".....The FDA has been
criticized for being too cozy with the pharmaceutical industry and for
failing to guarantee drug safety by not disclosing its knowledge of side
effects from medications for arthritis and depression......."

http://www.***.com/ ,1413,87~11268~2458634,00...
San Mateo County Times

Flu shot production system uncertain
By COX NEWS SERVICE

Sunday, October 10, 2004 - ATLANTA -- The sudden, major flu vaccine shortage
that shocked health authorities last week highlights two vulnerabilities in
the nation's immunization system: a reliance on a few private manufacturers
that use old technology, and government's faith that companies will make
safe products and quickly report problems.

Insiders, who have long warned the fragile system needs reforms, say it
could prove even more catastrophic if bird flu sweeps the globe or
bioterrorists hit.

Since the 1970s, the number of companies making all vaccines has dwindled
from 25 to five, even as the types of vaccines have doubled. Vaccines
against six diseases now have a single manufacturer, causing shortages
whenever the companies encounter snags.

The cooking.net">food and Drug Administration, which oversees the vaccine industry in the
United States, relies on companies to come clean about most problems. But
even though Chiron Corp. revealed contamination at its plant in England in
August -- and the company started investigating deeper concerns in
mid-September -- FDA officials admitted being caught off guard Tuesday when
British authorities suspended all production. Chiron is one of two suppliers
of U.S. flu vaccine.

The United States is on the brink of flu season with only half its 100
million doses of vaccine now expected, forcing health officials to call for
voluntary rationing so that people at highest risk can be protected. Reports
of price gouging of as much as tenfold have begun.

The dire situation is just a warm-up for what scientists really fear: a flu
pandemic, likely to be caused by bird flu, or avian influenza, which has
appeared again this fall in Southeast Asia. Such an outbreak could kill
millions across the globe; a flu pandemic in 1918 killed at least 20 million
people worldwide, including half a million Americans.

Researchers are scrambling to develop a bird flu vaccine, but a proven one
does not exist. Chiron is among the companies working on that vaccine.

"If we had widespread disease at the level of a pandemic, we'd be in a lot
more trouble, now that we understand how fragile the supply and distribution
system is," said Dr. Gregory Poland of the Mayo Clinic in Rochester, Minn.,
a vaccine adviser to the Centers for Disease Control and Prevention in
Atlanta.

Ordinary flu causes 36,000 deaths and more than 200,000 hospitalizations
each year, mostly among the elderly, the CDC says.

Since vaccines, unlike most {*filter*}, prevent disease instead of treating it,
regulators -- and trial lawyers -- tolerate few side effects. Companies must
perform large clinical trials, which can cost $200 million, to demonstrate
safety.

And they face a market subject to the whims of a public that demands cheap
immunizations but is often lax about getting the $20 shots. After 12 million
doses of flu vaccine went unused two years ago, the manufacturers had to
dump them and swallow the losses, leading one company, Wyeth, to get out of
the flu shot business.

"We set the safety bar very high and squeeze out companies by forcing low
prices," said Dr. Paul Offit of Children's Hospital of Philadelphia, who is
writing a book about the vaccine industry. "We have this myth of
invulnerability. We don't think (a disease) is going to affect us until it
hits us."

In just the past four years, the country has dealt with nine shortages of
six vaccines, including the swift depletion of last year's 87 million doses
of flu vaccine after influenza struck early and hard.

Experts have proposed systematic solutions -- tax incentives, government
subsidies, insurance coverage mandates, vaccine vouchers for the poor and
guarantees of buying back leftover doses. Others want to see the government
take over vaccine production entirely.

But the proposals, particularly those calling for government buybacks, have
gotten little traction, perhaps because paying for wasted vaccine would
generate political heat.

"How do you survive the congressional hearings if you're tossing out 10
million doses each year and (government is) paying for them?" asked Dr. Walt
Orenstein, former director of the CDC's National Immunization Program and
now associate director of the Emory Vaccine Center.

"All of the steps are likely to have substantial cost implications. Are we
as a society willing to pay for them?"

Not enough disclosure

Along with the manufacturing vulnerabilities is the question of whether the
FDA scrutinizes drug manufacturing closely enough. The FDA has been
criticized for being too cozy with the pharmaceutical industry and for
failing to guarantee drug safety by not disclosing its knowledge of side
effects from medications for arthritis and depression.

Merck & Co., the maker of Vioxx, pulled the popular arthritis drug from the
market last week after a study found it increases the risk of heart attack
and stroke -- findings that had been suggested in earlier research. And
after months of controversy, an FDA panel recently said the antidepressant
Paxil should carry a warning about the possibility it causes suicide in
children. Some FDA scientists were aware of the danger for many months,
critics say.

Several members of Congress accused the FDA of suppressing information last
month in a hearing about Paxil and other antide- pressants.

"There is something terribly rotten at the FDA," said Rep. Peter Deutsch
(D-Fla.). "No agency charged with protecting public health should have
behaved with such indifference."

That the FDA didn't realize the full extent of Chiron's vaccine problems
until Tuesday and may not have exercised the same level of safety concerns
as its British counterpart is also troubling to some.

"I say thank God that the British made their decision and kept possibly
contaminated products off the market," said Barbara Loe Fisher, director of
the National Vaccine Information Center in Vienna, Va.

The vaccine industry's financial struggles are compounded by technological
issues -- especially with flu vaccine, which uses a 50-year-old
manufacturing system involving chicken eggs and guesswork that takes half a
year to complete.

Each February, health officials select the three strains expected to
circulate most the next flu season. Companies use "seed strains" to grow
vaccine in eggs, which takes months. In late summer, they combine the three
strains into one product, testing it for safety before delivery in early
fall.

"If something goes wrong, like now, late in the process, it becomes very
difficult to re-gear up the process," said Dr. Anthony Fauci, head of
infectious diseases at the National Institutes of Health.

Researchers are studying two improvements: growing vaccine in kidney cells
from dogs or monkeys instead of in eggs, and genetically engineering flu
strains.

Vaccines grown in animal cell lines, like the polio vaccine, can be produced
at almost any time because companies don't have to wait for a fresh supply
of eggs, said Dr. Robert Webster, a flu expert at St. Jude Children's
Research Hospital in Memphis, Tenn.

In another approach, "reverse genetics," scientists are assembling the exact
bits of virus desired for a flu vaccine, instead of mixing viruses and
hoping they form the intended combination.

Webster has used reverse genetics to develop an experimental bird flu
vaccine. It, along with candidate vaccines from the CDC and a lab in London,
will soon enter clinical trials.

Congress appropriated $50 million this year for these vaccine developments
and for more eggs. The Department of Health and Human Services has asked for
$100 million for next year.

Previous vaccine shortages have sparked calls for reform that soon faded. A
silver lining of the new vaccine emergency is that this time, the heightened
attention could have staying power.

"This is the most significant shortage we have ever had," said Emory's
Orenstein. "This time the pressure needs to stay on."

Added Webster: "It's a {*filter*}y disaster . . . that the most affluent and
scientifically advanced country in the world can't make our own vaccine.
We'd better listen to this wake-up call."

David Wahlberg and Charles Seabrook write for The Atlanta
Journal-Constitution. E-mail: dwahlberg(at)ajc.com; cseabrook(at)ajc.com