State Department: Serious Problems in the Anthrax Vaccine Immunization
Program (Letter Report, 12/13/2000, GAO/GAO-01-21).

In 1998, the State Department stockpiled anthrax vaccine and antibiotics
at several diplomatic posts near Iraq. In the event of an anthrax attack
by Iraq, this stockpile was to be used for post-exposure immunization
and treatment. In 1999, the State announced that it was starting a
voluntary Anthrax Immunization Program for U.S. government employees,
their dependents, and other personnel serving overseas. According to the
Food and Drug Administration (FDA), full pre-exposure protection from
anthrax requires six vaccinations given over an 18-month period,
followed by an annual booster. Because there were insufficient supplies
of vaccines approved by the FDA, State decided to suspend plans to
expand the program beyond the pilot site until more vaccine was
available. GAO found that both the State Department's prepositioning of
anthrax vaccine at diplomatic missions and the voluntary anthrax
immunization program have been poorly implemented. Specifically, the
vaccine was not properly stored or refrigerated, requirements for the
voluntary program were not accurately estimated, and surveillance
procedures used in the pilot program to monitor reactions to the vaccine
were inadequate.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  GAO-01-21
     TITLE:  State Department: Serious Problems in the Anthrax Vaccine
	     Immunization Program
      DATE:  12/13/2000
   SUBJECT:  Immunization services
	     Terrorism
	     Embassies
	     Immunization programs
	     Biological warfare
	     Americans employed abroad
	     Military intelligence
IDENTIFIER:  Dept. of State Anthrax Vaccine Immunization Program
	     CDC/FDA Vaccine Adverse Events Reporting System

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GAO-01-21

Report to Congressional Requesters

December 2000 STATE DEPARTMENT Serious Problems in the Anthrax Vaccine
Immunization Program

GAO- 01- 21

Lett er

December 13, 2000 The Honorable Jesse A. Helms Chairman, Committee on
Foreign Relations United States Senate

The Honorable Benjamin A. Gilman Chairman, Committee on International
Relations House of Representatives

The Honorable Walter B. Jones House of Representatives

In the spring of 1998, the Department of State stockpiled anthrax vaccine
and antibiotics at a number of its diplomatic posts located within SCUD
ballistic missile range of Iraq. According to the State Department, these
supplies were stockpiled with the intent to administer post- exposure
immunization and antibiotic treatment following any possible anthrax attack
by Iraq. The State Department purchased and received 8,000 doses of anthrax
vaccine from the Department of Defense in May 1998, which it distributed to
eight U. S. diplomatic posts.

One year later, in May 1999, the State Department announced that it was
instituting a voluntary, worldwide Anthrax Vaccine Immunization Program for
eligible U. S. government employees, their families, and other personnel
serving abroad. First, a pilot project was started in October 1999 at a U.
S. mission in the Persian Gulf area. 1 Using the experience from the pilot
project, the program was to be gradually expanded to posts that State
believed could be the target of an Iraqi biological attack; then to posts in
40 countries that State has identified as at critical, high, or medium risks
to terrorist attack; and finally, to all posts worldwide. According to the
Food and Drug Administration, full pre- exposure protection from anthrax
requires a series of six anthrax vaccine immunizations given over an 18-
month period, followed by an annual booster. Due to the insufficient supply
of anthrax vaccine approved by the Food and Drug Administration, the State
Department announced in September 2000 that its plans to

1 According to the State Department, the locations of U. S. missions where
the anthrax vaccine was stockpiled and where the pilot program was conducted
are sensitive and cannot be identified in this report.

expand the program beyond the pilot site were suspended until more vaccine
is available.

You asked us to review the State Department efforts to administer anthrax
vaccine at U. S diplomatic missions overseas through the contingency
stockpiling of vaccine at U. S. diplomatic missions for post- exposure
administration and the voluntary Anthrax Vaccine Immunization program.
Specifically, you requested that we (1) discuss the rationale for the State
Department's decision to establish a voluntary anthrax vaccine immunization
policy and (2) examine how well the stockpiling of vaccine at diplomatic
posts and the voluntary anthrax immunization program have been implemented
to date.

