. Gary's talk was titled "Why We Get Fat: Adiposity 101 and the Alternative Hypothesis of Obesity". He was hosted by Dr. Philippe Hujoel, the UW epidemiologist and dentist who authored the paper "Dietary Carbohydrates and Dental-Systemic Diseases" (1).

Gary's first target was the commonly held idea that obesity is simply caused by eating too much and exercising too little, and thus the cure is to eat less and exercise more. He used numerous examples from both humans and animals to show that fat mass is biologically regulated, rather than being the passive result of voluntary behaviors such as eating and exercise. He presented evidence of cultures remaining lean despite a huge and continuous surplus of food, as long as they stayed on their traditional diet. He also described how they subsequently became obese and diabetic on industrial foods (the Pima, for example).

He then moved into what he feels is the biological cause of obesity: excessive insulin keeping fat from exiting fat cells. It's true that insulin is a storage hormone, at the cellular level. However, fat mass regulation involves a dynamic interplay between many different interlacing systems that determine both overall energy intake and expenditure, as well as local availability of nutrients at the tissue level (i.e., how much fat gets into your fat tissue vs. your muscle tissue). I think the cause of obesity is likely to be more complex than insulin signaling.

He also offered the "carbohydrate hypothesis", which is the idea that carbohydrate, or at least refined carbohydrate, is behind the obesity epidemic and perhaps other metabolic problems. This is due to its ability to elevate insulin. I agree that refined carbohydrate, particularly white flour and sugar, is probably a central part of the problem. I'm also open to the possibility that some people in industrial nations are genuinely sensitive to carbohydrate regardless of what form it's in, although that remains to be rigorously tested. I don't think carbohydrate is sufficient to cause obesity per se, due to the many lean and healthy cultures that eat high carbohydrate diets*. Gary acknowledges this, and thinks there's probably another factor that's involved in allowing carbohydrate sensitivity to develop, for example excessive sugar.

I had the opportunity to speak with Gary at length on Thursday, as well as on Friday at dinner. Gary is a very nice guy-- a straightforward New York personality who's not averse to a friendly disagreement. In case any of you are wondering, he looks good. Good body composition, nice skin, hair and teeth (apologies to Gary for the analysis). Philippe and his wife took us out to a very nice restaurant, where we had a leisurely four-hour meal, and Dr. Mike Eades was in town so he joined us as well. Mike has a strong Southern accent and is also a pleasant guy. Philippe and his wife are generous and engaging people. It was a great evening. The restaurant was nice enough that I wasn't going to be picky about the food-- I ate everything that was put in front of me and enjoyed it.


* I'm talking about prevention rather than cure here. I acknowledge that many people have had great success losing fat using low-carbohydrate diets, including two gentlemen I met on Thursday.

Dinner with Taubes, Eades and Hujoel

Gary Taubes gave a lecture at UW last Thursday. Thanks to all the Whole Health Source readers who showed up. Gary's talk was titled "Why We Get Fat: Adiposity 101 and the Alternative Hypothesis of Obesity". He was hosted by Dr. Philippe Hujoel, the UW epidemiologist and dentist who authored the paper "Dietary Carbohydrates and Dental-Systemic Diseases" (1).

Gary's first target was the commonly held idea that obesity is simply caused by eating too much and exercising too little, and thus the cure is to eat less and exercise more. He used numerous examples from both humans and animals to show that fat mass is biologically regulated, rather than being the passive result of voluntary behaviors such as eating and exercise. He presented evidence of cultures remaining lean despite a huge and continuous surplus of food, as long as they stayed on their traditional diet. He also described how they subsequently became obese and diabetic on industrial foods (the Pima, for example).

He then moved into what he feels is the biological cause of obesity: excessive insulin keeping fat from exiting fat cells. It's true that insulin is a storage hormone, at the cellular level. However, fat mass regulation involves a dynamic interplay between many different interlacing systems that determine both overall energy intake and expenditure, as well as local availability of nutrients at the tissue level (i.e., how much fat gets into your fat tissue vs. your muscle tissue). I think the cause of obesity is likely to be more complex than insulin signaling.

He also offered the "carbohydrate hypothesis", which is the idea that carbohydrate, or at least refined carbohydrate, is behind the obesity epidemic and perhaps other metabolic problems. This is due to its ability to elevate insulin. I agree that refined carbohydrate, particularly white flour and sugar, is probably a central part of the problem. I'm also open to the possibility that some people in industrial nations are genuinely sensitive to carbohydrate regardless of what form it's in, although that remains to be rigorously tested. I don't think carbohydrate is sufficient to cause obesity per se, due to the many lean and healthy cultures that eat high carbohydrate diets*. Gary acknowledges this, and thinks there's probably another factor that's involved in allowing carbohydrate sensitivity to develop, for example excessive sugar.

