Vaccine in anthrax tests varied

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http://www.washtimes.com/upi-breaking/20041229-120334-6922r.htm

BioWar: Vaccine in anthrax tests varied

By Dee Ann Divis

Senior Science & Technology Editor

WASHINGTON, DC, Dec. 29 (UPI) -- The U.S. Food and Drug Administration, in

another step toward reopening a controversial military anthrax vaccination

program, will seek public comment within the next week on the vaccine

itself.

The FDA rule that will include public comment details the history of the

vaccine, including the Defense Department's involvement in its development

and the fact the vaccine proposed for use today is not the one actually used

in a key test.

The public comment period is required to lift an injunction issued on Oct.

27 by U.S. District Judge Emmett Sullivan, whose order halted a mandatory

Department of Defense vaccination program using the vaccine. Sullivan ruled

that FDA failed to follow its own procedures when it approved the drug. The

injunction was issued as the result of a lawsuit filed by opponents who

believe the vaccine is dangerous.

The vaccine -- Anthrax Vaccine Absorbed or AVA -- was developed over 25

years ago when drug approval rules were different. AVA and other old

formulations were later reviewed by FDA appointed panels to determine if

they met acceptable levels of safety and effectiveness.

AVA initially was approved based in significant measure on a test done years

ago among civilian textile workers at risk of infection from naturally

occurring anthrax. Critics said the test was limited and flawed and Sullivan

agreed that they had not been afforded adequate opportunity to raise their

objections.

The FDA's intent now is to approve the vaccine as safe. It has proposed a

rule entitled Biological Products; Bacterial Vaccines and Toxoids;

Implementation of Efficacy Review that contains that determination. The

docket number to file comments is 1980N-0208.

The document, posted on the FDA Web site before publication, describes the

history of the vaccine, including the intimate involvement of the military

in its development and testing.

FDA also reveals in the filing that, contrary to earlier reports, the

vaccine involved in the approval process and the vaccine actually used in

the initial test are not the same.

The current vaccine, once manufactured by the Michigan Department of Public

Health and now made by Bioport of Lansing, Mich., " is patterned after that

of Merck Sharp & Dohme with various minor production changes, " the FDA

noted.

The Merck vaccine was thought by the original FDA panel to be the one used

in the textile worker study.

" FDA has found, " the proposed rules states, " that contrary to the panel's

statement, the vaccine used in the (textile worker) study was not

manufactured by Merck Sharp & Dohme, but instead this initial version was

provided to Dr. Brachman by Dr. G. of Fort Detrick, U.S. Army, DoD. "

FDA goes on to conclude, however, that " DoD's continuous involvement with,

and intimate knowledge of, the formulation and manufacturing processes of

all of these versions of the anthrax vaccine provide a foundation for a

determination that the MDPH anthrax vaccine is comparable to the original

DoD vaccine. "

FDA asserts the three vaccines -- the Defense Department version, the early

Michigan version and the current version -- provide the same level of

protection based, in part, on tests on guinea pigs and rabbits.

The agency also contends comparisons of the Michigan vaccine and the Defense

Department vaccine show the level of safety is the same, though the agency

admits the data was " limited in the number of vaccines and samples

evaluated. "

FDA went on to say in the filing, " The serological responses to (the

Michigan vaccine) vaccine and the DoD vaccine were similar with respect to

peak antibody response and seroconversion. "

Antibody response and seroconversion are not, however, measures of safety,

said immunologist and scientist Craig Dees.

" The effectiveness is what is really being measured, " Dees told United Press

International. Dees is an expert on vaccine development and chief executive

officer of Provectus Pharmaceuticals.

Whether the vaccine also is effective against inhalation anthrax -- the

disease it primarily is being used to inoculate against -- also is at issue.

The conclusion that it is effective against inhalation anthrax is supported

by the textile worker study, FDA says in the filing.

The test, done in the early 1960s, involved 1,249 textile mill workers who

processed goat hair. Anthrax occurs naturally in sheep and goats and those

handling goat hair and wool are more likely to get infected, usually with

relatively less dangerous skin infections. The five people in the United

States who died of anthrax in the fall of 2001 had anthrax in their lungs

after inhaling finely powdered anthrax spores sent through the U.S. postal

system.

Among the mill workers, there were 26 cases of anthrax, five of which were

inhalation anthrax. Of those five, four were fatal. Three of those who

contracted anthrax had been vaccinated, though FDA says the vaccinations

were not complete.

The time period for the test was not given, though normally the number of

anthrax cases expected to occur among mill workers was 1.2 per 100 or

roughly 15 per year among the test group.

Because the vaccine appears to have protected workers against inhalation

anthrax, the suggestion was made the vaccine should be approved for that

use. A panel reviewing this test and others said there was not enough

information to make that judgment.

The FDA agreed there is not enough information for a determination on

inhalational anthrax, so it is suggesting no determination be made -- that

is nothing be put on the vaccine's label to indicate what type of anthrax

the vaccine is for.

The lack of a designation implies the vaccine is effective for inhalational

anthrax, an interpretation played up by representatives of current vaccine

maker Bioport and used to justify the use of the vaccine by the Defense

Department.

That's not necessarily wrong, Dees said.

" If I am immune to the cutaneous version it is very likely I'm immune to

inhalation also, " Dees said.

Dees also said a production process shift from using air to grow the vaccine

cultures (aerobic) to not using air (anaerobic) was not a significant change

and was likely done to improve the yield of the vaccine.

The changes in the different versions of the vaccine are important, Dr.

Meryl Nass, who opposes the vaccine's use, told UPI. Nass, an expert on the

vaccine, is based at Parkview Hospital in Brunswick, Maine.

" It is sort of like you take the (diphtheria, tetanus and pertussis) vaccine

and people complained that the pertussis part of it was causing side

effects, so it got changed from a whole cell to a spilt vaccine and the side

effects are completely different, " she told UPI. " The vaccine has half the

pertussis side effects of the old one but there are only these small

changes. You couldn't possible regulate them by calling them the same. "

Randi Airola

517-819-5926