WASHINGTON, July 21 -- The FDA will be extraordinarily flexible in evaluating vaccines for pandemic H1N1 influenza, suggested an agency briefing document issued for an upcoming advisory committee meeting.
On Thursday, the Vaccines and Related Biological Products Advisory Committee will hear about the status of H1N1 vaccine production, as well as the FDA's plans for evaluating vaccines in time for the fall flu season, when public health officials expect to see resurgent H1N1 infections.
It's expected that at least one vaccine will be available for clinical test by late summer. The National Institutes of Health has said it would like to begin vaccinating certain high-risk groups, such as healthcare workers, by mid-October, which doesn't leave much time for the FDA to approve a vaccine. (See H1N1 Summit: October Target Date for H1N1 Vaccine Distribution and WHO Says Healthcare Workers Are H1N1 Vaccine Priority)
Normally, clinical trials are completed before the FDA would even accept an application for a drug or vaccine. But given the perceived urgency of the H1N1 situation, the agency might approve a vaccine based on incomplete or very small studies, according to a briefing document from the FDA's Center for Biologics Evaluation and Research Office of Vaccines Research and Review.
In fact, the document suggested, the agency might even waive its customary demands for compelling safety and immunogenicity data.
The government expects Novartis, Sanofi Pasteur, CSL, and GlaxoSmithKline to supply inactivated H1N1 vaccines to the U.S. market, while MedImmune will produce a live attenuated H1N1 vaccine, according to the document.
The FDA said it would like the sponsors of the study to perform double-blind or observer-blinded studies in which patients are administered two doses of the vaccine, 21 days apart.
Manufacturers should stratify their patients into four age groups: infants and toddlers, ages 3 to 9, 18- to 64-year-olds, and older than 65.
The FDA did not request an adolescent group because those data can be interpolated from the other age groups, the document said.
It also didn't specify a study protocol for babies less than six months, because such studies will have to be designed to evaluate the entire series of infant vaccinations.
The FDA said that 100 patients in each arm of the trials "is sufficient to provide a description assessment of immunogenicity with a reasonable degree of confidence in that estimate." If a control arm is used, it should contain at least 25 patients.
The FDA recommended that patients should be followed for six months after the second vaccination to monitor for serious adverse events, and for one year if the second vaccine contains an adjuvant, the FDA said.
The vaccine will be considered as having an immunogenic response if:
•The lower bound of the two-sided 95% confidence interval for the percentage of subjects achieving seroconversion for H1 antibody should meet or exceed 40%, or 30% for those over 65.
•The lower bound of the two-sided 95% CI for the percentage of subjects achieving an H1 antibody titer more than or equal to 1:40 should meet or exceed 70%, or 60% for those over 65.
The FDA will be working with manufacturers and government agencies to coordinate surveillance plans, according to the briefing document.
It is expected that the National Institutes of Health will also sponsor some H1N1 vaccine studies, and the agency will present its plan to the advisory panel on Thursday.
According to the briefing document, the FDA is considering vaccines from Novartis and GlaxoSmithKline that use dose-sparing, oil-in-water adjuvants to stretch the quantity of the antigen farther.
There are currently no licensed influenza vaccines that contain an adjuvant, and if the FDA decides to approve a vaccine with an adjuvant, it would have to issue "emergency use authorization," which would allows emergency use of products that "may be effective" in preventing serious or life threatening disease.
Normally, emergency use authorization is issued when the FDA commissioner determines there are no available alternatives, but in this case, the commissioner could issue the emergency use authorization if there are insufficient supplies to meet the emergency need, according to the briefing document.
The advisory panel is not being asked to vote formally on specific questions. It will hear an update from the FDA, an update from the five vaccine manufacturers, and it will discuss the FDA's trial protocol recommendations.
hat-tip Marina
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