Results in Brief The State Department established a voluntary anthrax
vaccine immunization policy for its employees and their dependents based on
its

interpretation of an intelligence assessment that U. S. diplomatic and
consular establishments abroad are threatened by potential biological and
chemical attack. According to intelligence analysts involved in the
assessment, however, the assessment was an extremely limited and general
assessment that did not evaluate the relative risks of chemical and
biological attack on U. S. missions overseas, identify the chemical and
biological agents likely to be used, or assess the ability of states or
terrorist groups to disperse chemical or biological agents and cause
casualties. Diplomatic Security officials in the State Department and
Central Intelligence Agency analysts agree that they have no clear evidence
that U. S. missions or interests overseas are threatened by foreign state or
terrorist attacks using biological or chemical agents at this time.
According to these officials, terrorist attacks involving the use of
conventional bombs are considered the greatest threat to U. S. overseas
missions. The State Department has suspended expanding its anthrax vaccine
immunization program beyond the pilot site because of the unavailability of
vaccine and it plans to reassess the need for the program after obtaining a
more complete threat assessment.

The State Department's prepositioning of anthrax vaccine at diplomatic posts
in 1998 and the voluntary anthrax vaccine immunization program conducted at
the pilot site to date have been poorly implemented. When a SCUD attack did
not occur, 80 percent of an initial shipment of 8,000 doses of anthrax
vaccine the State Department prepositioned at eight U. S. missions overseas
expired and had to be destroyed. State Department attempts to minimize such
waste by redistributing the unused vaccine to

the Department of Defense to be used elsewhere failed because it could not
provide assurances that the vaccine was properly stored and refrigerated.
Moreover, because the State Department could not provide assurances that the
vaccine was properly stored, the quality of the remaining 20 percent (2, 000
doses) that was used was uncertain. In addition, vaccine requirements for
the voluntary program were not accurately estimated based on a comprehensive
analysis of potential users at all posts beyond the pilot site. As of July
2000, none of the recipients at the pilot site received the full series of
immunizations on schedule because procedures were not implemented that would
allow all recipients to complete the full regimen of anthrax vaccinations on
schedule. Finally, surveillance procedures used in the pilot program to
monitor reactions to the vaccine may be underreporting the incidence of
adverse reactions to the vaccine because recipients were not actively
monitored to determine if they had adverse reactions.

This report contains recommendations for the State Department to take
several measures to better define the need for a voluntary anthrax
immunization program and to improve the implementation of future
immunization efforts if the Department resumes the expansion of its anthrax
vaccine immunization program to other U. S. missions overseas. The State
Department provided written comments on a draft of this report and concurred
with all the report recommendations, stating that they can help improve the
voluntary program when sufficient vaccine becomes available to implement it.
However, the State Department expressed concern about statements made in the
report that it believed reflected a misunderstanding of the prepositioning
effort and the voluntary immunization program, which could mislead readers.
We revised the report to more clearly differentiate the prepositioning of
anthrax vaccine at U. S. missions overseas from the voluntary program.

Background State's Office of Medical Services administers and manages the
State Department voluntary anthrax vaccine immunizations program. The

program's implementation plan calls for the anthrax vaccine to be phased in
on a voluntary basis to all direct hire U. S. government employees, 2 their
family members between the ages of 18 and 65, and Foreign Service National
employees 3 worldwide. State Department employees typically serve a 2- year
tour of duty at U. S. missions overseas before transferring to new
assignments. In addition, State planned to explore the possibility of
providing the vaccine on a voluntary basis to individuals and family members
under the age of 18 or over 65 years of age and pregnant women. The anthrax
vaccine is to be administered following the Food and Drug Administration's
(FDA) guidelines requiring a six- shot series given over 18 months followed
by an annual booster. 4

State purchases the anthrax vaccine from the Department of Defense (DOD),
which currently procures the vaccine for DOD and State anthrax vaccine
immunization programs solely from one private manufacturer, BioPort
Corporation. 5 In 1998, BioPort shut down its production facility for
renovation and to address numerous manufacturing problems identified by FDA
during its inspections. As of this date, the manufacturer has not
satisfactorily responded to FDA's concerns. Consequently, the facility has
not received approval from FDA to release additional lots of vaccine. On
July 11, 2000, DOD announced that it was temporarily scaling back its
anthrax vaccine immunization program because of the inadequate supply of
FDA- approved anthrax vaccine. As a result, the State Department will

2 Direct hire U. S government employees includes all Civil Service, Foreign
Service, and U. S military personnel from all U. S. government agencies,
bureaus, and departments. U. S. military personnel, however, receive anthrax
vaccine immunizations under the mandatory DOD anthrax vaccine immunization
program.

