DOD Needs More Anthrax Vaccine By July To Keep Program On Track

by Keith J. Costa

Inside The Pentagon

March 30, 2000

The Defense Department needs Food and Drug Administration approval to release
at least one additional lot of anthrax vaccine by July in order to continue
administering shots on schedule for phase one of the Pentagon's mandatory
anthrax vaccination
effort, according to Army Col. Randy Randolph, director of the Anthrax
Vaccine Immunization Program agency.

Deviating from the schedule approved by FDA for anthrax vaccines could
further erode confidence in the controversial program among lawmakers and
service members, perhaps beyond those who have expressed concern that the
vaccine is unsafe. DOD officials adamantly defend the vaccine as both safe
and effective.

In a February 1997 memo, the director of FDA's vaccine division argued that
DOD should obtain the "informed consent" of all recipients in the
immunization effort if the military is unable to adhere to the shot schedule
(Inside the Pentagon, Feb. 24, p1).

The Pentagon has just over 350,000 doses of FDA-approved anthrax vaccine in
its stockpile and is using 75,000 doses a month -- enough to last until July.
DOD is awaiting FDA approval of five vaccine lots purchased by DOD from the
state of
Michigan, which owned the nation's sole licensed anthrax vaccine production
plant until September 1998, Randolph told ITP March 29. An average lot of
vaccine contains 200,000 doses. FDA is reviewing test data for the five lots
-- Nos. 21, 39, 40,
42 and 45 -- to assess the potency, purity, safety and sterility of the
vaccine. The AVIP agency expects to discuss the status of those lots with FDA
by the first week of April, Randolph said.

The Pentagon also requires the release of three of those lots to continue
phase one of the vaccination program as planned for the rest of the year.
Phase one involves administering anthrax vaccine to service members and some
civilians already assigned to high-threat areas like Korea or the Persian
Gulf, or deploying to those
areas.

The three lots are expected to keep phase one on track until the present
owner of the anthrax vaccine production plant, Lansing, MI-based BioPort,
secures an amended license from FDA to make the vaccine. Defense Secretary
William Cohen will not allow the use of BioPort-produced vaccine until it
obtains the license, according to DOD leaders.

The BioPort facility has been completely renovated. But a November 1999
inspection found numerous problems associated with validating the process for
making the drug that have to be resolved before FDA approves the company's
license application. FDA and company officials have been meeting regularly to
settle outstanding issues related to the license application.

In December 1999, Assistant Secretary of Defense for Health Affairs Sue
Bailey announced that DOD will delay implementation of the anthrax program's
second phase, which calls for immunizing early deploying forces into
high-threat areas
(ITP, Dec. 16, 1999, p1).

"We will not launch phase-two vaccinations until we and the FDA are
completely satisfied that the BioPort plant meets the highest possible safety
standards," she said at a Dec. 23 press briefing. "It is difficult to
estimate precisely how long . . . this will take, but it could be in the
range of six to 12 months."

Randolph expressed confidence that FDA will approve the release of at least
one or two vaccine lots in July, and the BioPort amended license request by
early next year, thereby avoiding any delays in administering shots to phase
one recipients. Up to
415,000 people have received anthrax vaccine shots for the phase-one effort.

Randolph said the figure "includes people who are somewhere in the middle of
the dosing schedule and will need their next dose on time, and people we're
starting . . . with the vaccine program because they've just received orders
to be reassigned to
Korea or Southwest Asia, or their unit is being deployed to the high threat
areas for training."

For "primary immunization," the FDA package insert for the vaccine recommends
administering three shots, two weeks apart, followed by three more injections
given at six, 12 and 18 months. Those in the program should receive a booster
shot every
year thereafter to maintain immunity, the insert states.

If FDA is unable to release additional anthrax vaccine by July, the AVIP
office will have to deviate from the FDA-approved dosing schedule. "We will
resume administering shots when more vaccine comes in, starting up again
where we left off,"
Randolph said.

The Pentagon is conducting "contingency planning" in case the DOD vaccine
stockpile runs dry, he said. However, DOD officials have yet to discuss
proposed contingency plans with their FDA counterparts. "It's a little bit
premature . . . [but] I
believe we would consult with FDA if problems arise" with maintaining the
stockpile, he added.

DOD policy mandates immunizing service members and certain civilians
according to the FDA-approved shot regimen. Deviations from that schedule are
to be the exception and not the rule, according to a Sept. 11, 1999,
memorandum from
Bailey to the service secretaries.

"Deviation from this schedule should . . . be documented by bonafide reasons
such as pregnancy, active infection, etc. Although the effect of specific
deviations from this schedule on the efficacy of the vaccine is unknown, in
general, the greater the deviation the less certain the protective effect in
humans," the memorandum states.

DOD policy also states that if a person is given at least one vaccine dose,
and there is a delay of less than two years in administering the next one,
that person need not restart the entire shot series from the beginning.

"For the anthrax vaccine, this approach is supported by unpublished data in
humans that shows a robust antibody response to the anthrax vaccine one to
two years after a partially completed primary series," according to the
memorandum. Randolph
stressed that, medically speaking, extending the length of time between shots
will simply delay the body's immune response, with no adverse health effects.

"That stands to reason," he said. "If you get [your next shot] two months
later, you're not going to get an immune response until two months later."
Randolph stressed that the AVIP office closely monitors when personnel
receive injections and has found
the vast majority of service members who have participated in the phase-one
program have received their shots within a "minus-one- to plus-seven-day
window" of their due date.

DOD officials do not need FDA's blessing to go "off-label" in deviating from
the approved shot schedule, according to Pentagon and FDA officials. FDA can
regulate the manufacture of vaccines but not the practice of medicine,
Randolph said.

Nonetheless, a vaccine supply shortage and subsequent deviations from the
shot schedule will raise the ire of the AVIP's congressional critics. Going
"off-label" -- even temporarily -- may undermine the credibility of the
program, which depends on strictly adhering to FDA guidelines. Moreover, some
observers say the health effects of doing so are not well understood.

Key FDA officials have already expressed concerns about DOD deviating from
the FDA-approved shot schedule. In a Sept. 29, 1999, letter to Bailey,
Kathryn Zoon, director of FDA's Center for Biologics Evaluation and Research,
wrote: "This schedule is the only regimen shown to be effective in protecting
humans against anthrax and is the only schedule approved by FDA. . . . We are
unaware of any data demonstrating that any deviation from the approved
intervals of doses found in the approved labeling will provide protection
from anthrax infection."