Effect Measure

As I write this the story is still hazy [see Addendum] but it sounds like the kind of colossal screw-up we had four years ago when the American College of Pathology sent a pandemic flu strain (H2N2) to thousands of clinical and hospital laboratories as part of routine competency testing (see here, here, here). That was inattention by CDC, whose Director was mesmerized by the bioterrorism phantom and couldn’t see beyond them. This time it’s a vaccine maker and the cock-up sounds pretty horrendous, although it is hard to figure out exactly what has happened given the incomplete descriptions and lack of information from the parties involved:

Baxter International Inc. in Austria unintentionally contaminated samples with the bird flu virus that were used in laboratories in three neighboring countries, raising concern about the potential spread of the deadly disease.

The contamination was discovered when ferrets at a laboratory in the Czech Republic died after being inoculated with vaccine made from the samples early this month. The material came from Deerfield, Illinois-based Baxter, which reported the incident to the Austrian Ministry of Health, Sigrid Rosenberger, a ministry spokeswoman, said today in a telephone interview.

“This was infected with a bird flu virus,” Rosenberger said. “There were some people from the company who handled it.”

The material was intended for use in laboratories, and none of the lab workers have fallen ill. The incident is drawing scrutiny over the safety of research using the H5N1 bird flu strain that’s killed more than three-fifths of the people known to have caught the bug worldwide. Some scientists say the 1977 Russian flu, the most recent global outbreak, began when a virus escaped from a laboratory.

The virus material was supposed to contain a seasonal flu virus and was contaminated after “human error,” said Christopher Bona, a spokesman for Baxter, in a telephone interview. (Michelle Fay Cortez and Jason Gale, Bloomberg)

On first reading this took my breath away because it sounded like a seasonal flu vaccine had become contaminated with H5N1. On second (and third) reading I am not sure what actually did happen and to whom. Here’s what I am unsure about:

  • What was contaminated? The Bloomberg story refers to “samples,” but samples of what?
  • Ferrets succumbed after failing ill after being “inoculated” with vaccine made from the samples. Does this mean it was a live virus vaccine? (inoculation usually means something living; if it were a vaccine without live materials you would ordinarily say “vaccinated” but people don’t always use words precisely).
  • The contaminated material was “for use in laboratories.” What does this mean? It was raw material in a lab that was then made into something else for use outside the lab (like a vaccine)?
  • The contaminated material was supposed to have seasonal flu virus in it, not bird flu virus. It sounds like it had both. (“The company was “supposed to get non-infected testing vaccine, which was by mistake of the supplier contaminated with the H5N1 virus”). That’s a recipe for reassortment between a human and a bird virus. Not the dish I’d like to see served up.
  • Did this happen with a vaccine in clinical trials?
  • We are told that no lab worker has fallen ill. How were they exposed?
  • Labs have been “sanitized.” What exactly does this mean? How was the lab contaminated?

Maybe this isn’t the mess it sounds like. It would be nice to have more information from European health authorities. US CDC is apparently not playing any role, which suggests no US seasonal vaccines are involved. But the source of the contaminated sample was a US company, so inquiry from some US authorities seems appropriate.

That’s not happening as far as we are told. Why not? Lots of questions. Few answers.

Addendum: After drafting this post which was based on published reports, I saw Helen Branswell’s story (via crof’s blog). It doesn’t answer all the questions, but it is characteristically excellent reporting. Rather than summarize the wealth of additional details, go read Branswell’s story. Still, many details are still unclear and Baxter is claiming confidential business information. This seems like something CDC might well want to investigate. Just my opinion.

Comments

  1. #1 Jhony Jay
    February 26, 2009

    The incident is drawing scrutiny over the safety of research using the H5N1 bird flu strain that’s killed more than three-fifths of the people known to have caught the bug worldwide. Some scientists say the 1977 Russian flu, the most recent global outbreak, began when a virus escaped from a laboratory.

  2. #2 M
    February 26, 2009

    Baxter sends out supposedly H3N2 to a vaccine testing lab as a control virus in their challenge studies. They put that in Ferrets and oops, the ferrets die which shouldnt die from H3N2. Turns out the clean H3N2 samples were contaminated with H5N1, which kills ferrets.

    What are the chances that the largest Vaccine maker in the world just spread H5N1 around the world on purpose so that a few lab geeks would get infected and then their newly licenced H5N1 vaccine would have to be bought by ever country to protect themselves?

    Hmmmm

  3. #3 FMA
    February 26, 2009

    Let me fly by and drop a link to a German language news piece from Vienna approx two weeks before the Czech incident:

    http://www.ots.at/presseaussendung.php?schluessel=OTS_20090211_OTS0073

    Coincidence?