3 Foreign Service National employees are primarily host country citizens
hired by U. S. government agencies at U. S. missions overseas. 4 The regimen
for this vaccine is an initial series of three vaccinations at 2- week
intervals, followed by three additional vaccinations at 6, 12, and 18 months
with annual boosters thereafter.

5 We have testified on various issues surrounding DOD's anthrax vaccine
immunization program. Medical Readiness: Safety and Efficacy of the Anthrax
Vaccine (GAO/ T- NSIAD- 99- 148, Apr. 29, 1999); Medical Readiness: Issues
Concerning the Anthrax Vaccine( GAO/ T- NSIAD- 99- 226, July 21, 1999);
Anthrax Vaccine: Safety and Efficacy Issues (GAO/ T- NSIAD- 00- 48, Oct. 12,
1999); and Medical Readiness: Safety and Efficacy of the Anthrax Vaccine(
GAO/ T- NSIAD- 99- 148, Apr. 29, 1999).

not receive any new supplies of the vaccine for its needs until the
manufacturer receives FDA approval to release additional lots of the
vaccine.

Anthrax Immunization In the spring of 1998, the State Department deployed
anthrax vaccine and

Policy Based on antibiotics as a precautionary measure to a number of U. S.
missions within

Iraqi SCUD ballistic missile range against possible biological weapon
Uncertain Threats

attack. These supplies were stockpiled with the intent to administer post-
exposure immunization and antibiotic treatment following an anthrax attack.
6 According to the Director of Environmental and Preventative Medicine at
State's Office of Medical Services, the stockpiling of anthrax vaccine at U.
S. missions within Iraqi SCUD range was based on an intelligence assessment
that Iraq had SCUD missiles capable of carrying anthrax and would use them
in an attack against U. S. missions. The Director could not, however,
identify the specific threat assessment or the agency that did the
assessment. 7

Following the August 1998 bombings of the Nairobi and Dar Es Salaam
embassies, security concerns were heightened, and, according to the State
Department's Medical Director, the view that posts outside of SCUD range
were also at high risk led to the development of more extensive measures to
protect U. S. missions overseas from chemical and biological attack. In
January 1999, the Under Secretary of State for Political Affairs requested
the National Intelligence Council 8 to conduct an assessment of chemical and
biological threats to U. S. interests overseas 9 and to complete the
assessment in 48 hours. In a February 1999 Decision Memorandum to the Under
Secretary of State for Management, the Office of Medical Services
recommended that a worldwide anthrax immunization policy be adopted

6 The administration of antibiotics and anthrax vaccine, if administered
within 48 hours of exposure can be life saving. 7 Intelligence agencies
continuously assess the foreign and domestic threats to the United States
from foreign states and terrorists. The U. S. foreign intelligence
community, which includes the Central Intelligence Agency, the Defense
Intelligence Agency, and others, monitors the foreign- origin threats to the
United States.

8 The National Intelligence Council is an organization composed of 12
National Intelligence Officers who report directly to the Director of
Central Intelligence. 9 U. S. interests overseas are defined as including
embassies, military and civilian facilities, international transportation,
and businesses.

on a voluntary basis. It based its recommendation primarily on conclusions
presented in the National Intelligence Council assessment that (1) U. S.
missions overseas were at increased risk of a chemical and biological attack
and (2) terrorist groups can procure and utilize biological weapons. The
State Department formally adopted a voluntary, worldwide anthrax
immunization policy in May 1999.

However, according to several intelligence analysts involved in conducting
the assessment, because they were only given 48 hours to complete the
assessment, it should be considered extremely limited in how it is used as a
basis for State's anthrax vaccination program. The assessment was more
general in nature and was not a comprehensive vulnerability study of U. S
interests abroad. The assessment did not evaluate the relative risks of
chemical and biological attacks on each potential target overseas. It did
not identify specific biological or chemical agents that foreign states or
terrorist groups would employ, whether states or terrorist groups actually
have them in their possession, or have the capability to use and weaponize
any agents to effectively disseminate them and cause casualties. While the
threat assessment predicted the chance of a chemical and biological attack
against U. S. interests in the next decade, the intelligence analysts said
this was based on their best judgment from a reading of all the available
reporting rather than on a sound methodology. The intelligence analysts
also, however, stated that with regard to terrorist groups, intelligence
community assessments conclude that conventional weapons continue to be of
highest concern. 10

10 In our past reporting, we have noted that the Central Intelligence Agency
has found that interest among non- state actors, including terrorists, in
biological and chemical materials is real and growing, but that terrorists
are less likely to use chemical and biological weapons than conventional
explosives. See Combating Terrorism: Need for Comprehensive Threat and Risk
Assessments of Chemical and Biological Attacks( GAO/ NSIAD- 99- 163,

Sept. 7, 2000).

