A better shot

It is Allison Friend's job to make sure the legal eagles at Goodwin Procter are not grounded by the chills, sniffles, and hacking cough of the influenza season.

So, each year, the big Boston law firm purchases hundreds of flu shots and invites its attorneys to bare arms. But this year, Friend placed her order for vaccine in July, a good month earlier than in the past.

''It was so frustrating for people last year when there was a shortage of vaccine that it was at the top of our list this year to make sure we were shored up," Friend, the firm's chief human resources officer, said one morning last week. ''I actually had five partners e-mail me yesterday to ask if we're going to offer flu vaccine."

A year after an unprecedented -- and unexpected -- shortage of shots revealed significant problems in the way flu vaccine is produced and distributed, the makers and takers of inoculations have moved, sometimes modestly, to prevent a similar shortfall this flu season. Though signs are promising for this year, it's still unclear whether millions of doses of the vaccine will meet federal standards and be allowed on the market.

Last year, there were just two manufacturers of flu shots for the United States. This year, there are three, promising to produce up to 94 million doses (compared with last year's 61 million).

Last year, there were only limited initiatives to develop more efficient methods for making vaccine. This year, the federal government has poured tens of millions of dollars into the cause.

Last year, hospitals and health departments often relied on a single producer to provide them with vaccine, leaving them vulnerable when one company's entire stock was deemed unfit for human use. This year, those same health-care agencies have diversified, placing orders with several makers.

And one thing that has not changed since last year: The flu remains a lethal health threat, responsible for an estimated 36,000 deaths annually, principally among the elderly.

''You cannot predict flu severity or timing," said Dr. Carolyn Bridges, a medical epidemiologist in the immunization branch of the US Centers for Disease Control and Prevention. ''The best strategy is to be as prepared as you can for a severe season."

Those preparations could yield benefits beyond this flu season. If a highly lethal form of the flu became widespread -- as is feared will happen eventually with the avian flu now in birds in Asia -- having extra vaccine production capacity will be crucial.

Just a couple of decades ago, barely 12 million Americans a year received flu shots. But by the 1995 flu season, vaccinations soared to nearly 55 million, and in 2003, inoculations peaked at 83.1 million.

''It's a confluence of things happening," said Dr. Raymond Strikas, the CDC's associate director for adult immunization.

For one thing, public health authorities have embarked on aggressive campaigns encouraging flu vaccination. For another, Medicare, the federal health plan for the elderly, began in 1993 covering the $10 cost of shots. And then there were market forces: An industry evolved to provide inoculations in pharmacies, groceries, and offices.

The result: Demand for shots increased.

''It's grown every year," said Joanne Handy, president of the Visiting Nurse Association of Boston, which this year will give about 20,000 shots at retirement villages and at businesses, including Goodwin Procter. ''It only took a couple of bad flu seasons to have people realize the vaccine was really quite effective in preventing even worse outbreaks."

But making flu vaccine is a notoriously messy, chancy proposition requiring massive numbers of chicken eggs and a new recipe every year.

Between January and March, disease trackers, using virus surveillance reports from across the world, make their best educated guess at the flu strains likely to cause misery in the United States. Three viruses are identified, and work begins to brew a vaccine to ward off the germs.

To make vaccine, scientists need virus -- lots of virus. And eggs, it turns out, are one place where flu virus loves to grow. So bits of virus are injected into eggs, where they multiply and, later, are extracted, purified, and engineered so that they can't cause illness when made into a vaccine.

But here's the problem with using the egg technique: Making enough vaccine to provide protection for millions of Americans can take 10 months, egg supplies are unpredictable, and scientists never know for sure how much virus each egg can spawn.

That's why the federal government is spending $100 million on refining flu vaccine production. A significant chunk of that is being used to underwrite government-industry initiatives to develop approaches that avoid eggs and instead grow virus in animal cells, allowing for quicker, more reliable stocks.

''Eggs, God bless them, are a very, very good, time-honored way to make flu vaccine," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. ''But everyone realizes we need to make a transition from eggs."

If there was ever any doubt about that, it was erased almost precisely one year ago.

''Last year, everything was going fine and dandy and then on Oct. 5 -- boom! The roof fell in," said Dr. Walter Orenstein, former director of the National Immunization Program and now an Emory University vaccine specialist.

On that day, somber US health authorities gathered before the glare of TV cameras with a stunning announcement: Nearly half of the nation's expected allotment of flu shots would never make it to American shores. British regulators, alarmed by bacterial contamination at a Chiron Corp. factory in Liverpool, had halted production and prohibited shipment of about 50 million doses of vaccine.

The United States was left with a single supplier of flu shots, a company that now goes by the name of Sanofi Pasteur. The panicked elderly formed serpentine queues in the sun, waiting hours for shots. Vaccine was rationed. Profiteers attempted to sell shots for almost 10 times the usual sticker price.

While the shortage spawned considerable attention and concern, it was scarcely the first time there had been a dearth of shots against the flu or other infectious diseases.

The frequent supply interruptions reflect a collision of forces: economic, legal, scientific. Vaccines don't generate the kind of gargantuan profits produced by blockbuster drugs like Lipitor and Prozac, medicines that patients take every day to control cholesterol and depression. That makes vaccine less attractive to pharmaceutical companies. And they're more difficult to make than a pill.

Then there's the threat of legal action: Society is more willing to accept side effects from chemotherapy used to treat cancer than a shot given to a healthy person to prevent illness.

All of which helps explain how, by the autumn of 2004, only two companies made flu vaccine for the US market.

But this year, a third company has come into the fold: GlaxoSmithKline has pledged to make 8 million doses of flu vaccine, a decision driven by what a spokesman said was the company's recognition of a ''prime opportunity."

Dr. Colin Marchant, a vaccine specialist at Boston University School of Medicine, said that efforts to expand vaccination to even more adults and children could stimulate further interest by drug companies.

''GlaxoSmithKline coming in this year is an indication that this is a business manufacturers can get into and that can be attractive and can be more attractive if there's greater volume," Marchant said.

Sanofi Pasteur is expected to produce as many as 60 million shots, and Chiron has said its factory may yield 18 million to 26 million doses. It is still awaiting federal approval to ship its vaccine, expected in the next few weeks.

Because uncertainty remains about how much vaccine will be available, federal and state health agencies have recommended limiting who can get shots for another few weeks. Until Oct. 24, only the elderly, the very young, healthcare workers, and housemates of the chronically sick should be vaccinated.

But on that day, health authorities expect to make vaccine available to anyone who wants it. And that's the day Goodwin Procter already has booked to begin giving shots to its staff.

For more information about the flu, its symptoms, treatment and prevention, go to www.cdc.gov/flu. Stephen Smith can be reached at stsmith@globe.com.