A while back, we posted frequently about the sudden toxicity of what used to be an apparently well understood drug. A summary of the story to date is below (in smaller type.):

- 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.
- Then, 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.”
- The parties involved, including the US Congress, the US Food and Drug Administration, its Chinese counterpart, Baxter International, Scientific Protein Laboratories, blamed each other for the problems (see post here).

Since the beginning of May, the story has become surprisingly anechoic. Just recently, however, a brief, grim reminder appeared (e.g., by Bloomberg News, via the Boston Globe):

The blood thinner heparin has been linked to 149 US deaths in people who had allergic reactions after taking it, US regulators said.

The new tally, posted yesterday on the Food and Drug Administration’s website, expands the toll of people who took the drug and suffered allergic reactions. The agency said in April it knew of 81 people who died after suffering allergic reactions from the drug, made from pig intestines.

But since early May, no more seems to be known about where the contaminant was introduced in the supply chain, who introduced it, or whether faulty oversight on the part of Baxter International or Scientific Protein Laboratories allowed the contamination to go undetected.

The mounting death toll from contaminated heparin suggests that the outsourcing of core functions of health care organizations may need to be rethought.

Thus, the recent discussion on the Managed Care Matters Blog, by Joe Paduda about the perils of brain-dead outsourcing seems particularly relevant. He first noted:

In the old days, companies tried to control as much of their raw materials - and the refining and transportation of those raw materials - as possible. In addition to auto plants Ford owned iron mines, steel mills, glass factories, rubber plantations, ships, and railroad cars. Nowadays Ford outsources some of its vehicles’ key components (engines, transmissions, steering linkages) to other companies, concentrating on designing, assembling and marketing instead.

Over the last couple of decades, manufacturers found themselves increasingly relying on other companies for critical processes and components - if all worked well, profits zoomed, and if not, heads rolled.

But often this sort of outsourcing often breaks down

and when it does disaster often ensues

He had plenty of examples,

Sony buys LCD panels not on clarity and brightness but on cost, thinking hey, they are cheap so more folks can afford them - don’t worry if the picture is lousy and colors muddy - in fact don’t even look at the picture before you select a vendor.

Paduda cited the example of Compaq, once one of the major US makers of personal computers (and the first maker of a practical “lugable” computer.) Based on an interview with “disruptive technology” guru, Clayton Christensen, Paduda summarized how Compaq first outsourced some of the circuit boards in the computer, and saved money in the process. Then they outsourced the mother board, the main computer circuit board. Then they outsourced the design of the computer. As Christensen said, Compaq managers agreed, “our core competency is really our brand. We can fire all the engineers....” The result was, “the supplier in the Third World starts to eat their way up inside the customer, and every step forward they take progressively trivializes the remaining value Compaq adds, until in the end they’re providing almost no value and the company vaporizes.”

The key lesson here, which was not stated by Paduda or Christensen, is confusion about what an organization’s core really is. The rationale for a company to outsource is that an outside organization may be able to provide non-core functions at a lower cost. Real problems arise, however, when managers seem to progressively decide that less and less of the organization’s functions are core.

It may be that many managers seem to think that what they do is the only real core part of the organization, that is, that they, the managers, are the only indispensable part of the organization. It may be that many managers, trained as super-generalists, believe only they have the brilliance to manage any organization, even if they do not understand the context in which it operates, or the technical or scientific rationale of its products. Scientists, engineers, professionals, assembly line workers, service specialists to such managers are all superfluous. Of course, it may actually be harder to find specialized technical workers or professionals, or to set up complex manufacturing processes, than to find a few more self-proclaimed genius MBAs.

In my humble opinion, this kind of thinking has infected many health care managers. It may have contributed to the death of 149 people from out-sourced, contaminated heparin. More disasters are likely to ensue, and will keep happening until we reaffirm what the core of health care organizations really is.

It is dedicated health care professionals sworn to put patients’ interests first. It is scientists who mean to discover the truth about biology and disease. It is the complex, often highly technical infrastructure that allows good care to happen for particular patients at the time it is needed, and the particularly qualified people who staff that infrastructure.

