Egging on the flu vaccine

The October 5 announcement by the Chiron Corporation that it could not ship nearly half the US supply of influenza vaccine has trained a spotlight on the vaccine production process. The ensuing public frenzy was abetted by a frightening flu season last year, stronger CDC recommendations on infant immunization, the looming threat of avian flu, and a harder push from public health groups for vulnerable populations to get immunized.The shortage, say experts, illustrates the drawbacks of relying on chicken eggs to produce a hundred million doses of influenza vaccine each year, and the weakness of the existing supply system. Government and industry are scrambling to find alternatives to the egg method, and while these hold promise for shortening the production cycle and adding "surge capacity," it's not clear if the fundamental change experts say is needed to truly address the system's weaknesses will take place. "It's a wakeup call we don't seem to be waking up to," says Paul Offit of Children's Hospital of Philadelphia.Cell-culture production is the leading alternative candidate to eggs, with many attractive features, says Geoffrey Porges, a senior biotech analyst at Sanford Bernstein who used to run Merck's vaccine marketing business. Advantages of using cell cultures include the potential for a two- to three-month production cycle (rather than the current six to nine months), better control of the production process, less likelihood of contamination, and less expense.Contamination is clearly an issue in the flu vaccine production business; it's why Chiron suspended its production. And according to an Oct. 25 Newsday article, the Food and Drug Administration (FDA) has warned at least three flu vaccine manufacturers since 2000 that their production facilities were out of compliance with federal regulations.Aventis is now partnering with Crucell, a small Dutch biotech, to develop a flu vaccine production method based on human retinal cells. Chiron is working on technology using cell lines from dog kidneys. Baxter International already produces smallpox vaccine using a cell culture based on African green monkeys, and late next year in Europe the company plans to release a flu vaccine made with the technology.Cell culture isn't the only alternative to egg production, notes Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. One approach, for example, would use recombinant DNA vectors to produce purified hemagglutinin and neuraminidase components.While Offit agrees that cell cultures would shorten the flu vaccine production cycle, he's not sure that the reduction would be that dramatic, or that the process would be any cheaper. And no matter how the vaccines are produced, he adds, the economic weakness of the vaccine business remains. Given FDA requirements for vaccine production, small companies who would be happy to make a couple of hundred million dollars a year producing vaccines can no longer stay in the business. Also, the market is fairly unattractive for large pharmaceutical companies able to make billions from drugs for high cholesterol, baldness, and erectile dysfunction.Porges argues that the federal government should subsidize vaccine makers, just as it helps fund services such as public transportation and utilities or pays farmers to maintain agricultural capacity. Offit says the government has three options: paying more into the Vaccines for Children program, the single largest US purchaser of vaccines; mandating higher payments for vaccination from insurance companies; or subsidizing the industry."I don't like to use the word subsidy," says Fauci. He prefers "guaranteed purchase," meaning the government would agree to pay vaccine makers for a certain number of doses each year, whether or not they are used.Funding for flu vaccine research in general has climbed from $22 million to more than $60 million over the past four years, with $11 million specifically targeted at alternatives to egg production. But the NIH is also putting money into improving the reliability of egg-based vaccine production, and it will be many years before the old technology can be replaced, Fauci says.Even with the shortage, it's unlikely this flu season will be severe, since last season's was so harsh. But Porges says he's worried about next year, when the likelihood of a substantial drift in the viral strain is much greater. Offit says he foresees plenty of flu vaccine next season, and a return to low demand. "This year is more like the Beanie Baby phenomenon," says Offit. "I think people are desirous of the vaccine because they see it as a limited edition."But Fauci says he's optimistic that the crisis will prove a real wake-up call to Congress and the public on the need to reform the system. "We in the public-health sector have been pushing for years to revitalize the vaccine industry," he says. Now, he hopes, legislators and their constituents may finally be ready to tackle the problem.- Anne Harding

Egging on the flu vaccine

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