Posts Tagged ‘fda’

Recombinant Seasonal Flu Vaccine

Monday, December 14th, 2009

The  2009 H1N1 pandemic has highlighted that  however well a nation prepares for the emergence of a new influenza virus strain,  the mechanics of producing the vaccine remain perhaps the greatest obstacle to a successful immunization program. 

The manufacturing process approved in the US for both the seasonal and 2009 H1N1 pandemic vaccine is a lengthy one.  The seasonal vaccine, with its three strains can take at least 8 months from strain identification to becoming available.  The single strain pandemic H1N1 vaccine took 5 months from strain identification to distribution.

The egg-based manufacturing process  requires generation of a seed virus, growth of the virus in eggs, isolation of the hemagglutinin antigen from virus, QC testing of the monovalent bulk antigen, formulation, fill, and finally QC testing of the finished vaccine.  Difficulties that can occur during the process, such as slow virus growth and low yields, both increase the time to vaccine availability and decrease the amount of vaccine available — undesirable outcomes, especially in a pandemic scenario. 

Sure enough, the worst came true for the 2009 H1N1 pandemic vaccine.  Manufacturers encountered both slow virus growth and low yields of hemagglutinin.  During Novartis’s October 22nd third quarter earnings call,  CEO David Vasella stated that the H1N1 strain had yields of about 23% of a normal influenza yield.

The difficulties associated with producing a vaccine from an egg-adapted virus leads to the obvious question of why there is not a recombinant flu vaccine production technology.  Recombinant proteins, which can be produced in weeks rather than months, have been around since the commercial production of insulin by Eli Lilly in 1982. 

To date there are no approved recombinant influenza vaccines, although several are in development.  Protein Sciences’ Flublok, an investigational seasonal recombinant influenza vaccine, which has been discussed before on this blog, is the nearest thing to an approved recombinant vaccine in the US.  It is produced in insect cells using the baculovirus expression system, the same technology used to produce Cervarix, GSK’s HPV vaccine.  Protein Sciences estimates that the cloning,  expression, and manufacture of Flublok can be accomplished in under 2 months. 

Protein Sciences began development of Flublok in the mid ’90s under three different INDs held by the NIH/NIAID, only sponsoring the last five clinical trials themselves.  They finally  submitted their BLA over 10 years later,  in April 2008.   The VRBPAC met on November 19th to review the safety and effectiveness of Flublok.  The committee was asked to answer three specific questions.

  1. Do the available clinical data support an indication in the prevention of flu caused by subtypes A & B included in the vaccine in adults 18 – 49 years of age, 50-64 years of age, and 65 years and older?       
  2. Do the available data support the safety in adults 18 years and older?     
  3. Please comment on what additional studies, if any, should be requested post-licensure 

In summary, the committee was less than impressed.  Members voted in favor of the vaccine for only the 18-49 age group in answer to Question 1, and they voted against the vaccine in answer to Question 2.  Several suggestions were made in response to Question 3, including additional safety studies in subjects over 65 years of age, and properly powered efficacy studies, especially in the over 65 population.

However the committee did recognise the benefit of the potentially faster egg-free production, especially in the context of a pandemic, but these theoretical benefits did not sway the committee in favor of the vaccine.

Given Flublok’s lukewarm debut at the advisory committee it will still be a while before a recombinant seasonal flu vaccine is approved, with the indication likely limited to the the less at-risk 18-49 year old population.  Insurmountable though it seems approval of a recombinant seasonal flu vaccine is not the finish line — people can’t get vaccinated until there is adequate manufacturing capacity to produce the vaccine.

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GSK’s H1N1 Vaccine: A Split Personality

Thursday, November 12th, 2009

Tuesday’s  FDA approval of  GSK’s H1N1 vaccine means all five of the manufacturers  approved to manufacture and distribute the 2009-10 seasonal influenza vaccine (CSL, GSK, MedImmune, Sanofi-Pasteur, and Novartis) are now approved to manufacture and distribute H1N1 vaccines .

The unadjuvanted GSK H1N1 vaccine is actually manufactured in Canada by ID Biomedical Corporation of Quebec, which is owned by GSK.  The process used to produce the hemaggluttinin antigen (HA) is the same as that used for production of the antigen in the seasonal influenza vaccine Fluviral, which has been approved in Canada since 1992 and in the US as Flulaval since October of 2006.

