Disaster/Pandemic preparedness - page 15

I was looking the the other Disaster/Pandemic thread that Florida1 started. She mentioned that after the hurricanes, that they had problems getting basic supplies and food stores were often closed... Read More

  1. by   indigo girl
    THE PANDEMIC VACCINE PUZZLE

    Part 2: Vaccine production capacity falls far short

    Maryn McKenna Contributing Writer

    "Editor's note: This is the second in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 1 described how flu research has been a relatively low priority until very recently, which has left many important scientific questions unanswered."

    http://www.cidrap.umn.edu/cidrap/con...07panvax2.html

    Quote from http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2607panvax2.html


    ...achieving a widely deployable pandemic vaccine is currently out of reach... The world lacks the manufacturing capacity to make enough vaccine to matter.


    A vaccine-industry scenario, described in August in the journal BioPharm International, goes out 6 months...adding up to a vaccine product that would arrive roughly in time for the pandemic's second wave but long after the first patients had recovered or died


    But the more difficult obstacle is not the time needed to produce vaccine...but the amount of vaccine needed.


    ... a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. So absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants


    The WHO analysis hides a number of highly optimistic assumptions, including zero glitches in production and 100% cooperation by regulators.... It is...likely that vaccine would never leave the countries where it is produced.


    The WHO action plan avers that manufacturers will significantly expand production capacity by 2012, largely because demand for seasonal flu vaccine will rise--but it offers no evidence that demand can be stimulated to levels that will persuade manufacturers to invest


    The WHO plan asks countries that do not now use seasonal flu vaccine to launch new seasonal vaccination campaigns as a way of stimulating demand. It also asks countries with existing vaccination programs to increase vaccine use, so that 75% of those for whom vaccination is recommended are taking the shot


    Creating enough vaccine-manufacturing capacity to protect the world's population is not cheap. The price tag is likely to be at least $2 billion and could rise to $9 billion... Experts within the vaccine industry say that expecting manufacturers to make the investment asks companies to spend against their own best interest.


    While vaccine manufacturers are likely grateful for the HHS funding, others in the industry say the investment is incomplete--because it does nothing to expand capacity for critical downstream tasks such as bottling and administering completed vaccine.


    "You have to think about every part of the components," Lysfjord said. "The machines, the plants, the chemicals; the stopper, the glass, the aluminum overcast for the top of the vial; the labels. You're not aware of how well-connected the system is until it breaks, and it is going to break big-time."
  2. by   sirI
    indio girl.....

    ...achieving a widely deployable pandemic vaccine is currently out of reach... the world lacks the manufacturing capacity to make enough vaccine to matter.
    .....how many manufacturer's are there now worldwide? i know the u.s. has at least 5, is that correct? (do they supply the world as well??)


    ... a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. so absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants
    i'm sure this information is not common knowledge. thank you for the continued updates.
    Last edit by sirI on Oct 27, '07
  3. by   mcmike55
    All real good suggestions, good posting as well. With the fires in California, a timely topic as well.
    I have a suggestion for all you good folks, take CERT training.
    CERT, Community Emergency Response Team training is done through the EMA in your area, and teaches basic medical operations, fire suppression, disaster psychology, and search and rescue.
    The idea is to teach you how to first, take care of yourself and your family in the time of an emergency, then if possible, how to go out and help your neighbors.
    I teach the classes here in SouthEast Ohio, and really think they are great, not only for nurses, but fire, EMS, or any citizen.
    Check out your local EMA, or go on line and search CERT or try the Home Land Security website.

    Mike
  4. by   indigo girl
    Quote from sirI

    ....How many manufacturer's are there now worldwide? I know the U.S. has at least 5, is that correct? (do they supply the world as well??)
    Thanks, sirI, and thanks to CIDRAP for this series.

    Who makes the flu vax that you are using?

    If we are talking strictly flu vax, all I am hearing about is Sanofi Pasteur in
    Swiftwater, Pa, and I think that FluMist by Medimmune is out of Gaithersburg, Md(?). I could be wrong about that one, but I think they have a plant in the US.

