Posts Tagged ‘HHS’

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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HHS Purchases More MedImmune H1N1 Vaccine

Monday, September 21st, 2009

Back on August 10th I discussed MedImmune’s intranasallive attenuated H1N1 influenza vaccine and the potential for a dose surplus.  HHS had contracted for 12.8 million doses of the vaccine at a cost of $151 million, with MedImmune having the production capacity to make up to 200 million doses by March 2010. However, MedImmune had only sufficient Accusprays to fill approximately 40 million of these doses in the same timeframe.

The U.S. Department of Health and Human Services (HHS) has now ordered an additional 29 million doses of MedImmune’s H1N1 vaccine, which when added to the original 13 million dose order, accounts for all of the Accuspray delivery devices.

The total contract value is now about $447 million for the 42 million doses, or $10.65 a dose.  HHS also ordered an additional 27.3 million doses of injectible inactivated vaccine from Sanofi Pastuer at a cost of $143.5 million.  The Sanofi contract is now at $396 million for 75.3 million doses, or $5.30 per dose, a condsiderable discount to the MedImmune price.

MedImmune began developing the vaccine at the end of April, and about 3.4 million doses have been released by the FDA. They are expected to be shipped to states the first week in October.

MedImmune was in discussions with FDA to define a path for an alternative delivery device, possibly a dropper, to optimize utilization of the additional bulk vaccine capacity, which appears to be about 150 million doses.  This entails working with FDA’s CBER to gain the regulatory approvals needed for an alternative delivery device.  Since HHS only purchased the amount of H1N1 vaccine for which there are sufficient Accusprays, the fate of the excess capacity remains unknown.

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Low-Tech Solution to the Flumist A (H1N1) Dose Surplus

Monday, August 10th, 2009

MedImmune’s Flumist™ seasonal flu vaccine differs from the five other seasonal flu vaccines approved for use in the U.S. in two significant ways. First, it is a live attenuated influenza vaccine (LAIV), not an inactivated split or subunit vaccine. Secondly, it is administered intranasally via a special syringe that introduces large-particle aerosol droplets of the vaccine to the nasal mucosa.

The vaccine was approved by FDA in 2003 for active immunization for the prevention of disease caused by influenza A and B viruses in healthy children and adolescents, 5-17 years of age, and healthy adults, 18-49 years of age. In 2008, FDA approved expanding the population to include children between the ages of 2 and 5. 

The virus is attenuated, or weakened,  by inserting genes that confer the properties of cold adaption (ca) to efficient replication at 25°C, growth-restriction at 37°C (rt) for the Type B and 39°C for the Type A strains, and limited replication in the lungs of ferrets (att).  These genes come from the master donor virus strains ca B/Ann Arbor/1/66 and ca A/Ann Arbor/6/60.  The seed virus used for annual production of the seasonal vaccine is a 6:2 reassortant produced by reverse genetics.  There are 6 internal genes from the attenuated donor virus, and the HA and NA genes from the wild type virus.

When administered intranasally, the LAIV induces both serum and mucosal antibodies, an immune response that closely resembles the body’s natural response to influenza infection, but does not cause illness.  The syringe that delivers the intranasal dose is the BD AccuSpray, which is based on the BD Hypak SCF (sterile, clean, ready-to-fill) technology.  The total dose is 0.2 mL.  The plunger is installed with a dose-divider clip which only permits 0.1ml to be delivered to the first nostril when the plunger is depressed.  The clip is then removed so the plunger can be further depressed and deliver the remaining 0.1 mL dose to the second nostril.

In response to the H1N1 pandemic, HHS contracted with Medimmune for 12.8 million doses of the H1N1 strain of Flumist at a cost of $151 million.  Apparently Medimmune’s virus strain grew well; 20 million doses have already been produced, and the company projects they could produce up to 200 million doses by March 2010.  Unfortunately there are only sufficient Accusprays to fill approximately 40 million of these doses by March 2010.  BD has said it will run its sprayer factory around the clock to increase annual production from 20 million sprayers to 70 million.  However this would still leave a significant surplus of doses that cannot be filled.

Medimmune is working to define a path for an alternative delivery device, possibly a dropper, to optimize utilization of the additional bulk vaccine capacity.  This entails working with FDA’s CBER to gain the regulatory approvals needed for an alternative delivery device.  The dropper was used to deliver the vaccine in some of Medimmune’s earlier clinical trials.

Medimmune plans to conduct two concurrent placebo-controlled clinical studiesof the H1N1 candidate in 300 adults 18-49 and 300 children 2-17, using a two-dose schedule one month apart. They expect to have safety data from the first dose by early September and 29-day immunogenicity data by mid-October.  They expect to have safety data from the second dose by mid-October and 29-day immunogenicity data by early November. 

The Flumist device bottleneck highlights the supply chain challenges that will occur during the response to the pandemic, one that was clearly not anticipated in the case of Flumist. As discussed in this blog on May 20th, the Department of Health and Human Services had the foresight to recognize the criticality of the egg supply and awarded a contract to Sanofi Aventis to ensure there are enough eggs on hand to manufacture flu vaccines in the event of a pandemic flu outbreak or future vaccine shortages. 

Fortunately, in this case, the decidedly low-tech dropper may save the day.  The potential surplus of Flumist can then be used to expand the U.S. supply or provided to other countries.

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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 Backs A Recombinant Baculovirus H1N1 Vaccine

Wednesday, June 24th, 2009

Virtually all flu vaccines are produced from influenza virus grown in embryonated eggs.  The technology is slow and dependent on a supply of suitable eggs, so in recent years a cell-culture technology has been developed that is egg-free and faster than the egg- based method.  Cell-culture technology still requires live influenza virus as the seed stock for the manufacturing process, but does not require adaption of the virus for growth in eggs.