The United States Department of Health and Human Services has placed an order to fill 7.6 million doses of  H1N1 pandemic vaccine from GSK, which will contribute to the approximately 250 million doses secured by the US government.  The vaccine will be produced in multi-dose vials from bulk vaccine manufactured at GSK’s facility in Quebec, Canada.  GSK expects to begin shipping vaccine in December and to provide all 7.6 million doses by the end of the year.

The  HHS order was for $38 million of vaccine, suggesting a cost of $5 for each of the 7.6 million doses.  As discussed in this blog on September 21st, this is in line with the $5.30 per dose paid for the 75.3 million doses contracted from Sanofi, but still a considerable discount to the price of  $10.65 a dose for the 42 million doses contracted from MedImmune.

The GSK H1N1 vaccine is an inactivated split virus influenza vaccine that will be administered as a single 0.5 ml dose containing 15 mcg of antigen.  The multi-dose format of the vaccine packaging necessitates the inclusion of the preservative thimerosal, which is an organo mercury compound with antibacterial properties, included to allow multiple withdrawals to be made from the vial up to a prespecified period of time after the first entry.

In contrast to the unadjuvanted GSK H1N1 vaccine approved in the US,  Canadians will get an oil-in-water AS03 adjuvanted version of the same vaccine,  called Arepanrix.  

After review of the available data on quality, safety, and immunogenicity, Health Canada have concluded that the benefit/risk profile of the Arepanrix H1N1 vaccine is favourable for active immunization against the H1N1 2009 influenza strain and issued a Notice of Decision for the vaccine.  The Minister of Health authorized the sale of Arepanrix on October 21st, 2009 based on the limited clinical testing in humans under the provision of an interim order issued by request of the Public Health Agency of Canada on October 13th.

As described here in earlier blogs about the European pandemic vaccine approval process, Canada employed the mock vaccine approach, developing an H5N1 vaccine in the pre-pandemic period.  Health Canadainspected the antigen  manufacturing facilities, evaluated data from the process, and reviewed both animal and human data from studies performed with the mock vaccine.  Safety and effectiveness of the AS03 adjuvant was also evaluated and deemed acceptable.

Arepanrix H1N1 vaccine is given as a single 0.5 ml intramuscular dose containing 3.75 mcg of hemagglutinin (HA) in the AS03 adjuvant.  As noted above, the HA antigen is manufactured in Quebec by ID Biomedical Corporation of Quebec.

Arepanrix is provided as a two-component vaccine.  One multidose vial contains the antigen and a second multidose vial contains the AS03 adjuvant.   The 10 ml H1N1 antigen vial contains 2.5ml of antigen.  The 3 ml AS03 adjuvant vial contains 2.5 ml of adjuvant.  Prior to injection the entire content of the AS03 vial is withdrawn, added to the H1N1 antigen vial, and mixed.  The mixed final product for injection is an emulsion containing enough vaccine for 10 doses, and contains 50 mcg of thimerosal, which is the equivalent of 2.5 mcg of organic mercury per 0.5ml dose.  This is ten fold less mercury as found in other multidose flu vaccines, probably because the final vaccine vial must be discarded within 24 hours of addition of the adjuvant.  Non adjuvanted multi-dose influenza vaccine vials, such as Flulaval, can be used for up to 28 days after the first entry, therefore typically include 25mcg of mercury per dose.

Now that the  H1N1 vaccines produced by the major manufacturers have all been approved, it’s a good time to survey the regulatory landscape.  As highlighted in this Blog entry, Health Canada has approved an adjuvanted H1N1 vaccine (Arepanrix).  Europe’s EMEA has approved both adjuvanted (Focetria and Pandemrix) and unadjuvanted (Celvapan) H1N1 vaccines.    Finally, FDA has only approved unadjuvanted H1N1 vaccines (GSK, Novartis, CSL, Sanofi, MedImmune), despite the fact that it’s parent organization, HHS purchased nearly $700 million worth of AS03 adjuvant from GSK and MF59 adjuvant from Novartis.

It is not clear why FDA has failed to join other regions in approving the adjuvanted vaccines, especially in the face of the more difficult production of the H1N1 antigen compared to the seasonal antigen.  The AS03-adjuvanted  GSK Arepanrix vaccine approved in Canada requires four-fold less antigen than the corresponding unadjuvanted GSK vaccine approved in the US.  A split personality indeed.