    Novartis has broken ground for a plant in North Carolina.

    Anyone else know of any flu vax producing plants actually on US soil?

    CIDRAP is correct. The US is at disadvantage in this respect.

    The following have plants outside the US:

    Baxter
    Chiron
    Medimmune + AstraZenica
    Aventis Pasteur
    Acambis
    Wyeth
    (Thanks to Ayerman, andPFI/pixie,JWB,UKbird for this list)
    Last edit by indigo girl on Oct 28, '07
  5. by   indigo girl
    Quote from mcmike55
    All real good suggestions, good posting as well. With the fires in California, a timely topic as well.
    I have a suggestion for all you good folks, take CERT training.
    CERT, Community Emergency Response Team training is done through the EMA in your area, and teaches basic medical operations, fire suppression, disaster psychology, and search and rescue.
    The idea is to teach you how to first, take care of yourself and your family in the time of an emergency, then if possible, how to go out and help your neighbors.
    I teach the classes here in SouthEast Ohio, and really think they are great, not only for nurses, but fire, EMS, or any citizen.
    Check out your local EMA, or go on line and search CERT or try the Home Land Security website.

    Mike
    An excellent suggestion. Thank you.
  6. by   sirI
    Quote from indigo girl
    Thanks, sirI, and thanks to CIDRAP for this series.

    Who makes the flu vax that you are using?

    If we are talking strictly flu vax, all I am hearing about is Sanofi Pasteur in
    Swiftwater, Pa, and I think that FluMist by Medimmune is out of Gaithersburg, Md(?). I could be wrong about that one, but I think they have a plant in the US.

    Novartis has broken ground for a plant in North Carolina.

    Anyone else know of any flu vax producing plants actually on US soil?

    CIDRAP is correct. The US is at disadvantage in this respect.

    The following have plants outside the US:

    Baxter
    Chiron
    Medimmune + AstraZenica
    Aventis Pasteur
    Acambis

    (Thanks to PFI/pixie,JWB,UKbird for this list)

    CSL Ltd out of Australia is providing the U.S. with Afluria (a fast-tracked vax): http://www.medicinenet.com/script/ma...ticlekey=84217 . This makes the 6th manufacturer, but not on U.S. soil.

    We use FluMist (yes, they are out of Maryland). And, Fluzone.
  7. by   AnneZ
    ...achieving a widely deployable pandemic vaccine is currently out of reach... The world lacks the manufacturing capacity to make enough vaccine to matter.
    .....How many manufacturer's are there now worldwide? I know the U.S. has at least 5, is that correct? (do they supply the world as well??)

    ..
    . a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. So absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants
    I'm sure this information is not common knowledge. Thank you for the continued updates.


    Influenza vaccine manufacturers
    http://www.who.int/csr/disease/influ.../en/index.html

    Baxter. Austria
    France. Aventis Pasteur SA
    Italy. Istituto Vaccinogeno Pozzi
    Germany. GlaxoSmithKline
    Germany. Chiron Vaccines
    Italy. Chiron Vaccines
    Japan. Denka Seiken Co. Ltd
    Australia. CSL Limited
    Canada. ID Biomedical
    China. Beijing Tiantan Biological Products
    China. Changchun Changsheng Life Sciences Ltd
    China.Lanzhou Institute of Biological Products
    China. Typharm
    Japan. Chemo-Sero-Therapeutic Research Institute
    Japan. Biken Research Foundation for Microbial Diseases of Osaka University
    Japan. Kitasato Institute
    Korea. Dong Shin Pharmaceutical Co
    Netherlands. Solvay Pharmaceuticals
    Netherlands. Crucell NV
    Romania. Cantacuzino Institute
    Switzerland. Berna Biotech Ltd
    UK. Chiron Vaccines (there are 2)
    US. MedImmune Vaccines Inc
    Last edit by AnneZ on Oct 27, '07
  8. by   indigo girl
    Thanks, AnneZ, and flutrackers for the assistance.

