Anticipated Supply of Flu Vaccine for U.S. Is Abruptly Cut in Half

U.S. public health officials warned Tuesday of serious flu vaccine shortages after the company that supplies half the nation’s flu shots said it couldn’t provide any vaccine this season.

Authorities urged healthy people to forgo their shots so more would be available for those most in need -- babies between 6 and 23 months, adults over 65, people with chronic illnesses and healthcare workers.

The warning came after British health authorities in effect shut down for three months a Chiron Corp. factory in Liverpool because of unspecified manufacturing problems. The plant makes Chiron’s entire supply of flu vaccine for the U.S.

Chiron, which is based in Emeryville, Calif., said the surprise closure of the facility meant that the company would be unable to ship vaccine before the flu season ended.

Chiron and French drug maker Aventis Pasteur are the only providers of flu shots to the U.S. A third company, MedImmune, makes an inhaled flu vaccine, but only about 1 million doses will be available, and this vaccine is not recommended for children or the elderly.

U.S. health officials were caught off guard. Health and Human Services Secretary Tommy G. Thompson said the shortage was “very disappointing news that creates a serious challenge to our flu vaccine supply.”

The decision by British authorities, Thompson said, came after an inspection of the Chiron plant late last week. U.S. officials were notified of the decision Tuesday morning, he said.

In California, the shortage means the state Department of Health Services won’t have the 573,500 doses of adult vaccine it ordered from Chiron. The agency has ordered 710,000 doses from Aventis Pasteur, and officials were scrambling Tuesday to locate more.

“This is going to be harsh on everybody,” said Dr. David Ramin, a Culver City doctor who administered 400 flu shots last year. “We’re going to have more people with influenza this year than any other year. This means more hospitalizations and more deaths from influenza than any other year.”

Jonathan Fielding, Los Angeles County’s public health director, said the shortage posed “a serious problem.”

Last year, the country administered 130,000 flu shots at its clinics for the poor, with the majority of the vaccine purchased from Chiron.

Fielding said that this year, the county had received a small amount of flu vaccine -- 15,000 doses -- from Aventis Pasteur and was on that company’s waiting list for more doses. “We’re not sure if we’ll get them,” he said.

According to the Centers for Disease Control, 5% to 20% of the U.S. population annually contracts influenza. In an average year, the disease is responsible for 200,000 hospitalizations and 36,000 deaths.

Chiron and Aventis had stepped up vaccine production this year because last year an early and hard flu season led to shortages. The companies had planned to deliver 100 million doses, nearly 20% more than last year’s flu season. Now just 54 million doses will be available.

Because it takes many months to manufacture flu shots -- a process that involves growing live virus in thousands of chicken eggs -- Aventis Pasteur can’t make up the shortfall. Aventis told government officials it can’t begin work on new vaccine until November, when its current orders are filled. The company has already shipped 30 million of the 54 million doses it plans to produce.

It is unlikely that vaccine supplies could be diverted to the U.S. from other parts of the world because any factories would have to be inspected and approved by the Food and Drug Administration, and those vaccines already are earmarked for other countries.

The shortage underscores the pitfalls of relying on just two manufacturers for flu vaccine, according to public health experts.

“This exposes the fragility of the vaccine supply in the United States,” said Neal Halsey, director of the Institute for Vaccine Safety at Johns Hopkins Bloomberg School of Public Health. “We should not have to depend on one or two manufacturers.”

Halsey said a better strategy was needed to maintain an adequate supply of vaccine and increase “our potential to deal with the possibility of a pandemic.”

CDC Director Julie Gerberding urged Americans not “to rush out and look for vaccine today,” but to wait and allow physicians, pharmacists and federal and state health officials to assess how much vaccine they have in hand, where it will be needed and by whom. “It’s not an emergency,” Gerberding said. “We’ll work through this.”

Although the population recommended to receive flu vaccine is about 180 million people, “we never vaccinate anywhere near” that many, Gerberding said. Subtracting those who probably wouldn’t seek a dose of vaccine anyway, she reckoned the “50-some million doses we have now will come close to meeting this demand.”

One bright spot is that the newest additions to the list of those recommended to get a flu shot -- children 6 and 23 months -- probably won’t have problems getting a dose of vaccine. Aventis Pasteur was the only producer of the flu vaccine formulation designed for babies.

Asked whether federal officials have the power to commandeer vaccine supply that has already been distributed to clinics, pharmacies, hospitals and physicians, Thompson said, “I don’t think that would be practical.”

However, CVS Corp., the nation’s second-largest drugstore chain, said Tuesday that because of the shortage it would be unable to offer flu shots at its stores this year. CVS said it was trying to determine how to make its supply of vaccine available to those most in need of it.

Chiron Chairman and Chief Executive Howard Pien said he learned of the British government’s actions at 3 a.m. from employees in Liverpool who had just received a letter from the Medicines and Healthcare Products Regulatory Agency, the British counterpart of the FDA.

The agency said it was suspending the factory’s license for three months for what Pien called “issues with systems and processes” at the factory. He said the actions by British regulators, who didn’t explain details for the license suspension, were “completely unexpected.”