Similarly, the Coordinator of Chemical and Biological Countermeasures at
State's Bureau of Diplomatic Security told us that the intelligence
community has no clear evidence supporting the notion that states such as
Iraq would use biological weapons such as anthrax against U. S. missions
overseas or that U. S. posts outside of SCUD range are also at risk of
biological and chemical attack. In addition, these officials agree that
intelligence community assessments offer no clear evidence that terrorist
groups currently have the capability to develop and deploy anthrax. 11
According to these officials, the more likely threat from terrorist groups
is the use of conventional bombs against U. S. missions.

Problems in The State Department's efforts to stockpile anthrax vaccine at
diplomatic

Administering Anthrax missions for post- exposure treatment against a
possible anthrax attack by

Iraq and establish a voluntary anthrax immunization program for its Vaccine
at U. S.

employees and their dependents at U. S. missions overseas have been Missions
Overseas

poorly implemented. In prepositioning the vaccine at eight U. S. missions
overseas and at the State Department's Office of Medical Services in 1998
and implementing a pilot program at one location starting in October 1999,
the Office of Medical Services did not (1) document whether the vaccines
stockpiled at U. S. missions overseas were kept at proper temperatures to
ensure that unused vaccine could be redistributed to DOD for potential use
elsewhere, (2) accurately estimate future vaccine requirements for U. S.
missions overseas based on a comprehensive analysis, (3) develop procedures
allowing for recipients assigned to high- threat missions to receive
complete and timely anthrax vaccine immunizations, and (4) actively monitor
adverse reactions to the vaccine.

11 Our past testimony also points out that public statements regarding
intelligence community assessments of the chemical and biological threat to
U. S. interests do not contain important caveats or qualifications that must
be recognized regarding limitations to terrorist capabilities to weaponize
and disseminate chemical and biological weapons. See Combating Terrorism:
Linking Threats to Strategies and Resources( GAO/ T- NSIAD- 00- 218,

July 26, 2000).

Anthrax Vaccine Stockpiled The State Department could not redistribute
unused anthrax vaccine

at Overseas Posts and the stockpiled at overseas posts in 1998, and 80
percent of the vaccine had to

State Department Was Not be destroyed upon its expiration date. State made
its request for the initial

Used and Needed to Be supply of anthrax vaccine from DOD in April 1998 and
requested that DOD

provide 12,000 doses of the vaccine and other chemical defense materials
Destroyed

for the protection of personnel assigned to U. S. missions in the Persian
Gulf region. Because of anthrax vaccine supply shortages within the
military, DOD was only able to initially provide 8, 000 doses, with the
remaining 4, 000 doses to be provided at a later date. 12 In May 1998, 780
vials (equivalent to 7, 800 doses, with each vial containing 10 doses) of
the anthrax vaccine were received by State and shipped to eight U. S.
missions in the Persian Gulf region to be prepositioned as a contingency
measure against Iraqi SCUD attacks. An additional 20 vials, or 200 doses,
were provided to the State Department's Office of Medical Services. The
shipment of 800 vials consisted of two lots, with one lot of 61 vials having
an expiration date of February 6, 1999, and the other lot of 739 vials
expiring on February 23, 1999.