I had the opportunity to speak with Gary at length on Thursday, as well as on Friday at dinner. Gary is a very nice guy-- a straightforward New York personality who's not averse to a friendly disagreement. In case any of you are wondering, he looks good. Good body composition, nice skin, hair and teeth (apologies to Gary for the analysis). Philippe and his wife took us out to a very nice restaurant, where we had a leisurely four-hour meal, and Dr. Mike Eades was in town so he joined us as well. Mike has a strong Southern accent and is also a pleasant guy. Philippe and his wife are generous and engaging people. It was a great evening. The restaurant was nice enough that I wasn't going to be picky about the food-- I ate everything that was put in front of me and enjoyed it.


* I'm talking about prevention rather than cure here. I acknowledge that many people have had great success losing fat using low-carbohydrate diets, including two gentlemen I met on Thursday.

Cerner - Fuqua School of Business 'Corporate Ethics 101' Paper and Website Disappear

On April 16 at "Healthcare IT Corporate Ethics 101: A Strategy for Cerner Corporation to Address the HIT Stimulus Plan" I wrote about a Duke Fuqua School of Business paper (apparently authored by a Cerner official) promoting a business strategy of regulatory manipulation to restrain the free market for HIT products.

The paper, and the Fuqua School of Business web page "Past Papers" on which the paper was promoted, have both disappeared as of this April 18 writing.

I have posted an image of the "Past Papers" page and updated my link to an archived copy of the paper, but the scrubbing of the Fuqua site and removal of the paper is interesting.

-- SS

Addendum Apr. 19 -

A former HIMSS staffer related to me that I am likely blacklisted from the HIT vendor industry as a result of my writings on health IT on this site and at my academic site dating to 1999, via verbal exchanges and even in writing among HIT organizations. It could explain why my CV's been uniformly ignored by that industry since the early 2000's.

If so, so be it. Who else might be on that blacklist, I wonder?

Also, didn't Richard Nixon get into a bit of trouble for maintaining such a list after it was discovered?

Health Information Technology Basics From Calif. Nurses Association and National Nurses Organizing Committee

I have never before seen a document like the one entitled "Health Information Technology Basics", by the Institute for Health & Socio-Economic Policy, California Nurses Association and the National Nurses Organizing Committee. It is available at this link (PDF).

It is long but contains rather interesting views on the issue of health IT, management and clinicians (nurses).

I find the following passages of particular interest as they reflect views we express on this blog, and attack the notion of cybernetic miracles being wrought:

Skill is the ability, drawn from education and experience, to do something expertly. It can also be defined as the effective exercise of professional judgment in non-routine situations.

Following prescribed rules, as a machine would, makes an employee competent to perform tasks, but it doesn’t make the employee skilled. They can do their job as long as there are no surprises. But when something unexpected happens, the rules break down, and caring for patients means facing the unexpected every day. Only skilled health professionals can cope with the unexpected. To know what to do, they have to rely on their own judgment. The exercise of judgment is the essence of skill.

... Much health information technology is skill-degrading. As the work of health professionals becomes increasingly automated, they lose the ability to do their jobs without HIT. To make matters worse, they’re expected to keep pace with machines. They serve the machines rather than doing the more gratifying work of patient care, and ultimately they’re compensated less well.

And this:

Displacement [pf people by machines] is hard to spot because it’s unlikely to appear as a one-to one correspondence; that is, you probably won’t find a robot sitting in your colleague’s chair tomorrow. It’s more likely to happen piecemeal, over an extended period, and through attrition.

• The job of patient care will be redefined, privileging technical over clinical skills.
• The hospital will begin to hire more HIT specialists and fewer RNs.
• Functions performed in the past by health professionals will be fragmented and reallocated between machines and less-skilled employees.
• Increased technical efficiency will enable the hospital or HMO to expand without expanding its workforce.

And this:

Use of any hospital technology must be consistent with safe, therapeutic, and effective patient care. Health information technology is a complete unknown in this regard. It’s an enormous social experiment designed by computer scientists and implemented by hospital administrators. HIT hasn’t grown organically from the needs of patients but has been imported from other industries. Known as enterprise resource planning, it’s adapted from similar technology designed to manage business operations on a massive scale and already being used to run the world’s largest corporations.

Caring for patients isn’t business. It requires compassion, judgment, and advocacy. Because RNs have the moral right and legal duty to advocate for patients, they have to be able to override the automated decision-making of HIT designed to serve business interests.

RNs have to work collectively to control health information technology rather than trying to fix it. It’s important to recognize that tinkering can’t fix HIT because its primary purpose is to mechanize, or routinize, patient care. It’s designed to quantify the unquantifiable, to replace the patient with an imaginary statistical norm. High-quality healthcare can’t be mechanized because it depends on people—on patients and caregivers—and people are infinitely more complex and capable than computers can ever be.

Amen to that.

Read the entire document for a union-oriented view of health IT. It contains many truisms regarding HIT irrational exuberance and the control issues of the healthcare management class.

-- SS