    I really did not know that there were this many vaccine
    manufacturers. Alas, most not on US soil.

    The following information is from monotreme at PFI, and I thank him also
    for his contribution:

    <snip>


    During a pandemic, seasonal flu vaccine plants will be converted to use for pandemic flu vaccine. Since the seasonal flu is trivalent, assuming equal amounts of antigen, flu vaccine supply would be triple current output during a pandemic. However, early H5N1 vaccines required very high levels of antigen to stimulate an immune response. And two immunizations would be needed. This would imply less flu vaccine available during a pandemic. OTOH, adjuvants like MF59 allow less antigen to be used to stimulate immunity, so less might be used.


    http://www.reuters.com/article/gover...27223720070719

    The vaccine arm of Sanofi-Aventis is the only U.S.-based producer of injectable flu vaccine. The plant will produce 150 million doses a year after the new 140,000-square-foot (13,000- square-metre) facility comes on line by 2010.

    FluMist was based in Gaitersburg Maryland when it was made by MedImmune. MedImmune was bought by Astra-Zeneca. It appears to be produced in the UK. I'm not sure how much is actually produced in the US.
    MedImmune says it resolves FDA FluMist plant issues

    http://www.reuters.com/article/healt...26177020070907


    HHS Awards Two Contracts to Expand Domestic Vaccine Manufacturing Capacity for a Potential Influenza Pandemic

    http://www.hhs.gov/news/press/2007pr...20070614a.html

    <snip>
  9. by   indigo girl
    Teaching Kids About Flu Prevention

    As always, thoughtful commentary and useful information from SophiaZoe's
    blog.

    http://birdflujourney.typepad.com/a_...ic-influe.html

    Quote from //birdflujourney.typepad.com/a_journey_through_the_wor/2007/10/pandemic-influe.html

    Two years ago, Geri Rodda wrote the 32-page children's health story "Lyme and in Rhyme" about Lyme disease. Both softcover books were published by Pumpkin Hill Productions, a small company in Hawleyville. MedImmune Inc. in Maryland (producers of FluMist vaccine) provided a grant to publish 1,000 copies of "The Flu and You."

    The new 36-page book, with Crayola-style color pages, wild-haired cartoon characters and rhyming verse, is fun to read and provides a strong message on how to prevent and treat influenza. It is appropriate for children to read alone or for parents and grandparents to read aloud.
    Last edit by indigo girl on Oct 30, '07
  10. by   indigo girl
    The Pandemic Vaccine Puzzle

    Part 3: H5N1 poses major immunologic challenges

    Maryn McKenna Contributing Writer

    "Editor's note: This is the third in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 2 discussed the huge gap between current global vaccine production capacity and the likely demand for vaccine in the event of a pandemic."

    http://www.cidrap.umn.edu/cidrap/con...07panvax3.html

    Quote from //www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2907panvax3.html

    ...antigenic drift and division into clades, or subgroups, has already rendered some early vaccine candidates less potent against circulating strains.

    ...highly pathogenic, it must be handled initially in one of a relatively small number of high-biosecurity laboratories...

    ...requires the use of reverse genetics to create a seed strain that will reproduce in eggs.

    Reverse genetics and the stringent pre-release testing that follows add a minimum of 6 weeks to the vaccine production process

    ...seed strain could be considered a genetically modified organism under European Union rules or a select agent under US law, further restricting the laboratories, personnel, and manufacturers who could work with it from then
    on
    .


    "Most manufacturers report that yields of antigen from reverse genetics-derived H5N1 viruses are 30-40% of the average of seasonal influenza viruses, reducing the quantity of antigen available for vaccine formulation



    ...when candidate vaccines have been produced from them, H5N1 and similar viruses have not done a good job of provoking an immune response.