According to the State Department, when Iraqi SCUD attacks did not occur as
anticipated and therefore the stockpiled anthrax vaccine was not needed, it
tried to redistribute the unused vaccine to DOD before its expiration.
However, DOD refused to accept the vaccine when State could not provide
assurances of the vaccine's “cold chain of custody”- that is,
whether it was properly refrigerated at required temperatures at State
medical clinics. Anthrax vaccine has a 1- year shelf life and the vaccine
must be stored at 35.6 to 46.4 degrees Fahrenheit 13 and constantly
monitored for proper temperature, expiration dates and replacement. None of
the U. S. missions where the anthrax vaccine was prepositioned had
refrigeration units with automatic temperature monitoring alarms that could
ensure the cold chain of custody for the anthrax vaccine was maintained. DOD
requires that all refrigeration systems have temperature- indicating devices
to maintain and monitor proper storage temperatures for anthrax vaccine. If
temperatures are manually monitored, DOD requires that readings must be
annotated every 12 hours and a record

12 The State Department paid DOD $144, 620 for 12, 000 doses of anthrax
vaccine, antidote treatment kits, and injection units. 13 Storage
requirements call for the vaccine to be stored at 2 to 8 degrees Celsius
(35.6 to 46. 4 degrees Fahrenheit) and the vaccine cannot be frozen or used
after the expiration date on the package.

of these readings must be maintained at the location of the refrigeration
system.

The Project Manager for the State Department anthrax vaccination program
stated that existing refrigeration units at U. S. missions were used to
maintain vaccines at proper temperatures. According to State, the vaccine
was properly stored with other refrigerated vaccines at required
temperatures in accordance with State Department and FDA guidelines on
storage and administration of vaccines. The refrigerators also had
thermometers that were checked by the nurses, but the health units kept no
written records of their temperature monitoring of the anthrax vaccine
because they were not required to do so. However, DOD officials told us that
with no assurances of the viability of the vaccine, they could not accept
the vaccine for use elsewhere. Consequently, 642 of the 800 vials- or over
80 percent of the vaccine- had to be destroyed on their expiration date,
including the 20 vials distributed to State's Medical Services Office in
Washington, D. C. According to Office of Medical Services data, eight vials
were used at two U. S. missions.

State stated that FDA guidelines on the storage and administration of
anthrax vaccine only require it to store the product at the required
temperatures, but do not require it to maintain records of refrigerator
temperatures. Recording refrigerated temperatures of vaccine is only
required for DOD users of the vaccine. In addition, State stated that even
if temperature records were kept, DOD would not be able to use the
additional vaccine because DOD was trying to manage the use of its own
vaccine to minimize waste in its own program. The Director of the Anthrax
Vaccine Immunization Program at the U. S. Army Surgeon General, however,
told us that the main reason for not accepting State's unused vaccine was
the lack of proof of the vaccine's cold chain and DOD would have accepted
the vaccine and used it quickly if the vaccine's cold chain was verified.

Exchanges of Vaccine Despite DOD's refusal to accept the vaccine because of
the lack of

Stored at Pilot Site Could Be assurances that it met the cold chain of
custody, State Department medical

of Questionable Quality personnel at the U. S. mission where the pilot
program was conducted made

a series of anthrax vaccine exchanges with a nearby U. S. military
installation. However, without assurances that the vaccine was properly
stored at the pilot site, it is possible the vaccine rotated may have been
substandard. In January 1999, State medical personnel at the mission
arranged to rotate the total number of vials of anthrax vaccine at the

mission (150 vials) with the military installation before the vaccine
expired in February 1999. The Head Nurse at the pilot site's medical unit
said that these vials were used to immunize U. S. military service members
at the installation. Officials at the installation, in exchange, provided
the mission with 150 vials of anthrax vaccine with an expiration date of
February 23, 2000. The U. S. mission used 30 of these vials to administer
immunizations to State Department employees and their dependents during the
pilot program but the remaining 120 vials were returned to the military
installation in exchange for 30 additional vials of vaccine with a later
expiration date of September 2001. These vials are being used to continue
pilot program immunizations as well as for contingencies at the mission.

According to a State Department Medical Services' official, medical
personnel at the pilot mission were able to meet the cold chain of custody
criteria by manually monitoring the vaccine's refrigerated temperatures
rather than storing the vaccine in refrigerators with automatic temperature
monitoring alarms. However, the official said that medical personnel at the
mission did not maintain any records of their manual monitoring because they
were not required to do so. A DOD official from the Office of
Counterproliferation Policy involved in reviewing State Department anthrax
vaccine requirements told us that, because DOD did not receive assurances
that the vaccine was stored and refrigerated at the proper temperatures, the
vaccine rotated to the military unit might have been of questionable
quality. We did not determine whether soldiers receiving the vaccine from
the vials had any ill effects from the vaccine.

