Strategies In light of potential pandemic

for preventing another shortage3Public health experts have warned for years that the USA's vaccine supply system is resting on shifting sands. For most of us, those warnings have been little more than background noise.

But this year's shortage of flu vaccine has raised the volume enough that ordinary people finally are listening. The system is damaged. Now, how do we fix it?

The question is not an idle one. Strains of flu that circulate every winter kill an estimated 36,000 people a year in the USA and hospitalize about 200,000. Of even greater concern are ominous signs that the world is on the verge of a global flu pandemic caused by the emergence of a new strain of the virus, one to which everyone would be vulnerable.

If we can't provide enough vaccine to protect people from garden-variety flu, many ask, what would happen in a global pandemic?

USA TODAY's Anita Manning asked experts in public health, industry, government and academia what should be done now to strengthen the vaccine supply so we don't have another year in which seniors are forced to wait in lines for hours for a routine flu shot. To strengthen the system, they advise, three things need to be done:

Boost the demand

Flu vaccine makers produce only as much as they think they can sell. If they sold out every year, they'd build more plants and make more vaccine. But so far that hasn't happened. Even though more vaccine is produced every year and more people are immunized, fewer than half of those for whom flu shots are recommended get them. Only 36% of health care workers -- the first line of defense in an outbreak -- are immunized each year.

This year, the Centers for Disease Control and Prevention estimated that 100 million doses of vaccine would be available. In October, when the British government suspended Chiron's license because of contamination at its plant in England, the expected supply was reduced by about 48 million doses.

Aventis Pasteur planned to produce nearly 55 million doses and says it will be able to squeeze out 2.6 million more by mid-January, but that is all it can do. The plant is going full steam, and because flu vaccine is made by growing virus in chicken eggs, it takes about six months to produce each year.

Every year, millions of doses of vaccine are discarded. Last year, flu struck early in many parts of the country, sparking a run on vaccine and causing flu-shot makers to sell out, but MedImmune still wound up tossing about 4 million doses of FluMist, the nasal-spray vaccine.

''On average, we destroy 15% of the vaccine we make every year,'' says Len Lavenda of Aventis. ''We have to make a decision about how much vaccine to produce long before we know how much vaccine will be administered.''

Most people follow their doctors' suggestions, but doctors may have little financial incentive to promote flu vaccine, says Duke University economist Frank Sloan. Medicare pays $8 to doctors for administering flu shots, although the price will jump next year to $18 a shot.

''It's easier when the patient is in the office for something else to say, 'Hey, you need flu vaccine,' '' Sloan says. ''But if the doctor is not interested because he's not being paid enough, he'll say 'go to the public health department or to the Wal-Mart.' ''

One barrier to vaccination is that most people don't fear flu because it's familiar, says David Ropeik, director of risk communication at the Harvard Center for Risk Analysis. People shrug off flu warnings, he says, but don face masks to prevent SARS.

It's also a disease that is around every year, making it ''less compelling than one which is catastrophic, which kills lots of people at once in one place,'' he says. ''So we're afraid to fly, but we're not afraid of the flu.''

What prompted long lines of people waiting for hours at flu-shot clinics in October was the knowledge that there is not enough to go around. It meant that ''we've lost one way to control our health,'' Ropeik says. ''When we have control, we're less afraid; when we lose control, we're more afraid.''

Encourage vaccine production

Like so much in life, it all comes down to money, experts say. Vaccines are difficult and expensive to make, highly regulated and produce relatively low profits.

Worldwide, about a dozen or so companies make flu vaccine. Only two make flu shots for the United States: Aventis and Chiron. A third, MedImmune, makes FluMist, a nasal-spray vaccine that is licensed only for healthy people ages 5 to 49. About 3 million doses of FluMist will be produced this year.

''We would like to see the price for flu vaccine continue to increase to better reflect escalating costs of production,'' which include investments in new technologies and rising quality standards, and to ''reflect the value of vaccines,'' says Aventis' Lavenda.