    ...the best example of H5N1's poor immunogenicity is the 2006 trial that led to the first FDA licensing of an H5N1 vaccine. The trial... achieved acceptable levels of protection only at the highest amounts given, two doses of 90 mcg each, or 12 times the 15-mcg dose that induces immunity in a seasonal vaccine



    Even at that dosage, only 54% or 58% of the subjects (by two different measures) exhibited antibody titers that matched FDA and CHMP regulations, compared with the 70% to 90% usually achieved with seasonal vaccine


    The amount of antigen needed... is so high that the vaccine would stress the manufacturing system if put into broad production...


    ...the high dose--which at 180 mcg total is four times the total seasonal trivalent dose--could provoke an unusual rate of adverse reactions...

    ...the 90-mcg vaccine... will contain the still-controversial preservative thimerosal.


    ...our biggest scientific issue--that we are not sure what the appropriate surrogate for protection is, given the fact we have no ability to challenge [expose humans]...


    ...the FDA-accepted surrogate for immunity in flu-vaccine trials is a hemagglutination-inhibition (HI) antibody assay that returns a post-vaccination titer of more than 1:40 for 70% of those vaccinated ...But that measure is known to be imperfect even for seasonal flu:


    .....Researchers have resorted to using a 1:40 result...


    ...It's important to understand that this choice of a 1:40 endpoint is not validated in any way as an actual assessment of protection against H5 in
    humans
    ...


    The HI test may not return reliable results for vaccines that provoke types of immunity other than antibody response. That makes it an unreliable measure for the effectiveness of two promising alternative classes of vaccines: live-attenuated vaccines, which have the potential to generate immunity against multiple strains of flu, and inactivated adjuvanted vaccines (those containing a chemical immune-system stimulant), which could help solve the supply bottleneck by allowing much smaller amounts of antigen to be dispensed in each vaccine dose...
  11. by   indigo girl
    The Pandemic Vaccine Puzzle

    Part 4: The promise and problems of adjuvants

    Maryn McKenna Contributing Writer

    "Editor's note: This is the fourth in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 3 discussed the immunologic challenges posed by the H5N1 virus, including its poor immunogenicity when incorporated in vaccines and the difficulty of assessing immune responses to the vaccines."


    http://www.cidrap.umn.edu/cidrap/con...07panvax4.html

    Quote from //www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct3007panvax4.html

    Adjuvanted vaccines appear to hold the greatest promise for solving the grave supply-demand imbalance in pandemic influenza vaccine development. They come with obstacles--immunologic, regulatory, and commercial--but they also have generated more excitement than any other type of vaccine thus far.

    In an example of the hope being hung on adjuvants, the WHO last week issued a statement declaring that the pandemic vaccine supply is "sharply" increasing and forecasting that annual manufacturing capacity will rise to 4.5 billion two-dose courses by 2010.... based on the expectation that flu vaccines made in 2010 will include an adjuvant permitting the use of just one-eighth of current vaccines' antigen content. (Adjuvants are chemicals that are incorporated in some vaccines to improve response to the vaccines' active ingredient. Adjuvants make it possible to reduce the dose of antigen in a vaccine without dampening the immune response.)


    ...they are by definition immune-system activators. ...few have entered the market, because they proved too reactogenic to be acceptable to consumers or safe.Only...aluminum salts or alum (aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate), is licensed in the United States. Aluminum adjuvants and MF59, an oil-in-water emulsion that contains squalene (an oil found in some fish oils), are licensed in Europe...


    No adjuvanted flu vaccine is licensed in the United States--a notable oversight since federal health authorities urged such a vaccine be investigated as a preparedness measure after the pandemic of 1957...Fifty years later, the need to seek regulatory approval for novel components in adjuvanted pandemic vaccines could prove a barrier to rapid market entry of formulas that look promising.


    Like many other aspects of pandemic planning, adjuvants' ability to solve some of the challenges of preparedness will depend on how rapidly a pandemic arrives.


    ...(FDA) has indicated that pandemic vaccines made in the same manner as an already-licensed seasonal vaccine may be treated only as a "strain change," in an accelerated approval process by which components are swapped out of existing seasonal flu vaccines each spring.