State's Medical Services office had plans to purchase new refrigeration
units for delivery to 40 high- threat U. S. posts, including the pilot post
at a cost of $160,000 to enable their medical units to maintain the cold
chain of custody for future supplies of the vaccine. Medical Service
officials say, however, that their purchase is being reconsidered because
vaccine shortages have delayed the need for the refrigeration units, and
they want to explore less expensive alternatives.

Future Vaccine Program State's request for additional anthrax vaccine for
expansion of the program

Requirements Were was based on inadequate data and analysis. In December
1999, State's

Overestimated Office of Medical Services submitted a request to DOD for 8,
360 doses of

additional anthrax vaccine for expansion of the anthrax vaccination program
to State Department personnel in countries designated as high- threat areas
during fiscal year 2000. The request was based on an estimate that 50
percent of U. S. government direct hires and their

dependents age 18 and over and 30 percent of the Foreign Service Nationals
at each of the missions would participate in the program. Office of Medical
Services officials acknowledged, however, that these assumptions were not
based on a comprehensive survey of employees at the posts beyond the pilot
site, but on their best guesses.

As shown in table 1, based on these assumptions, 50 percent (54 of 109) of
direct hires and their eligible dependents and 30 percent (78 out of 261) of
Foreign Service Nationals at the pilot post were expected to volunteer for
the anthrax vaccine immunizations. Altogether, 36 percent of all eligible
personnel at the post were expected to participate. As shown in table 1,
however, from the inception of the pilot project in October 1999 through
July 5, 2000, a total of 15 percent of all U. S. personnel, dependents and
Foreign Service National employees at the post actually volunteered for
immunizations. 14 While 45 percent of all eligible U. S. direct hires and
their dependents at the mission volunteered for the immunizations, only 3
percent of all Foreign Service Nationals employed at the mission accepted
the shots. Actual participation of U. S. direct hires and their dependents
at the pilot site (45 percent) was therefore close to the State Department
projection of 50 percent, while actual participation of foreign service
national employees (3 percent) was significantly less than the projected 30
percent.

14 Seven U. S. military personnel assigned to the U. S. mission also
received anthrax vaccine immunizations. However, they are excluded fromthe
number of U. S. personnel who actually volunteered for immunizations because
they are required to get immunizations under the mandatory DOD program.

Table 1: Expected and Actual Participation Rates in the Pilot Program State
Department

projected Actual Personnel

Total number of participation rate

participation rate b category eligible personnel a

(percent) (percent)

U. S. direct hire 109 55 (50) 49 (45) employees and dependents

Foreign Service 261 78 (30) 7 (3) National Employees Total 370 133 (36) 56
(15)

a On board as of November 18, 1999. b As of July 5, 2000, and excluding U.
S. military personnel

Source: Department of State Office of Medical Services.

Procedures Were Not None of the U. S. direct hires, their dependents, and
Foreign Service

Implemented to Provide National employees who volunteered for anthrax
vaccinations at the pilot

Complete and Timely site received the full six- dose regimen of the vaccine
as of July 2000, and

Immunization of All several recipients could not complete the shot regimen
after their transfer

from the mission. One difficulty the State Department faced in Recipients at
High- Threat

implementing a voluntary worldwide anthrax program was administering
Missions

the required series of six vaccinations, which takes 18 months to complete
to a workforce that typically transfers after serving a 24- month tour of
duty at an overseas mission. The State Medical Services Office adopted a
phased anthrax vaccination program, beginning with personnel assigned to
high- threat U. S. missions and phasing in other missions worldwide,
believing it was the best way to immunize a mobile State Department
population and to supply U. S. missions with limited supplies of the
vaccine. However, State's Medical Office did not establish procedures to
start offering anthrax vaccine immunizations to employees and their
dependents before their arrival at pilot site. As a result, several
recipients at the pilot site could not complete the full regimen of anthrax
vaccine immunizations on schedule after they transferred from the mission to
other locations because of the short supply of anthrax vaccine.

As of July 5, 2000, none of the recipients at the pilot site received the
full six- shot series. The first series of anthrax vaccine immunizations in
the pilot program started in October 1999. Of the 56 U. S. direct hires,
dependents, and Foreign Service Nationals who participated in the

program, 3 voluntarily dropped out and the remaining 53 participants have
received varying doses of the vaccine. As shown in table 2, 31 of the 53
recipients of the anthrax vaccine have received the first three doses in the
six- shot series and 22 have received four to five doses.