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FDA Approves Four H1N1 Vaccine Products

Monday, September 21st, 2009

Five months after the first reported US case of H1N1 influenza, and 4 months after the declaration of a Phase 6 Pandemic by WHO, FDA has approved four Influenza A (H1N1) 2009 monovalent vaccines.  Three of the vaccines, manufactured by CSL, Novartis, and Sanofi Pasteur, are injectible inactivated vaccines containing 15 mcg of antigen in a 0.5ml dose. They are approved for use as a single intramuscular injection, except in children 4-9 years old (Novartis), and 3-9 years old (Sanofi Pasteur), who require two 0.5 ml intramuscular injections approximately 1 month apart. 

Children 6-35 months old require two 0.25 ml doses of the Sanofi vaccine approximately 1 month apart. Sanofi has gone as far as to produce the vaccine in four different presentations, one of which, the prefilled 0.25ml syringe for 6-36 month olds, is distinguished by a pink plunger rod.  The CSL vaccine is not approved for people under 18 years of age.

The fourth approved vaccine, manufactured by MedImmune, is an intranasal live attenuated virus vaccine containing 10 million FFUs in a single 0.2 ml dose.  A single intranasal dose is recommended for children, adolescents, and adults 10 to 49 years old.  As with the inactivated virus vaccines, children 2-9 years old require two doses approximately 1 month apart.  The MedImmune vaccine is discussed in detail in the August 10th blog posting.

Clinical results that supported the single 15 mcg dose were finally generated by the NIAID’s Vaccine and Treatment Evaluation Units (VTEUs) at the same time as companies began to publish their independently sponsored clinical trial results.  NIAID Director Anthony Fauci reported that, after 8-10 days, a single dose of 15 mcg of the Sanofi Pasteur vaccine generated a robust immune response in 96% of adults aged 18 to 64 and in 56% of adults aged 65 and older.  Similarly, among healthy adults who received a single 15 mcg dose of the CSL Limited vaccine, a robust immune response was measured in 80% of adults aged 18 to 64 and in 60% of adults aged 65 and older.  CSL independently reported similar results from a trial they sponsored in Australia.

The government has ordered 195 million doses of the vaccine, of which about 45 million doses are expected to be available in mid-October.  Of those 45 million doses, it looks like the first available H1N1 vaccine will be MedImmune’s inhaled product.   Approximately 3.4 million doses of the inhalable MedImmune vaccine will be shipped and available in the first week of October. 

The somewhat surprising (yet replicable) outcome that a single 15 mcg dose of the H1N1 vaccine produces a robust immune response in healthy adults ends a lot of speculation on how many doses will be available for the 2009-2010 flu season.  As discussed many times on this blog, the need to go to a higher dose or two shots would have dramatically reduced the already tight vaccine supply; the single 15 mcg dose allows the supply to be stretched further.  Only addition of an adjuvant could further stretch the vaccine supply.

Results from a clinical trial sponsored in Germany by GSK show that a single injection of a 5.25 mcg dose combined with their ASO3 adjuvant  gave a robust immune response 12 days after immunization in 98% of the healthy volunteers aged 18 to 60 years old.  Given the limited global production capacity for the H1N1 vaccine, approval of an adjuvanted H1N1 vaccine, which is likely to occur in Europe, could further boost the global vaccine supply.

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Offshore H1N1 Vaccine Data – Single Shot

Thursday, September 10th, 2009

In early June, Novartis produced the first batch of monovalent bulk H1N1 vaccine.  As discussed in this blog on June 12th, Novartis used cell-culture manufacturing technology instead of the traditional egg-based technology to produce the prototype vaccine, avoiding the delays normally incurred during adaption of the wild-type (WT) virus to grow in eggs.

Novartis have now released top-line information on the performance of this vaccine, called Celtura, in clinical testing.  As speculated, they evaluated the prototype vaccine in conjunction with MF59, their oil-in-water emulsion adjuvant, to see if a dose sparing effect or a shortened regimen could be achieved.  The trial was run at the UK’s University of Leicester and University Hospitals of Leicester in 100 healthy volunteers, aged between 18 and 50.  The vaccine schedule comprised one or two doses of 7.5 mcg MF59 adjuvanted surface-antigen A/California/2009 vaccine.