It is not managers who do not understand health care, medicine, or biology. It is not marketing. It is not accounting. It is not legal services. Maybe we have the outsourcing in health care all backwards.

[Source : Health Care Renewal]

It is time to update the story of the contaminated heparin. A summary of the story to date is below (in smaller type.):

- 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.”

We most recently commented on this case here. There have been some major developments since.

• The US Food and Drug Administration (FDA) inspected the Changzhou SPL plant, finding “significant deviations” from good manufacturing practices.(1) The FDA warning letter asserted “your firm lacked an adequate evaluation of the effectiveness of critical processing steps designed to remove impurities, and critical process parameters were not well defined or controlled.” Also, “you received lots of material from an unacceptable workshop vendor that were used in your API [active pharmaceutical ingredient].” In addition, “Your system for evaluating suppliers of crude heparin material is ineffective to ensure that materials are acceptable for use.” Finally, “Equipment used to manufacture heparin sodium USP is unsuitable for its intended use.”(2)
• Scientific Protein Laboratories (SPL) provided a statement that “the contaminant found in certain lots of finished heparin product was not introduced in the manufacturing process at Changzhou SPL or SPL.” Furthermore, “it is now clear that the suspect contaminant was introduced earlier in the supply chain in China and was widespread throughout the unrelated Chinese supply chain of many companies.”(1)
• Baxter International claimed it had inspected the Changzhou SPL plant, per the Wall Street Journal, but a senior congressional investigator said, “Baxter conducted one audit of the Chinese plant, in September 2007, and concluded the plant was acceptable.”(3) Furthermore, the New York Times reported that “the company sent one person who spent one day in the plant, Mr. Nelson said. Five months later, the F.D.A. discovered myriad problems, he said. ‘It really is impossible for a plant to have fallen that far out of compliance in five months,’ Mr. Nelson said.”(4)
• The FDA seemed to concur that the contamination began in China before the heparin was supplied to Changzhou SPL. Per the Washington Post, “new evidence that links hundreds of serious adverse reactions and scores of deaths among patients given the blood thinner heparin to a man-made contaminant introduced during production in China. Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, said that the contaminant has been traced to 12 different Chinese companies and has been found in heparin batches shipped to 11 nations, all of it from China.”(5)
• However, Chinese officials disputed the conclusion that the contamination came from China, and instead suggested it occurred in SPL’s plant in the US. Per the Washington Post, “Jin [Shaohong, an official with the Chinese National Institute for the Control of Pharmaceutical and Biological Products] said the Chinese government was conducting its own investigation of the heparin issue, which would include a visit today to Baxter’s New Jersey processing plant, where officials hoped to collect additional samples of the tainted drug. He said the allergic reactions could have been created by impurities introduced when the imported raw heparin was refined by Scientific Protein Laboratories (SPL) of Wisconsin and then prepared for distribution in New Jersey.”(5)
• Per Forbes, The CEO of Baxter International, Robert Parkinson, “said at a congressional hearing that it wasn’t responsible for contaminated batches of Heparin, an anticoagulant used mostly in hospitals, and that it may have been a deliberate contamination.” In particular, he said, “we’re alarmed that one of our products was used, in what appears to have been a deliberate scheme, to adulterate a life-saving medication, and that people have suffered as a result.”(6)
• Per the Chicago Tribune, the CEO of Scientific Protein Laboratories said “Chinese authorities have blocked his company’s efforts to inspect suppliers that might have introduced foreign material into the company’s heparin.’We started an inspection, but at a certain time the Chinese authorities took over a very significant inspection, and felt we should not be interfering with an inspection by the Chinese authorities,’…”(7)
• Congresspeople blamed the FDA. According to the Wall Street Journal, Rep. John Dingell (Democrat - Michigan) said, “Our citizens can no longer trust their food, drugs, or medical devices are safe when the FDA says they are.”(3)

So, everyone is to blame, and practically every organization involved blames another one.

Congress blames the FDA, but congress is responsible for funding the FDA insufficiently for it to inspect all the foreign plants that now supply active pharmaceutical ingredients to the US, and for funding the FDA with “user fees” that may have lead many in the FDA to view the drug companies, rather than the American public, as their clients.

