De Leon Defers To FDA On Legality Of DOD's Anthrax Vaccine Program

by Elaine Grossman

Inside The Pentagon

May 11, 2000

Deputy Defense Secretary Rudy de Leon told reporters late last month that although two Air Force Reserve attorneys had challenged the legality of the Defense Department's anthrax vaccination program, the Pentagon leadership retains faith in the Food and Drug administration's determination of the controversial vaccine's effectiveness against an inhaled anthrax threat.

"FDA is the preeminent organization in America -- perhaps in the world -- in terms of the safety of medicines and vaccines," de Leon said at an April 26 breakfast with print journalists. "I think the department is content to go with their record in terms of the safety and effectiveness of the vaccine."

A week prior to de Leon's comments, two judge advocates general from the Air Force Reserve -- acting on their own and without the imprimatur of their service -- issued a memorandum concluding it is illegal for the U.S. military to order individuals to submit to the anthrax vaccine because FDA has never legally certified its, use against an inhaled form of anthrax (Inside the Pentagon, April 20, p1). Defense officials believe a threat to U.S. military personnel would come in the form of a weapon that dispenses anthrax spores, which individuals would breathe in the air.

Yet, the two JAGs state, the FDA-approved label for the anthrax vaccine alludes only to protection against anthrax that is contracted through the skin. When the Defense Department sought to launch its immunization program, DOD's assistant secretary of defense for health affairs sought from FDA a determination on whether the approved vaccine could be used against an inhaled threat.

In March 1997, Dr. Michael Friedman, FDA's lead deputy commissioner, told DOD such a use is "not inconsistent with the current label" (ITP, Feb. 17, p1). Although the Pentagon and FDA cite Friedman's statement as the primary FDA approval upon which the Defense Department program is legally based, the two JAGs say the letter failed to meet the legal standards for an FDA decision that can affect the status of the vaccine. They cite a still-pending application submitted to FDA in 1996 by Michigan Biologic Products Institute (MBPI), then the anthrax vaccine manufacturer, seeking approval for investigational use of the vaccine against an inhaled threat. (MBPI was subsequently bought by BioPort, which currently is the sole-source supplier of the anthrax vaccine.)

MBPI's application for "investigational new drug" status for the anthrax vaccine, portions of which were obtained by Inside the Pentagon, state clearly that one of the investigational "indications" the manufacturer sought to pursue was use of the product for immunization against "inhalation anthrax."

Lacking a formal FDA decision on that application for an investigational status or an approval letter that comports with laws and regulations, the anthrax vaccine remains an IND if it is used against an inhaled threat, the JAGs argue.

DOD also cites a letter sent to Congress by FDA Associate Commissioner Melinda Plaisier on Nov. 26, 1999, stating, "There is presently no basis for concluding that the anthrax vaccine, a licensed product, when used in accordance with current labeling, should be used pursuant to an IND application" or placed into an IND status.

But critics of the program hold Plaisier's letter merely begged the question of whether the label accounts for the vaccine's use against an inhaled form of anthrax.

The drug company's IND application followed substantial discussion within the Army scientific and medical community about the need for such special approval to use the existing vaccine against inhaled anthrax -- something regarded as a new medical "indication" for the product. Notes from a meeting held Oct. 20, 1995, at the Army's Joint Program Office for Biological Defense show DOD and industry officials discussed the need for a possible expansion of the licensed anthrax vaccine "to include protection against an aerosol challenge of spores."

Drugs or biologic products in an IND status can be administered only to individuals who give their "informed consent." Defense Department leaders do not regard the anthrax vaccine as an IND, and thus they have pursued a program in which DOD gives the vaccine on a mandatory basis to service members. To date, more than 400,000 military personnel have taken one or more shots in the six-vaccine regime, which requires annual boosters after that. The Pentagon intends to vaccinate the entire military against anthrax by 2005.

De Leon said he had read about the JAGs' challenge to the program's legality and "was interested in their comments."

But he said the Defense Department -- including its surgeons general -- "are really willing to accept the independent judgment of FDA on this question. I think their credentials and bona fides are clear going back to their creation by Theodore Roosevelt after he read the Upton Sinclair book, 'The Jungle,' back at the turn of the century.

"So I think FDA has said that this is an approved vaccine," he added.

One Air Force judge advocate general, speaking "on background" with ITP this week, said, "Like the FDA letter [from Friedman], that response is semantically correct. It is an approved vaccine for the purposes for which it is labeled. However, the producer apparently believed the vaccine was not licensed for inhalation anthrax, as indicated by its currently pending application."

Jim Turner, a Pentagon spokesman, told ITP this week FDA has indeed specifically approved the Defense Department's use of the anthrax vaccine to protect against an inhaled threat. "The anthrax vaccine is approved for use by the Food and Drug Administration; it is not an investigational new drug under FDA rules, nor is it being used by DOD under terms that subject it to IND rules.

"The agency authorized to make determinations on whether a drug is being used under terms that make it subject to IND regulations is the Food and Drug Administration," Turner continued. "The FDA has determined that the anthrax vaccine as used by DOD in the Anthrax Vaccine Immunization Program is not an investigational new drug, but is an approved drug being used in accordance with its approved label. . . . DOD and FDA interpretations of the approved anthrax vaccine label encompass use for inhalation or cutaneous exposure."

In fact the label notes the product offers protection against anthrax for veterinarians, laboratory workers, or anyone coming into contact with potentially infected animal hides or other products. The route of exposure for these kinds of workers has principally been cutaneous, or through the skin, but the label does not overtly specify.

Turner said under the 1996 IND application, MBPI sought to get a change in the label to "specifically list inhalation exposure as a labeled indication. This IND application in no way suggests that DOD believed the approved label did not already encompass inhalation exposure under the normal, six subcutaneous shot schedule." He said Friedman's 1997 letter "eliminated any remaining doubt on the interpretation of the label."

An Air Force JAG responded last week the Defense Department's "assessment of the IND process is not borne out by the documents themselves -- the IND application and the Army [meeting] minutes -- which indicate MBPI was looking at getting an indication on the label for aerosolized anthrax."

Concerning the JAGs' allegation that FDA has not, to date, offered a legally binding certification on this specific use, Turner said, "Although such a distinction might be relevant in an FDA-initiated legal enforcement action, it is nonsense to suggest that the FDA has not made its decision."