    But since there are no adjuvanted seasonal flu vaccines currently licensed in the United States, antigen-sparing pandemic vaccines may require a full Biologics License Application--the complete portfolio of testing and data, on both the product and the manufacturing facility, that is demanded of any new drug submitted for licensure and can take years to assemble...


    ...adjuvants can be brought forward only as part of a precise antigen dose/adjuvant combination that must be tested for safety and efficacy, probably in a "non-inferiority" trial against the same antigen dose without adjuvant, and then submitted for licensure...



    There is currently no regulatory pathway by which adjuvants may be submitted for approval as products by themselves--or may be paired with a separately manufactured antigen, perhaps one produced by another company.


    "There probably are more concerns about an antigen made with one manufacturing process and an antigen made with another manufacturing process and whether when those are mixed with ideal adjuvant X in two potentially different circumstances or time points, that could raise a bunch of issues about formulation, stability, immunogenicity, safety"...
    Last edit by indigo girl on Oct 31, '07
  12. by   indigo girl
    Want to know more about adjuvants? SophiaZoe has some interesting
    commentary. She has also provided links to some posts by Susan C at Fluwiki.

    For those of you that do not know, Susan C is one of the editors at Fluwiki. My
    understanding is that she is a physician living in the UK, and that she
    used to work for the CDC. If this is not correct, I am sure that someone
    will let me know and I will correct the information.

    At any rate, this infomation about adjuvants, vaccine trials, and product testing is eye opening.

    http://birdflujourney.typepad.com/a_...ndemic-va.html
  13. by   indigo girl
    THE PANDEMIC VACCINE PUZZLE

    Part 5: What role for prepandemic vaccination?

    Maryn McKenna Contributing Writer

    "Editor's note: This is the fifth in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 4 examined the possibility of using adjuvants to stretch the supply of pandemic vaccines and the regulatory barriers to that strategy."

    http://www.cidrap.umn.edu/cidrap/con...07panvax5.html

    Quote from //www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct3107panvax5.html

    Experiments with vaccine adjuvants have raised some hope of removing one of the great stumbling blocks to pandemic influenza preparedness: the impossibility of making a vaccine that protects against a pandemic virus before that virus actually emerges.


    A number of the studies that have shown adjuvants may be able to stretch the vaccine supply also demonstrated a secondary benefit: The formulas protected not only against the H5N1 flu strain on which they were based, but against other H5N1 strains as well, a phenomenon called cross-reactive protection.

    ... that could allow production of at least partially protective vaccines well in advance of a pandemic's beginning.


    ...the lag time to the pandemic's emergence might be so long that the vaccination would seem pointless. As well, the vaccine might cause a greater-than-expected rate of adverse events, causing both direct harm to recipients and indirect damage to government credibility--results that would be particularly difficult to tolerate if vaccination proved unnecessary because the pandemic did not arrive. Those risks are not theoretical: They have been demonstrated in the United States twice in recent history, in the abortive 2002 smallpox vaccination campaign and the 1976 swine-flu campaign...


    "...Would receipt of a vaccine prepared before the pandemic be effective in providing some protection or in priming recipients so a single subsequent dose of vaccine would be protective?"


    The most likely and biologically plausible use of prepandemic vaccination would be as the first half of a "prime-boost" series. People would still be given the two doses of vaccine necessary to provoke immunity in a nave individual.


    But the doses would be based on different vaccine strains--the first an early best guess, the second tuned to the pandemic strain
    --and could be given not weeks but months or years apart if the science supported it.


    To achieve prepandemic vaccines, researchers would have to ascertain the right dose and dose interval, determine how long priming lasts, and solve the puzzle of measuring primed immunity.


    Further, regulatory authorities would have to determine the trial design that could deliver those answers, the public discussion that would be necessary for prepandemic vaccines to be accepted, and the safety data that would need to be gathered once the vaccines went into use...


    Recognizing those hurdles, the European Centre for Disease Prevention and Control said in August that while it welcomes
    the development of prepandemic vaccines, it would not support administering them until a WHO declaration of pandemic phase 5 or 6, meaning significant human-to-human transmission is occurring or a pandemic is under way...


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