The FDA blames Changzhou SPL and its suppliers, but the FDA is responsible for the safety and purity of US drugs, and therefore has responsibility for the entire supply chain responsible for drugs prescribed in the US.

Baxter International blames nefarious contaminators, but Baxter is responsible for making sure that the drugs it sells are pure and safe.

Scientific Protein Laboratories blames the contaminators, and the Chinese government for blocking attempts to inspect its suppliers, but SPL is responsible for making sure the active pharmaceutical ingredient it sells to pharmaceutical companies are pure and safe.

The Chinese government blames the American companies, but the Chinese government ought to be responsible for products exported from its country.

I could not find any evidence that any leader of any involved organization assumed any responsibility for anything that went wrong during this fiasco. It reminded me of stories that when adolescents are caught by the US police, they often blame their offense on “some dude,” otherwise not identified.

This case is an amazing example of global health care dysfunction. Each organization listed above, of course, bears some but not all responsibility. Although the leaders of these organizations are supposedly chosen because of their ability and willingness to take responsibility (and the leaders of the US corporations are paid very handsomely supposedly for taking such responsibility), all they have done so far is try to avoid responsibility, and blame “some dude” for the problems.

And this goes on in an era where physicians are constantly badgered about how they must be responsible, be accountable, and be paid for their “performance.”

When we get some adult leadership of health care organizations who are willing to take responsibility and be accountable for their organizations’ actions, maybe we will have a more functional health care system. Such leaders might find out that bearing responsibility and being accountable would involve putting patients before profits, or ego. (I also bet adult leaders with more secure egos might be willing to work for less than the millions a year now required by the “imperial CEOs” of US health care corporations.)

Finally, as a reminder of the consequences of the current dysfunction, the death toll for the case of the contaminated heparin is now estimated to be 81.(4)

References

1. Japsen B. FDA: heparin supplier’s Chinese factory ‘unsuitable.’ Chicago Tribune, April 21, 2008. Link here.
2. FDA. Letter to Dr Yan Wang, General Manager, Changhzhou SPL Company, Ltd. April 21, 2008. Link here.
3. Favole JA, Boles C. Lawmakers seek heparin answers from FDA and Baxter officials. Wall Street Journal, April 29, 2008. Link here.
4. Harris G. Heparin contamination may have been deliberate, F.D.A. says. New York Times, April 30, 2008. Link here.
5. Kaufman M. New data link heparin deaths to Chinese batches, FDA says. Washington Post, April 22, 2008. Link here.
6. LaMotta L. Heparin: the plot thickens. Forbes, April 29, 2008. Link here.
7. Japsen B, Greising D. Baxter CEO tells congress heparin tampering was deliberate. Chicago Tribune, April 29, 2008. Link here.

[Source : Health Care Renewal]

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.

[Source : Health Care Renewal]

We have posted several times, most 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 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. 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.)

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.”

By the end of this week, it became clear that the counterfeit ingredient was added to the heparin in China. Per Bloomberg,

The contamination was present in the powdered raw heparin purchased by Scientific Protein’s plant in China, said Robert Rhoades, a pharmaceutical consultant with Becker & Associates in Washington, speaking for Scientific Protein. The company was unaware of the contamination at the time because it wasn’t detected in tests Scientific Protein conducted on the powder provided by suppliers, he said.

Scientific Protein purchased raw heparin from consolidators and refined it further before sending it to Baxter, which uses the ingredient to make the finished drug, Rhoades said. The consolidators obtained the ingredients from workshops in China, he said.

The contaminant ‘was very likely introduced at the workshop or consolidator level,’ Norbert Riedel, Baxter’s corporate vice president and chief scientific officer, has said.

Nonetheless, a number of experts suggested that there was reason not be complacent about drugs made in China. A Washington Post article noted that it was well known that Chinese manufacturers were liable to supply dodgy drugs,

Although the contaminated heparin is the largest and highest-profile instance of tainted prescription drugs made in China, it is not the first. In the late 1990s, a spike in deaths associated with the intravenous antibiotic gentamicin was linked to China-based Long March Pharmaceuticals. Although no definitive link was ever established, tests by German researchers later found a wide range in quality and effectiveness in what were supposed to be uniform dosages of the drug, leading them to write that ‘it was assumed’ the deaths ‘were related to faulty manufacture.’