A third production technology is now in late-stage development; recombinant influenza vaccine produced in baculovirus-infected insect cells.  Health and Human Services (HHS) has awarded a $35 million contract to Protein Sciences Corporation , a US-based pioneer of baculovirus technology that has been developing such a recombinant influenza vaccine.  The award is under the National Strategy for Pandemic Influenza Implementation Plan, which calls on HHS to develop and procure medical countermeasures for pandemic influenza or for potentially pandemic strains, such as the recent H1N1 flu virus.  The thinking behind the HHS award is that recombinant technology  will help meet surges in demand for U.S.-based vaccine, such as is being seen for the H1N1 flu vaccine. 

Because there is no requirement for live influenza virus in the production of the Protein Sciences recombinant vaccine, the vaccine could more quickly progress through the prototype vaccine, clinical investigational lots, and commercial-scale production steps in comparison to the traditional egg-based vaccine.  In addition, the insect cells can be frozen for ‘on demand’ use, simplifying the supply chain and decreasing  the start-up time for production

Simply put, once the sequence of the flu virus strain is available, a strain-matched hemagglutinin gene encoding recombinant baculovirus seed lot is generated.  This is the time-saving step.  An  S. frugiperda insect cell line is then infected with the recombinant baculovirus and grown to a high cell density.  Finally the hemagglutinin (HA) antigen is purified from the disrupted cells and formulated to produce the finished vaccine. 

Interestingly, the Protein Sciences’ FlubloK seasonal influenza vaccine made by the recombinant process, and for which a Biologics License Application (BLA) is currently under review at FDA, is formulated to contain 45 micrograms of each HA strain.  This is three times the amount found in all other manufacturers’ seasonal flu vaccines, which contain 15 micrograms of each HA strain.  This suggests recombinant HA produced using the baculovirus expression system is less potent than the live virus-derived HA.

FDA has not yet approved a flu vaccine produced by recombinant technology; in fact FDA has yet to approve a product produced using the baculovirus expression system.  Only one baculovirus expression system-produced vaccine has ever been approved for human use, and that is Cervarix, manufactured by GlaxoSmithKline Biologicals.  EMEA granted marketing authorisation by on the 20th September 2007 for the prevention of premalignant cervical lesions and cervical cancer causally related to Human Papillomavirus (HPV) types 16 and 18.

If and when FDA approves this recombinant technology, the HHS contract requires Protein Sciences to establish domestic manufacturing capability to provide a finished vaccine within 12 weeks of the onset of a pandemic and to produce at least 50 million doses of pandemic flu vaccine within six months of pandemic onset.  With a U.S. population of over 300 million and and a very limited domestic flu vaccine capacity, the $35 million Protein Sciences award is a significant step forward in building a domestic vaccine supply chain.  Getting a baculovirus-derived product approved by FDA, and increasing the portfolio of proven production technologies, is a big bonus.

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Phase 6 Influenza Pandemic Announced and a Prototype H1N1 Vaccine Arrives on Schedule

Friday, June 12th, 2009

The H1N1 influenza strain has spread from person to person and country to country and, as expected, the scientific criteria for an influenza pandemic have been met.  The WHO has raised the influenza pandemic alert from phase 5 to phase 6, signaling the start of the 2009 influenza pandemic -  the first in 40 years.

In apparent lock step with the announcement of Phase 6, and weeks ahead of expectations, Novartis has produced the first ten litre batch of monovalent bulk vaccine.  It is derived from the wild-type H1N1 virus that the CDC supplied back in early May.  Novartis used cell-culture manufacturing technology instead of the traditional egg-based technology to produce the prototype vaccine , avoiding the delay incurred while having to adapt the wild-type (WT) virus to grow in eggs. 

The Novartis produced vaccine is only a prototype because the CDC’s reassortant virus seed (not WT) must be used for routine production of flu vaccine.  The reverse genetics reassortant is carefully screened and selected for quality and safety using  controlled and documented methods .  The wild-type prototype vaccine can however be used for preclinical evaluation’ which may lead to early information on the dose and regimen needed for an H1N1 vaccine.  The wild-type prototype vaccine will probably also be tested with an adjuvant to see if a dose sparing effect or a shortened regimen can be achieved.  CDC’s Anne Suchart has already stated that they are aware that an H1N1vaccine will require “a lot of antigen to get the response”. 

Novartis received the  reverse genetics reassortant seed virus from CDC on May 27th, and expects to enter human clinical trials with the resulting vaccine in July, receiving WHO licensure in the fall of 2009.  The studies could be completed within 2 months, and licensure could be granted by October, assuming that one and two dose immunization schedules are evaluated and immunogenicity is measured approximately three weeks post second immunization.

Only about 5% of the worldwide flu vaccine capacity employs cell culture technology so Novartis’ early competitive advantage will quickly dissipate as the egg technology vaccines begin to emerge from the likes of  Sanofi Pasteur and GSK.  Even the majority of Novartis’ capacity is egg technology, based in Siena Italy and Liverpool UK.  Their cell-culture facility is in Marburg Germany, while a second facility is under construction in Holly Springs North Carolina.  By approximately 2012 the HHS funded Holly Springs facility is anticipated to be capable of producing 150 million doses of pandemic vaccine within six months of the declaration of an influenza pandemic.

Novartis’ cell-culture H1N1 vaccine is a taste of the future.  The vast majority of the H1N1 vaccine will be produced in eggs this time around, as discussed in this blog on May 20th.  It took 40 years for this pandemic to arrive; cell-culture based flu vaccines should be ubiquitous next time around.

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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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