Find A Flu Shot

Companies Look Past Chicken Egg
To Produce Flu Vaccine

By BETSY MCKAY and MARILYN CHASE
Staff Reporters of THE WALL STREET JOURNAL
October 12, 2004; Page B1

Flu-vaccine makers, concerned that growing demand for shots will outstrip the 60-year-old method of producing vaccine in chicken eggs, are racing to implement new techniques. But it could be several years before modernized flu vaccines become available in the U.S.

Flu shots are produced by injecting influenza viruses into the embryos of millions of eggs, which are incubated, harvested and then blended into vaccine. Complicated and labor-intensive, the months-long process makes it impossible to create more vaccine in the event of a sudden shortage -- like the one triggered by last week's shutdown of a Chiron Corp. plant in England.

Now, Chiron, France's Aventis Pasteur, a unit of Sanofi-Aventis SA, and other drug and biotech companies are trying to diversify their egg-based vaccine production by using cell tissue from humans or animals. Chiron, the Emeryville, Calif., company whose egg-based production facility in Liverpool had its license revoked by British regulators, is developing a means of growing vaccine using cell lines produced from the kidney of a dog. Aventis, the sole remaining supplier of flu vaccine to the U.S., is testing a method developed by a Dutch company that uses a cell from a human retina. Baxter International Inc. plans to enter the market with a flu vaccine produced using cells from African green monkeys.

New cell-culture methods, which rely on genetic engineering, already are used to make smallpox vaccine, but they still haven't been fully proved for flu-vaccine production. The new methods hold out the promise of greater efficiency, and possibly more profits, than the old-fashioned chicken-egg method. And they could allow vaccine makers to churn out more shots on shorter notice. That's a big problem with the flu vaccine, whose demand is difficult to predict because taking the shots is largely voluntary.

Only one or two flu shots can be produced from a chicken egg; in contrast, cell tissue is genetically engineered to replicate, making it possible to grow infinite amounts of virus. Compounding the lead time needed with chicken eggs, vaccine producers must sign contracts with farmers six months before vaccine production can begin. The farmers raise hens to lay eggs of a specific eggshell-thickness and other characteristics.

With cell-culture technology, "cells are stored in the freezer, you take them out anytime you want, and you don't have to depend upon ... breeders to get their stocks to you," says James Young, president of research and development for MedImmune Inc., the Gaithersburg, Md., maker of FluMist nasal-spray vaccine, which is produced with eggs.

It isn't just the loss of nearly half of the U.S. flu-shot supply that is pressuring flu-vaccine makers to devise faster production methods. A growing number of cases in Asia of deadly avian flu has experts worried that a pandemic, or a strain to which humans have no immunity, could erupt. Thirty people have died in Thailand and Vietnam this year from the disease.

In case of a pandemic, vaccine makers would be racing to develop and produce enough new vaccine to inoculate millions of people before the deadly disease reached them. Ronald Brus, chief executive of Crucell NV, the Dutch firm in a joint venture with Aventis, says the versatility of using human cells "could allow you to grow virus strains that are currently very tough to grow on embryonated eggs."

Still, cell-culture technology isn't likely to replace chicken eggs completely. Despite the drawbacks, the egg method is widely considered safe and reliable. The federal government is steering $50 million this year to improving flu-vaccine production. The money is being split between securing a steadier supply of eggs for manufacturers and encouraging new techniques. "This is not an effort to shift from eggs to new technology," says Bruce Gellin, director of the Health and Human Services Department's National Vaccine Program Office.

The newest flu vaccines probably won't be approved by the Food and Drug Administration for at least three years, since most still are being developed or tested. "Tissue culture is considered a new product, and you have to go through a complete set of clinical trials to prove the vaccine is safe and efficacious," says Robert Belshe, director of St. Louis University's Center for Vaccine Development.

Michel De Wilde, executive vice president for research and development at Aventis, says the cell-culture method being worked on with Crucell could eventually replace egg-based production "if it fulfills all its promises." To achieve that, though, will take clinical testing and enough production capacity to churn out millions of doses. Making flu vaccine with the cell-based technology is "many years away," Mr. De Wilde says.

In the meantime, Aventis is considering further investments to improve its egg-based production, including expanding output and securing a year-round supply of eggs.

Baxter International, based in Deerfield, Ill., says it is "scaling up and validating" a plant in the Czech Republic, where it also plans to produce a flu vaccine using the same cell-culture technology it used to produce a smallpox vaccine stockpile, a spokeswoman says. The technology is based on vero cells, a cell line originally derived from African green monkeys. The company expects to launch the new flu vaccine in Europe in late 2005 or early 2006 and to begin seeking approval in the U.S. at about the same time.

A flu vaccine made from Chiron's cell-culture method is entering phase III studies of effectiveness in Europe. (Phase III studies are the large-scale, definitive studies of effectiveness and safety that companies use in seeking marketing approval.) Chiron has filed an application with the FDA to begin studies on its cell-culture vaccine in the U.S., a spokeswoman says.

Dr. Young, MedImmune's research and development chief, says any shift away from egg-based production of flu vaccine won't be easy despite the advantages of using cell cultures. "The whole industry has been built up around egg-based production," he says. "To switch to cell culture is a massive effort." Eggs also have been highly productive for vaccines because birds are susceptible to most flu viruses. "The viruses grow well in their eggs," Dr. Young says.

Trying to stand in a 2 hour line right now does not appeal to me.

Vendors overcharging for flu vaccine

Survey: Some distributors offer U.S. hospitals flu vaccine at up to 10 times the original price.
October 13, 2004: 7:15 PM EDT



NEW YORK (CNN/Money) - U.S. hospitals have been actively solicited by pharmaceutical distributors offering the flu vaccine at vastly inflated prices, since the supply has been cut in half due to Chiron Corp.'s plant contamination problems, a survey said Wednesday.

"This is a public health crisis," he said. "The bottom line is people are going to die, if they don't get this vaccine. It's the most vulnerable -- the elderly, the sickest of the sick and children -- who need this vaccine. It (price-gouging) is just a despicable practice."

Matrix--

Seattle is miles away--and a different climate zone.