The Post quoted former US Food and Drug Administration (FDA) official William Hubbard,

The history of some of these developing countries in terms of substituting or counterfeiting concerns is a long and well-documented one….

USA Today quoted former FDA Commissioner David Kessler saying that

the news shouldn’t come as a surprise: China is ‘as close to an unregulated environment as you can get.’ In fact, it’s a lot like the USA was in 1906, he says —’that’s why we developed an FDA.’

Furthermore, one expert argued that Baxter International was ultimately responsible for the drug that it sold, per the Chicago Tribune,

The presence of a foreign ingredient raises new questions about Baxter’s oversight because a lack of record-keeping at the China plant makes it more difficult for Baxter and government inspectors to trace the origin of the raw material for Baxter’s product.

‘Where are the controls here? What is the process here?’ asked Carl Nielsen, who was the FDA’s director of import operations and policy before leaving the agency to form a consulting firm in 2005.

‘Ultimately, Baxter is the most responsible’ for monitoring the quality of products that move through the company’s pipeline, Nielsen said.

Yet Baxter International executives have not exactly been jumping forward to claim responsibility. In a letter, again to the Chicago Tribune, Peter J Arduini, President, Medication Delivery, for Baxter International seemed to be deflecting responsibility towards Scientific Protein Laboratories and the FDA, while asserting Baxter did all it could do.

Regarding the issue of active pharmaceutical ingredient that originated in China, Baxter’s API supplier for heparin is in fact a Wisconsin-based company, Scientific Protein Laboratories, with whom Baxter and its predecessor in this business has worked for more than 30 years. SPL had been procuring heparin raw material from China for more than 10 years and opened a location in Changzhou, China, in 2004. Baxter worked with the U.S. Food and Drug Administration to obtain the appropriate approvals to work with this facility. For the API we receive from SPL, and for the API we receive from all our suppliers, Baxter performs quality testing of all incoming materials above and beyond what’s required, to ensure that incoming API is what our suppliers claim it to be. Unfortunately, as the FDA has said, the problematic heparin API could not have been detected by the testing required of and done by any heparin manufacturer.

Previously Baxter International’s CEO, Robert L Parkinson Jr, had dodged responsibility for the supply chain that provided the heparin to Scientific Protein Research’s Changzhou facility, as we posted here, and as originally reported in the Chicago Tribune,

Baxter International Inc. does not monitor its supply chain to the extent that it would know that a supplier in China was never inspected before it began shipment of the blood-thinning drug heparin, which is linked to more than 300 illnesses in the U.S., the company’s chief executive said Wednesday.

Baxter contracted with a Wisconsin supplier, Scientific Protein Laboratories, and not with that company’s Chinese affiliate, Baxter CEO Robert Parkinson said Wednesday in his first interview since the heparin problems surfaced.

‘It’s not unusual for us not to know that the FDA hasn’t inspected a supplier to a supplier,’ Parkinson said.

Yet if Baxter International is not responsible for the production of drugs that carry its name, who is? If Baxter International’s executives are not responsible for how the drugs it sells are manufactured, who should be?

In an ironic juxtaposition, a small and little noticed news item last week declared that Robert Parkinson received $16,600,000 in compensation in 2007, a 30.5% increase from 2006. In fact, the company’s 2008 proxy statement suggests even greater total compensation in 2007, $17,580,718. And Mr Arduini’s 2007 compensation was reported to be $2,438,642.

The usual justification for compensation at this level is the brilliance of and great responsibilities borne by the executives who receive it. But, if Baxter International’s executives will not take responsibility for their products and how they are made, what again is the justification for paying them the big bucks?

So the case of the contaminated heparin becomes another reason to question the imperial nature of the current leadership of health care organizations.

[Source : Health Care Renewal]

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.

[Source : Health Care Renewal]