Table 2: Number of Anthrax Vaccinations Received by Recipients in the Pilot
Program (as of July 5, 2000)

Employee category First 3 doses 4- 5 doses

U. S. direct hires 15 14 Dependents and other 9 8 Foreign service nationals
7 0

Total 31 a 22

a Three additional U. S. direct hire recipients voluntarily discontinued
from the program after receiving the first two shots. Source: Office of
Medical Services, Department of State.

Because State did not implement procedures to ensure that participants at
the pilot site complete the immunization regimen on schedule, 20
participants who have transferred from the mission will not be able to
complete the full regimen of shots. A State medical official said that,
because of the short supply of vaccine, anthrax inoculations would be
discontinued for personnel moving to nonthreat posts, but continue for those
moving to other high- threat posts. State personnel transferring to
nonthreat U. S. posts would have to stop the shot regimen and restart the
regimen again when they transfer back to high- threat posts. According to
FDA, however, no studies have been conducted to determine the impact on the
vaccine's effectiveness and immunity from anthrax if six- shot regimen is
interrupted.

In the past, FDA officials have emphasized the need for the DOD anthrax
vaccine immunization program to strictly follow the FDA- approved regimen of
six doses administered over 18 months and an annual booster shot afterward,
without deviations. In a September 29, 1999, memorandum to DOD, the Director
of FDA's Center for Biologics Evaluation and Research states that
“this schedule is the only regimen shown to be effective in protecting
humans against anthrax and is the only schedule approved by FDA.” The
Director also states that “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.” In a testimony before the Senate Armed Services Committee
on July 12, 2000, the same FDA Director again cautioned that an interruption
in the vaccine schedule would not be consistent with FDA- approved label
directions for administering the six- shot series. However, the Director
added that because of the shortage of FDA- approved vaccine and the views of
an advisory committee on immunization practices regarding interruptions in
the administration of vaccines, 15 FDA “would not object” to a
resumption of shots after an interruption.

Reporting Procedures May State adopted a surveillance system that may have
led to underreporting of

Be Understating Adverse adverse reactions to anthrax vaccine. Adverse events
include injection- site

Reactions to the Anthrax reactions (such as redness and swelling) and
systemic events (such as

Vaccine hypersensitivity, fever, and muscle aches). State adopted DOD
procedures

in which adverse events after vaccination are to be submitted to the Vaccine
Adverse Event Reporting System (VAERS) using the VAERS form. VAERS is a
passive surveillance system used to alert FDA and the Center for Disease
Control and Prevention of adverse events that may be associated with
licensed vaccines. VAERS is considered a passive surveillance system since
information is voluntarily reported to VAERS by health care providers,
patients, or families, who are encouraged to report any adverse events after
a person receives the vaccine. Individual vaccinations are documented in the
individual health record and State's Medical Immunization Tracking System.

According to State Office of Medical Services' data, out of the 53 anthrax
vaccine recipients in the pilot program, nine reported adverse reactions and
eight of them were female- about 30 percent of all female recipients. They
reported symptoms such as “hard nodules,” “lumps,”
or “knots” on the site of injection, prolonged soreness of the
arm, and for three recipients, the knot or nodule was described as lasting 4
to 6 weeks. State records also show that three additional female recipients
also had reactions, but chose not to report them as adverse reactions
through the VAERs reporting

15 In a September 1998 memorandum on DOD policy on deviation from anthrax
vaccine immunization schedule, the Assistant Secretary of Defense for Health
Affairs cited the Advisory Committee on Immunization Practices, U. S. Public
Health Service, as stating in 1994 that it did not generally recommend
reinstitution of the entire series of a vaccine because of an interruption
in the schedule. For the anthrax vaccine, this approach was supported by
unpublished data in humans showing a robust antibody response to the anthrax
vaccine 1 to 2 years after a partially completed primary series. However,
DOD policy continues to adhere to the published immunization schedule.

system. The nurse at the pilot mission's medical clinic said that there have
been a wide range of reactions to the vaccine among the participants, but
only adverse reactions known to be associated with anthrax vaccine, as
indicated in FDA instructions accompanying the vaccine, were documented. She
said that because the burden is on the recipients to report adverse
reactions in a passive reporting system, she did not encounter any unusually
delayed reactions, but believed she could have obtained more information on
reactions using procedures to actively monitor recipients.