“I cannot overemphasize how profoundly we regret that we will be unable to meet the public health needs this season,” Pien said.

Chiron’s troubles began in August when it announced it needed to destroy 4 million doses of vaccine that were contaminated with a bacterium called serratia. Chiron said it was delaying shipment of all other flu vaccine until it learned how the contamination occurred.

Pien said Chiron concluded that human error was to blame and that the remaining batches of vaccine were safe. It planned to begin shipping vaccine this month, he said.

As recently as last Tuesday, Pien told the Senate Special Committee on Aging that his company expected to begin delivering 46 million to 48 million doses of flu virus to the U.S. market in early October. He told the committee that the shipment of an additional 2 million doses to a U.S. government stockpile also was on schedule.

CDC Director Gerberding said U.S. officials “had been optimistic” that Chiron had isolated the contamination of flu vaccine to a batch of some 6 million to 8 million doses. In recent months, according to U.S. officials, the FDA was relying primarily on Chiron’s analysis of the cause of contamination and its assessment that it was limited.

In late summer, said Jesse Goodman of the FDA, an inspection team visited Chiron’s facility for other purposes and made some additional inspections in light of the flu vaccine contamination reports.

“We were waiting for a complete analysis of the situation to be forwarded to us at FDA and then we would respond to that appropriately,” Goodman said Tuesday. In their communications with U.S. regulators, Goodman said, Chiron executives reported “they believed they had isolated the cause of the problem and the affected lots.”

However, Pien said British regulators inspected the plant and found fault with the company’s manufacturing “system and process.” Pien did not provide details on what the British inspectors found.

“I think this reflects a regulatory philosophy that it is not just the end product that a supplier can say is safe,” he said.

Pien said the company expected to begin talks with British regulators today. However, he held out little hope that the matter would be resolved in time for this year’s flu season, and said he believed that British regulators had final authority over the plant.

“I think it is reasonable to assume that the vaccine we had hoped to supply to the U.S. is gone,” he said.

Thompson, however, noted that British regulators have jurisdiction only over Chiron-produced flu vaccine destined for the British market; Chiron supplies about 1 in 5 doses of flu vaccine received by Britons.

Goodman said the FDA team would be asking “why it was necessary to suspend their license” to manufacture, and “why it was necessary to go beyond the 6 to 8 million doses” initially identified as contaminated.

Asked whether any of Chiron vaccine might be found safe for use in the U.S., Thompson said, “we can’t say at this time.”

Chiron, a small biotechnology company, entered the flu vaccine market in 2003 with its $878-million acquisition of PowderJect Pharmaceuticals. Chiron sold its entire supply of 38 million doses last year, adding $245 million to its revenue. The shots quickly became its biggest product.

Pien emphasized that Chiron remained committed to the flu vaccine business and was in the process of investing $100 million to improve the Liverpool factory. The company also was developing a faster method of producing flu vaccine that does not use chicken eggs.

The company said Tuesday that its earnings for 2004 would be one-quarter of what it had forecast just last month. Its shares closed at $37.98, down $7.44, or 16%, on Nasdaq.

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Times staff writers Myron Levin and Jia-Rui Chong contributed to this report.

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(BEGIN TEXT OF INFOBOX)

Some Facts About This Year’s Influenza Vaccine

Here are answers to some basic questions about the flu vaccine:

Question: Why can’t some other company besides Chiron make more vaccine?

Answer: Vaccine production takes several months, starting with growing the vaccine strain of the virus in chicken eggs and ending with vials of vaccine that must pass an array of federal safety tests before they can be used. The other major vaccine maker, Aventis Pasteur, reports that it’s already operating at full capacity and can’t make more until after November, once existing orders have been filled.

Q: What about diluting the vaccine to get more shots from each dose?

A: Officials are discussing that possibility, but it isn’t known yet if that would be a safe or effective option.

Q: Who should get a shot this year?

A: Children 6 to 23 months old, people 65 and older, people with underlying or chronic medical problems, pregnant women, nursing home residents, healthcare workers who directly care for people at high risk of flu complications, child care workers who take care of children under age 2 and children who regularly take aspirin.

Q: What if I want the vaccine and I’m not in this group?

A: Officials are asking healthy people not to seek shots this year so enough are available for those who need them most.

Q: Will that inhaled flu vaccine be available and is it safe?

A: About 1.1 million doses of MedImmune Inc.’s FluMist will be available for healthy 5-to-49-year-olds and even healthcare workers. It’s made from live but weakened influenza virus, and experts say it is not necessary for people who get it to be quarantined for a week to keep from spreading it to others.

Q: How bad will the shortage be?

A: From 90 million to 120 million Americans are at high risk of complications from the flu or have close contact with people who are, but not that many get shots each year. Last year, more than 80 million got shots -- a record high. Typically, 50 million to 80 million do each year.

Q: What else can I do if I can’t get the vaccine?

A: People may want to discuss with their doctors getting a prescription for one of the antiviral drugs that can lessen the severity of flu if taken right after symptoms begin.

From Associated Press