Flu-shot prices have risen in recent years, but they still cost less than $10 a dose. The nasal-spray vaccine costs about $23 a dose or less, half what it sold for last year. Doctors add their administrative costs to the price, so most people wind up being able to get a flu shot for around $20-$25, more for FluMist.

One of the biggest customers for flu vaccine is the government's Vaccines for Children program, which negotiates lower prices because of its buying power. This year, about 5 million doses were bought for the program. A shot might cost a doctor $8.50, but the Centers for Disease Control and Prevention pays $6.80 for the same dose.

This is both good and bad, says Mark Pauly, chair of the Health Care Systems Department at the University of Pennsylvania's Wharton School. ''They did what we want them to do. They bargained hard and got a discount. But the consequence is that this is a product that manufacturers are not particularly interested in supplying,'' Pauly says. ''It's possible to pay too little for a pharmaceutical product, as well as too much.''

Health and Human Services Secretary Tommy Thompson says his department is trying to lure new vaccine makers into the U.S. market, promote new technologies and support existing ones.

The agency recently bought 1.2 million extra doses from GlaxoSmithKline in Europe and awarded $10 million to Aventis to purchase a year-round supply of eggs so vaccine can be made more quickly if needed. It also has requested $125 million for flu-pandemic preparedness in the next budget.

Bruce Gellin, director of the National Vaccine Program Office, says U.S. regulators have inspected vaccine plants, reviewed scientific files and talked to companies about what is needed for their products to be licensed in this country. ''What we're trying to do is have a broader manufacturing base so in case a manufacturer has a problem, the impact is less,'' he says.

Klaus Stohr of the World Health Organization says experts at a recent conference agreed that a single international licensing standard would allow companies to make vaccines for all countries and allow easier importation of vaccines in times of need. The WHO has formed a working group involving the FDA and others to discuss a uniform regulatory approach.

Other options to entice vaccine makers include tax credits for building or enlarging factories, liability protection and government subsidies that would pay a bonus to companies for every flu shot that finds its way to a citizen. That would encourage companies to market vaccines, something they don't now do.

Another suggestion being heard more often is the idea of guaranteeing the purchase of vaccine so companies can make extra doses without having to absorb the cost of what they still have in inventory at the end of the flu season.

''If you get a flu shot, and I meet you in an airplane, I'm happy because I'm less likely to get flu,'' says Sloan at Duke University. ''In that sense, it's a public health issue'' and should fall under the responsibility of government.

But it ultimately comes back to price. Vaccines have to be profitable enough for businesses to want to make them, even if some have to be tossed out every year.

''It's like turkeys at Thanksgiving,'' Sloan says. ''Some stores must throw away turkeys on Friday, but they make enough on the turkeys they sell, and they don't want to run out.

''We don't have that with flu vaccine.''

Support research

Another way to encourage manufacturers to enter the flu vaccine business, experts say, is to provide funding for research and clinical trials to test new vaccines and drugs. One way to judge high-level concern about flu, especially pandemic flu, can be seen in the increase in federal funding. The budget for flu research at the National Institutes of Health is projected to increase by 200% from 2001 to 2005.

That money will be spent in part on basic research into the flu virus itself, how it mutates and reproduces, and what makes one strain more dangerous than another, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Other areas of focus include new methods of manufacturing vaccines such as using non-egg-dependent cell cultures, reverse genetics and other new technologies.

One goal, he says, would be to see if the annual flu vaccine could be replaced by a ''perennial'' vaccine, one that would last a period of years, as most other vaccines do. That has not been possible so far, because the virus mutates so rapidly that a new vaccine needs to be created each year.

Research into new drugs to treat flu and new ways to diagnose it quickly are needed, Fauci says, along with studies on extending the existing vaccine supplies by giving smaller doses injected just under the skin rather than into muscle.

Given the chaos caused by this year's flu vaccine shortage and the likelihood of a flu pandemic in the future, Fauci says, ''it's clear we need to move toward next-generation influenza vaccines with all deliberate speed.'' Cover story

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