FDA's decision on whether to approve an adjuvanted H1N1 influenza vaccine will likely come down to the wire, as manufacturers and the National Institutes of Health scramble to produce the immunogenicity data necessary to justify use of adjuvants for mass vaccination.

At a July 23 meeting, FDA's Vaccines and Related Biological Products Advisory Committee gave the agency no hard advice on whether or not to approve adjuvanted H1N1 vaccines. They were instead tasked with advising the agency on whether it is correctly approaching the licensure and regulatory pathway for the products.

How FDA licenses H1N1 flu vaccines depends on whether adjuvants are needed: unadjuvanted vaccines would be licensed under the strain change process used annually for seasonal flu vaccines. If adjuvants are needed to provide an extra immune boost, the firms that produce adjuvented products (GlaxoSmithKline and Novartis) would gain licensure under an Emergency Use Authorization (Also see "Flu Vaccine Licensure Depends On Adjuvant; Fall Vaccination Campaign Likely" - Pink Sheet, 13 July, 2009.).

But with a mass vaccination campaign likely in the fall and trials of vaccine candidates just beginning, it is unclear whether that immunogenicity data will be available in time to support use of an adjuvanted product.

That final data could come at any point from late September (if all goes perfectly) to January or later if the trials hit road bumps (which the panel said was likely). The Department of Health and Human Services has contracted with five seasonal flu manufacturers to produce the vaccines.

Government officials told the panel that when FDA is able to make a determination on the need for adjuvants depends on whose crystal ball you consult. Since FDA has been reluctant to approved them - out of concern for giving a relatively untested ingredient to an otherwise healthy population - industry is watching with great interest to see whether the pending pandemic will force a regulatory decision (Also see "H1N1 Vaccine With Adjuvant Would Need Twice The Follow-up, FDA Recommends" - Pink Sheet, 21 July, 2009.).

In the meantime, FDA is prepared to license unadjuvanted vaccines as a strain change, and the panel expressed unanimous comfort with this method. This H1N1 pandemic breaks from the typical strain change process in that FDA is requiring the additional clinical data.

The two major reasons to consider using adjuvanted H1N1 vaccines are their ability to boost immunity and spare the necessary doses of antigen - of particular concern if virus yield is too low to produce adequate doses of vaccine. Further supporting use of adjuvants is that they have been approved in Europe for over a decade and produced no safety signals.

Though the panel did have concerns about releasing a previously-unapproved product for widespread use, they were also excited about the possible additional efficacy and reach adjuvants provide. "I don't want FDA to walk away from this meeting thinking we're all afraid of adjuvanted vaccines. Speaking for myself, I'm delighted that the option is there," said Theodore Eickhoff, University of Colorado.

No votes were taken at the meeting, as there are too many uncertainties at this point for final determinations to be made. FDA instead sought general input, and in addition to licensure and use of adjuvants, the agency asked the panel about whether the vaccines should be administered in one or two doses, considerations for immunizing special populations (such as infants under six months of age and pregnant women), post-licensure safety evaluation, and approaches to assessing vaccine effectiveness.

Those are just a few of the critical decisions that will have to be made over the coming weeks and months concerning how the possible pandemic will be managed. Discussions concerning the recommendations for use and immunization programs are ongoing by other committees, including CDC's Advisory Committee on Immunization Practices, which will meet July 29 in Atlanta.

As of July 16, in the U.S. there have 40,617 lab-confirmed cases of H1N1 influenza, including 4,795 hospitalizations and 262 deaths.

-Jamie Hammon (j.hammon@elsevier.com)

Adjuvanted H1N1 Vaccine Excites FDA Panel, But Jury Is Still Out

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