SAN FRANCISCO -- The nation's anxiety over the dwindling supply of flu shots has exposed an antiquated manufacturing system that depends on 90 million fertilized chicken eggs and a 9-month process to produce each year's batch of influenza vaccines.
It needn't be that way.
Drug companies and academic researchers say they could reduce the lead time and prepare more effective vaccines by incubating the virus in monkey cells rather than eggs -- and by using genetic engineering to remove much of the guesswork of preventing a disease that kills an average of 36,000 Americans a year.
Government indifference, business resistance and public apathy have slowed the adoption of such techniques, vaccine researchers say. But that may change soon now that federal health officials have responded to the vaccine shortage with calls for overhauling the system.
"In order to scale it up, or to speed it up, we would have to, really, change the overall approach to vaccination," Centers for Disease Control and Prevention director Julie Gerberding said recently, endorsing the monkey cell process as an important alternative.
The federal interest heartens researchers like Dr. Richard Webby, who has labored in relative obscurity for years trying to speed up production of better vaccines.
Webby's work has gotten a lot more attention since it became known that this year's flu vaccine doesn't contain the prevalent strain of the virus going around. The world's two largest manufacturers subsequently announced they had run out of supplies for the first time, even as flu deaths mounted.
Each February, World Health Organization doctors meet with an international team of virologists to identify the flu strains they think will hit the following winter. They then brew these flu strains in chicken eggs to create a safe "seed vaccine."
It can take months for the eggs to yield the seed vaccine, and until the vaccine makers receive the seed and related biological material from the World Health Organization, they can't begin the manufacturing process in earnest.
Webby and colleagues at St. Jude's Children's Research Hospital in Memphis, Tenn., hope to speed development of each year's vaccine through "reverse genetics," which aims to build from scratch perfect flu strains that reproduce reliably and quickly.
"Although the viruses still have to be grown up in eggs to make vaccines, the initial process of making seed vaccine is much quicker using reverse genetics," Webby said.
An even bigger time-saver will come from growing the vaccine in vero cells -- taken from the kidneys of African green monkeys -- instead of the chicken eggs, Webby and many others say.
Using vero cells isn't new -- they've already been used to make a polio vaccine approved in the United States, and a smallpox vaccine using vero cells is in the works.
At least two companies, Chiron Corp. and Baxter International, plan large-scale human experiments next year with cell-made vaccines. Each hopes for U.S. regulatory approval in 2007 or soon after.
"There is a certain limitation on how many eggs you can get in a timely manner," said Wayne Morges, a Baxter vice president. "You can't go to the chicken and say 'lay faster.' We can make course corrections easier with cells."
Baxter of Deerfield, Ill. is putting the finishing touches on a new factory in the Czech Republic to brew its new vaccine recipe. Baxter hopes to have European approval in time for the 2005 flu season.
Emeryville-based Chiron and the French-owned Aventis Pasteur make the only egg-based flu vaccines approved for use in the United States, and since cell-based vaccines remain years away from the market, Chiron isn't ready to abandon the egg-based process.
"It does have the potential to reduce that time, Chiron spokesman Rod Budge said. "But it's not going to produce vaccines overnight."
Egg-incubated vaccines will remain the dominant product for at least the next few years not only because of regulatory issues but also because building new factories will take time and money.
Baxter also conceded that its initial vaccine shots will cost more than the ones currently available.
Aventis Pasteur remains resistant to changing its egg-based process. Aventis spokesman Len Levanda argues that the number of new factories and fermenters needed to satisfy demand for the flu shots are not available and will be expensive to build.
Also, he said, this flu season is the first in which demand outstripped supply -- it may turn out to be an anomaly.
"This is unprecedented because we can't remember a time when we ran out of flu vaccine," Levenda said. "Public health needs will continue to be best met by egg-based vaccines."
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