  4. #4 Steph
    February 26, 2009

    I don’t know German, so I dropped the text from that link into a free translator:

    Vienna (OTS) – at the past Monday, Otto-Wagner-hospitals were treated in the Viennese 18 colleagues of an
    external business ambulatory because first of all excluded become not could, that they had come in the frame
    of its work with a bird flu pathogen in contact. With none of the comprehensive tests, an infection was
    assessed. ****

    In addition the patients were treated immediately with a flu provision. “Neither for the patients and
    patients yet for persons, who were with them in contact, a threat existed. Obviously we informed however all
    responsible authorities”, explained de Vienna in Susanne Drapalik of the general management of the hospitals
    of the city. (End) cl

    Query reference:

    PID city hall correspondence: http://www.wien.at/vtx/vtx-rk-xlink/ Viennese sick institute association/press Conny
    Lindner telephone: 01,404 09-70054 e-mails: cornelia.lindner@wienkav.at

    *** OTS original text PRESSEAUSSENDUNG UNDER EXCLUSIVELYER RESPONSIBILITY OF IN REGARD TO CONTENT THE from
    transmitter – http://WWW.OTS.AT ***

  5. #5 Jody Lanard M.D.
    February 26, 2009

    The notion that Baxter is not reporting out all the details due to propietary production secrecy needs is beyond outrageous.

    Sending H5N1 contaminated virus samples to three countries should qualify as a public health incident of global concern, and the International Health Regulations should kick in.

    Delaying public reporting of this potential catastrophe for weeks is unforgiveable and reprehensible.

    Baxter should be forced to publicly explain every step of its investigation and findings, so that other companies, universities, and government labs can check their security processes against what went wrong at Baxter.

    Let me translate what Baxter said: “We care much more about profit than about global public health. We’d rather not reveal how we might have launched the next pandemic than tell you anything about how we (mis)handled H5N1.”

    Who provided the H5N1 sample to Baxter? Ultimately, probably a WHO collaborating lab. WHO should immediately ban Baxter from receiving any further samples of any sort from any WHO collaborating lab — until Baxter offers a fully candid, transparent, honest report about what happened, and until WHO, the governments, and the publics of the effected countries have no further questions or concerns about Baxter’s competence and candor.

  6. #6 revere
    February 26, 2009

    Stephanie: Here’s a (very) rough translation:

    Last Monday 18 female employees of a foreign? company were treated on an outpatient basis because of suspicion they may be been exposed to the bird flu virus at work. Extensive testing did not reveal evidence of infection.

    The female patients were treated immediately with a drug to prevent influenza [presumably Tamiflu]. “None of the employees or any person in contact with them were in any danger,” said Dr. Susanne Drapalik of the General Administration of Hospitals for Vienna. “Of course we notified the official agencies.”

    Maybe some fluent German speakers can correct any errors, but I think that’s the gist. This news story is dated February 11, 2009, so the event was on February 9 (a Monday).

  7. #7 JJackson
    February 26, 2009

    The research work being performed by Biotest was called to a halt on the 6th (Friday), after the ferrets started dying.

  8. #8 JJackson
    February 26, 2009

    What I should have made clear is that Biotest is the Czech lab that was contracted by to Avir Green Hills which in turn was contracted by Baxter (Austria). It is a little over 200 miles, as the crow flies, from Biotests labs in Konárovice to Vienna.

  9. #9 daedalus2u
    February 26, 2009

    Correct me if I am wrong, but it is my understanding that H5N1 can’t be grown in chicken embryos (the usual substrate for flu virus growth) because it kills them too quickly.

    So how did they grow the virus they sent out for testing? Mammalian cell culture?

    I agree with Revere, the danger is in the potential for recombination when H5N1 is co-grown with other flu virus, which they already seem to have done in this case.

    The quote in the Bloomberg article was a little disingenuous, “even if it were let out of the lab, would be only lethal for birds in its present state,” um, then why did the ferrets die? Are ferrets a new kind of bird?

    Or are they saying that H5N1 did recombine into something that was lethal for mammals and it is the recombined form that killed the ferrets?

  10. #10 JJackson
    February 26, 2009

    daedalus2u
    If you want to grow HPAI H5N1 in eggs you do a bit of engineering first so the HA & NA sites still produce good antibodies but you lose the virulence.
    As to the quote Baxter are in full spin mode and releasing no information about how the contamination occured. Keeping quiet has been effective form the 6th for a little over 2 weeks but the first stories appeared in the Czech press on the 17th (hat tip Dutchy @ Flutrackers) but was not picked up by MSM until the Bloomberg article.
    I don’t think Baxter’s plan was going to work as the regulatory authorities in four european countries (and possibly the US if “The material came from Deerfield, Illinois” is correct and there is question mark about that). I hope Jody will come back after this is all over and give us a post game analysis on Baxter’s communication stratagy.

  11. #11 franc
    February 26, 2009

    …is this another coincidence or is this a part of explanation?

    http://www.european-hospital.com/topics/article/1182.html

  12. #12 revere
    February 26, 2009

    franc: I’m with you. I’ll bet this is part of the explanation. Right now, though, Baxter is not being very forthcoming. European authorities should force their hand, assuming they want to. Maybe the don’t.