The pilot trial demonstrated that the MF59 adjuvanted cell culture-based H1N1 vaccine elicited a strong, potentially protective, immune response to Influenza A (H1N1) in 80%  of the subjects after one dose, and in more than 90% after two doses.  Hemagglutination-inhibition titres reached 1:40 or greater in 80 percent of those receiving one dose and more than 90 percent in those receiving two doses. These response rates would satisfy the immunogenicity criteria set by the European and US regulators. Importantly, the vaccine was well tolerated, with pain at the injection site being the most frequent adverse event.

In the same timeframe, Sinovac Biotech, a Chinese Biopharmaceutical company, also began egg-based production of Panflu.1, it’s unadjuvanted H1N1 vaccine, initiating clinical trials in late July.  Again, the top-line results showed good safety and immunogenicity after a single dose.  China’s State Food and Drug Administration (SFDA) organized an Expert Evaluation Conference, and the experts unanimously agreed that the vaccine is suitable for  people 3-60 years old.  SFDA subsequently approved the registration application and issued Sinovac a production license for Panflu.1. The recommended dose is a single shot of 15 mcg in 0.5ml.  The Chinese Central Government has now issued an initial order to Sinovac to purchase Panflu.1 for the national stockpiling plan; 3.3 million doses are required to be delivered by September 15th, 2009.

These company-sponsored clinical trials have demonstrated that an H1N1 vaccine can illicit a potentially protective immune response with a single dose containing 7.5 mcg of an adjuvanted antigen or 15mcg of an unadjuvanted antigen. Similar results should be obtained from the NIAID sponsored trials that are being performed at the VTEUs in the United States.  As luck would have it, the industry-sponsored clinical trial results of a single 15 mcg unadjuvanted dose being immunoprotective ended up being in line with FDA’s recommendations for licensure as described at the July 21st VRBPAC meeting to discuss clinical trials to support the use of vaccines against the 2009 H1N1 virus.

The transcript of the VRBPAC meeting quotes Norman Baylor, the Director of the Office of Vaccines Research and Review, CBER, as stating that FDA has determined that a monovalent unadjuvanted vaccine against influenza A (H1N1) can be licensed as a strain change supplement to existing BLAs, consistent with the approach for seasonal influenza vaccines.  For inactivated vaccines this only requires a submission under the existing license, accompanied by CMC data for the new strain.  Wellington Sun, also of the FDA’s Office of Vaccine Research and Review, goes on to suggest that the H1N1vaccines will initially be unadjuvanted and formulated at 15 mcg per dose.  The complete data from clinical trials of inactivated H1N1 vaccines would be submitted to the BLA post-licensure, with modifications then being made to the product if indicated by the clinical data.  Sun considered this approach to allow for the earliest availability of licensed H1N1vaccine.

A few days after the VRBPAC meeting the Advisory Committee for Immunization Practices (ACIP) met to discuss recommendations for the use of the H1N1 vaccine.  The report has just been issued, outlining the priority group recommended to be the first to receive the influenza A (H1N1) 2009 monovalent vaccine, as it is officially called.  The target group includes 159 million Americans such as pregnant women, health-care and emergency workers and children and young adults aged 6 months to 24 years.

By all indications it appears that sufficient doses will be available for that priority group 45 million, of whom could be vaccinated in mid-October when the 45 million doses are distributed.  The additional 20 million doses expected to be available on a weekly basis after October 15th would allow the ACIP target group to be immunized by the end of the year.

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VRBPAC Meeting on H1N1 Vaccine

Wednesday, July 22nd, 2009

In anticipation of the Vaccines and Related Biological Products Advisory Committee (VBRPAC) meeting scheduled for July 23rd, FDA’s Office of Vaccines Research and Review has issued a briefing document covering the ‘regulatory considerations regarding the use of novel influenza A (H1N1) virus vaccines’.  The document reduces the speculation around the performance of the seed strain virus, H1N1 vaccine timing, clinical studies, and the use of adjuvants.

On May 26th 2009 WHO recommended that novel influenza A (H1N1) vaccines should contain A/California/7/2009 (H1N1)v-like virus.  Five reassortants of this virus (X179A, IVR-153, IDCDC-RG15, NIBRG-121, CBER-RG2) were made available to vaccine manufacturers to prepare seed virus for vaccine production.  The FDA briefing document reveals that initial growth studies suggest the virus yield from the H1N1 reassortants are lower relative to the yields for seasonal influenza vaccines.  Novartis and Baxter have confirmed this.  Novartis has observed the yield for the H1N1 vaccine to be 30% to 50% of that for the company’s seasonal vaccine.  Baxter’s CEO Robert Parkinson has noted that ‘yield optimization’ will be a challenge.  