  13. #13 Brendan
    February 26, 2009

    daedalus2u: ordinarily, you’re right (about growing h5n1 in eggs), which is why you need to use reverse genetics (as jjackson said, taking the internal genes from an h1n1 strain (“pr8″) and mixing it with the h5 and n1). but, baxter uses mammalian tissue culture cells in their preparation, which allows them to grow fully virulent h5n1 without doing any modifications.

  14. #14 Brendan
    February 26, 2009

    jjackson: my understanding from the canadian article linked by revere is that avir green hills contracted the h3n2 from baxter, not the other way around. (from the article: “The facility had been contracted by Avir Green Hills to make what Baxter refers to as “experimental virus material” based on human H3N2 viruses.”)

    avir green hills is working on a seasonal and pandemic vaccine, and i believe both are live-attenuated. i find it really weird that baxter, which is a vaccine company, denies that what they shipped avir green hills, et al. was a vaccine. instead, they said it was a “liquid virus product.” i have no idea what this could be.

  15. #15 pft
    February 27, 2009

    Funny how Panasonic last month advised all employees working abroad to send their families home to Japan, out of fears for a pandemic flu breaking out next fall.

    I will spare you my conspiracy theory.

  16. #16 pft
    February 27, 2009

    I meant all Japanese employees working abroad

  17. #17 Brendan
    February 27, 2009

    pft: just to clarify, panasonic didn’t repatriate the families of all employees working abroad, just those who work in areas with questionable public health / medical infrastructure (e.g., south america, eastern europe).

  18. #18 JJackson
    February 27, 2009

    Brendan
    I do not think the contaminated sample came from the US (as in the Baxter article). I think it was made at “Baxter['s] pilot plant in Orth, Austria can produce smaller quantities of candidate vaccines for clinical trials using Vero cell technology” (the bit in quotes is from a Baxter doc on their Vero cell based vaccine technology. They have a production facility “The facility, located in Bohumil, Czech Republic, is engineered for BioSafety Level 3
    production, and can produce up to 100 million doses of pandemic vaccine annually,depending on vaccine specification, dosage and yields of strains”).
    As explained by a Baxter spokesman the ‘error’ occurred in Baxter Austria and they had subcontracted some research to AGH (Austria). AGH subcontracted work on the ‘experimental Vaccine’ to Biotest, and others, and forwarded it on the 30th Jan. (Friday). Biotest began trials the following week by the end of which they had dead ferrets and an obvious problem. On the following Monday (11th) people were being given Tamiflu in Vienna so someone knew or suspected H5N1 exposure. First press involvement was local to Biotest in the Czech republic at the end of that week (dated 17th) and spread from their. That is the chronology as I understand it and all players thought they were dealing with H3N2 and used appropriate protocols.
    None of which is very interesting, apart from a PR point of view. What we want to know is the nature of the H3N2 entity. Was it live or a vaccine, what is the nature of the H5N1 (dead ferrets and prophylactic Tamiflu so assumed live), how the two ever managed to be in the same place at the same time to allow contamination and having occurred how it then got out of the BSL3 facility and into civi street. None of which Baxter seem willing to discuss.

  19. #19 JJackson
    February 27, 2009

    P.S.
    The H5N1 was A/Vietnam/1203/2004 which is being used by Baxter in phase 3 clinical trials in Austria (NCT00462215)

  20. #20 Steph
    February 27, 2009

    Thank you, Revere! Curiouser and curiouser – so does anyone know if that “liquid virus product” went out to any other labs? (say in other countries)

  21. #22 Andreas
    March 7, 2009

    @ Stephanies translation:
    18 female employees is wrong, right is: 18 employees male or female

    foreign? company is wrong, right is: a company not belonging to the Hospital

    The female patients were treated is wrong, see above

    hope that helps

    Andreas (better in german than english)

  22. #23 george
    March 8, 2009

    WE THE PEOPLE ARE BEING ROBBED AND MURDERED BY A GLOBAL ELITE…WHAT ARE WE GOING TO DO ABOUT IT?
    CAN ANYONE SAY “REVOLUTION”?

  23. #24 revere
    March 8, 2009

    OK, folks. Go out and buy some Reynolds Wrap.

  24. #25 paiwan
    March 8, 2009

    LOL.

    Be careful of the sugar level- type2.

  25. #26 Lea
    March 8, 2009

    Wait a minute dear hearts, revere-be, there are a great number of people who believe this to be true, and that number truly is growing.
    Don’t make fun of what you don’t understand. Cover your bases and research everything that is going on.

  26. #27 victoria
    March 9, 2009

    Like yeh! You big bully!

  27. #28 paiwan
    March 9, 2009

    CAN ANYONE SAY “REVOLUTION”?

    Except using machine gun, George, if there is something in your mind just tell us; what kind of revolution do you think that will help?

  28. #29 analyitcal
    October 31, 2009

    The pharmaceutical companies have to follow the GMP (good manufacture practice) regulations. Every drug products have to ensure their products are free from the contamination sources. They have to use their own testing laboratory or the independent to test their products. What’s happen to the quality control department of Baxter?

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