Since virus yield is directly proportional to the number of H1N1 vaccine doses, a 50% decrease in yield will result in it taking twice as long to manufacture the projected 600 million doses of H1N1 vaccine required to immunize the U.S. population.  Going back to the assumption of the WHO working group on H1N1 vaccines, it is evident that the yield assumption has not been met and hence the total global capacity for vaccine production of 4.9 billion doses over a 12 month period has dropped accordingly.

In addition to yield issues, the briefing document addresses how the availability of potency reagents affects the timing of vaccine availability.  Potency reagents consist of laboratory derived standard antiserum and positive control antigens, and are used in a method called the SRID assay, a somewhat archaic immonodiffusion technique for establishing potency discussed in this blog on May 17th. 

CBER is targeting mid-late July for availability of the reference antiserum and antigen, which would lead to an early August date for the availability of formulated inactivated vaccine for clinical trial material.  Live attenuated viruses, such as that produced by Medimmune, do not require the SRID for formulation and are not subject to the same limitations.  Interestingly, FDA notes that if reagents are not available to formulate the vaccine in time for clinical studies, alternate methods may be considered.  It is not obvious what these other methods are, although the EPAR for Celvapan does describe an HPLC method for hemagglutinin (HA) quantification that was deemed acceptable by CHMP during a  Scientific Advice process.

The clinical studies considerations put forward by FDA are fairly straightforward, although it is noted that if clinical trials cannot be completed in time to inform policy decisions regarding use of the H1N1 vaccine, then FDA will be flexible thus decisions on H1N1 vaccine formulation and use may have to be made based on results from smaller or incomplete clinical studies.

Day 0 and 21 immunizations have been recommended for evaluation in adult and pediatric populations.   Recommended study doses are as expected:  7.5 micrograms and 15 micrograms of HA in the pediatric and adult populations, with an additional 30 microgram dose in the adult population.  The University of Maryland Baltimore Medical School’s Centre for Vaccine Development , part of the Vaccine and Treartment Evaluation Unit (VTEU) will be one of the first sites to lead these studies.  CSL of Australia, who produce a U.S. licensed seasonal inactivated influenza vaccine, announced today that they initiated a trial of their H1N1 vaccine in Adelaide, and expect the vaccine to be proven safe and immunogenic by the end of September.  HHS has ordered $180 million of H1N1 vaccine from CSL.

FDA notes in the briefing document  that there are currently no U.S. licensed influenza vaccines containing an adjuvant, but acknowledges that in the light of both limited global capacity for production of an H1N1 vaccine, and the real possibility that a single dose of unadjuvanted vaccine may not yield an adequate immune response, adjuvants are being considered.  Novartis and GSK will evaluate their oil-in-water emulsion adjuvants for enhanced immunogenicity and dose sparing in separate arms of the adult and pediatric studies.  A dose of 3.8 micrograms of HA in place of the 30 microgram dose is recommended for the adjuvant groups.  HHS recently purchased $344 million of Novartis’ MF-59 adjuvant and $71 million of GSK’s AS03 adjuvant for pandemic use.

Both licensure and Emergency Use Authorization (EUA) are discussed as regulatory pathways for making the H1N1 vaccine available.  Licensure would require the H1N1 vaccine to be manufactured using the same process as a U.S. licensed seasonal inactivated influenza vaccine or a seasonal live attenuated influenza vaccine, and would require the generation of the clinical data described above. The EUA option is more likely for H1N1 vaccines containing the MF-59 or AS03 adjuvants, since no U.S. licensed vaccine contains these adjuvants.

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HHS Orders Around the World

Monday, June 1st, 2009

Health and Human Services (HHS) has inked deals with five flu manufacturers to supply bulk H1N1 vaccine; Australia’s CSL ($180 million), GlaxoSmithKline ($181.1million),  Sanofi Pasteur ($190.6 million), Novartis ($288.8 million), and MedImmune ($90 million).   The HHS funding comes from the $1 billion released for pandemic preparedness on May 22nd to facilitate the manufacture of bulk vaccine.  Another $150 million of this funding will go to the above companies to conduct clinical evaluation of pilot lots for dose, regimen and safety.

Sanofi Pasteur manufactures its bulk flu vaccine at the Swiftwater facilities in Pennsylvania.  CSL will manufacture bulk vaccine in Victoria Australia, GSK in Dresden Germany, MedImmune in Speke UK, and Novartis in Siena Italy or Liverpool UK.    Sanofi Pasteur will be the only manufacturer who produces vaccine on US soil.   So if the Stage 6 H1N1 pandemic comes to pass both the virus and the solution will be global.  There isn’t enough local capacity for national vaccine production, as has been seen historically for seasonal vaccine production, and was so clearly highlighted by the Chiron supply failure in 2004. 

WHO predicts the top end of global H1N1 capacity to be 4.9 billion doses over a 12 month period after full-scale production is initiated.  The two assumptions underlying this prediction are that there is a vaccine yield equivalent to that routinely obtained for seasonal vaccine, and that there is the use of the most dose-sparing formulations.

WHO must be banking on vaccine manufacturers to produce adjuvant-containing formulations for dose-sparing.   Apparently HHS has heard the call; the H1N1 orders to GSK and Novartis included an order for their proprietary adjuvants, AS03 and MF59C.1 respectively, both squalene containing oil-in-water emulsions that can significantly decrease the dose of antigen needed to produce the required immune response.  Since both can be added to the antigen at the time of administration, adjuvant production is decoupled from that of the antigen;  there is no need for coformulation.  This mitigates the risk of an untested, adjuvanted flu-vaccine being the solely produced pandemic vaccine.  FDA is likely to approve the H1N1 antigen‑alone formulation which could be distributed without the adjuvant in the case of a pandemic.

HHS’ hedge still has a silver lining.  Perhaps egged on by its parent organization, FDA will approve an H1N1 flu vaccine containing a novel, non-alum, adjuvant as discussed in this blog on 18th May 2009.  This would be a winner.

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H1N1’s Billion Dollar Start

Wednesday, May 27th, 2009

$1 Billion has been released from funds set aside for pandemic influenza by the HHS to begin the process of manufacturing the H1N1 influenza vaccine.  The money will fund the efforts of vaccine makers (such as Novartis and Sanofi Pasteur) to make bulk vaccine that can be held in a federal stockpile.  The bulk vaccine could then be used if the decision is made to move forward with wide-scale vaccination against the H1N1 flu virus.

What precisely will the billion pay for?  Presumably the production of pilot lots of H1N1 vaccine that can be used in human clinical trials to establish both immunogenicity and the dosing regimen most likely to offer protection against the currently circulating H1N1 strain.  This process occurs every year for the seasonal vaccine.  Just look at the package insert for a U.S. FDA approved seasonal trivalent influenza vaccine (TIV), and you will see that pilot lots of the vaccine are tested, and seroconversion, geometric mean hemagglutinin inhibition antibody titers (HAI), and adverse events (AE) are reported for these lots.  Based on this data FDA approves the company’s supplement to the Biologics License Application (BLA) for Influenza Vaccine.  The vaccine is then available for public use.

Regulatory expectations for the pandemic vaccine are the same.  Perhaps fueled by the Avian Flu scare, in May 2007 FDA issued a guidance on the ‘Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines’.  They stated that approval of a pandemic influenza vaccine for manufacturers of a U.S. licensed seasonal inactivated influenza vaccine, where the process for manufacturing the pandemic influenza vaccine is the same as for the licensed seasonal product, will require clinical immunogenicity trials to determine the appropriate dose and regimen of the pandemic influenza vaccine candidate.  FDA also requires these trials to include an assessment of safety.

It should be noted that the 2007 FDA guidance also outlines a pathway to approval for Adjuvanted Influenza Vaccines, which were discussed on this blog on 18th May 2009. This raises the question: will manufacturers take the bold but risky regulatory path of adding adjuvants to the pilot lots of H1N1 vaccine to be tested in the human clinical trials? Recall from my 18th May 2009 blog entry that these non-alum adjuvants remain unapproved by FDA despite reams of safety and manufacturing data collected over decades. I believe a piece of the billion-dollar pie should be used to evalute these adjuvants in the pilot pandemic vaccine. Adjuvanting the H1N1 strain could spare valuable doses and maximize the effectiveness of the limited amount of material that is likely to be produced to accomodate both the seasonal and pandemic flu. I hope that the new leadership at FDA recognizes the potential public health emergency and acts with a sense of urgency and pragmatism to encourage the use and approval of these adjuvants in the H1N1 pandemic flu vaccine.
 
Will FDA rise to the occasion? That is the billion dollar question

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