In our previous testimony on the DOD anthrax immunization program, we
reported on the relative merits and weaknesses of the VAERS passive
surveillance system in determining adverse reactions. 16 VAERS has several
advantages. It is a relatively affordable way to supplement data on short-
term adverse events that are collected using active means during clinical
trials before a vaccine is licensed. Most important, however, VAERS serves
as a signal for the detection of previously unreported adverse events and/
or unexpected increases in reported events. Both the general public and
doctors can report adverse events to the system, and the data is open to
public scrutiny.

However, we reported that VAERS also has several disadvantages. Studies show
that adverse events are often substantially underreported in a passive
surveillance system. One study cited that “only about 1 percent of
serious events” attributable to drug reactions are reported to FDA. 17
Reporting of adverse events appears to depend on several factors, such as
the clinical seriousness of the event, the length of time between the shots
and the event, and health care workers' awareness of and obligation to
report particular adverse events. Also, outcomes with delayed onset after
vaccination or outcomes not generally recognized to be associated with
vaccination are often underreported. According to the National Vaccine
Information Center, there is no mechanism within VAERS for a 1-, 3-, or 10-
year follow- up to evaluate vaccine reactions that have a long latency
period. According to the Centers for Disease Control, the limitations of

16 Medical Readiness: Issues Concerning the Anthrax Vaccine( GAO/ T- NSIAD-
99- 226, July 21, 1999). 17 D. A. Kessler, “Introducing MED Watch: A
New Approach to Reporting Medication and Devise Adverse Effects and Product
Problems,” Journal of the American Medical Association, vol. 269
(1993), pp. 2765- 2768, and H. D. Scott, et al., “Rhode Island
Physicians'

Recognition and Reporting of Adverse Drug Reactions,” Rhode Island
Medical Journal, vol. 70 (1987), pp. 311- 316.

VAERS data suggest it is not a valid source for assessing the rate of
adverse events. In an active surveillance system, which is generally more
costly to administer, health care workers monitor people that have been
vaccinated to find out if they have had adverse reactions.

Conclusions The State Department established the worldwide voluntary anthrax
immunization program based on a general assessment of chemical and

biological threats to U. S. interests overseas. This assessment did not
evaluate the relative risk of chemical and biological attacks on each
potential target, identify the chemical and biological agents likely to be
used, or assess the ability of states or terrorist groups to disperse the
agents and cause mass casualties. As a result, the extent to which U. S.
overseas missions are vulnerable to chemical and biological attacks is
uncertain. Therefore, the basis for State's worldwide anthrax vaccine
immunization program is questionable.

Notwithstanding the issues surrounding the need for a worldwide immunization
program, State Department efforts to immunize its employees and their
dependents were poorly implemented. Most of the vaccine prepositioned at U.
S. missions overseas and at the State Department in 1998 were not used or
redistributed for use elsewhere and the vaccine had to be destroyed upon its
expiration date. The State Department also did not have a sound basis to
estimate the level of future vaccine requirements for participants in the
voluntary immunization program. In addition, none of the anthrax vaccine
recipients in the pilot program received the full series of anthrax
vaccinations because State did not implement procedures that would have
enabled participants to begin the required regimen of immunizations before
their arrival at high- threat missions and to complete the regimen on
schedule. According to FDA, failure to complete the full six- shot regimen
on schedule will leave these recipients without full protection from
anthrax. Finally, adverse reactions to the anthrax vaccine from the pilot
program could have been underreported because passive, rather than active
procedures, were used to monitor reactions. In previous testimony on the use
of passive surveillance procedures to track adverse reactions in DOD's
anthrax vaccine immunization program, we reported several weaknesses in
using passive surveillance systems and studies showing that adverse events
are underreported.

Because the anthrax vaccine is in short supply, the State Department has
suspended expansion of its vaccination program to other U. S. missions

overseas. If the vaccine becomes available in the future and the State
Department resumes the vaccination program, these issues must be addressed
to minimize the potential waste of the vaccine and maximize the potential
for full immunization of participating employees.

Recommendations for To better define and evaluate the need for the voluntary
anthrax

Executive Action immunization program and improve the implementation of any
future

immunization efforts, we recommend that the Secretary of State take the
following steps before resuming the vaccine program in U. S. missions
overseas:

To determine whether a voluntary anthrax vaccine immunization program is the
most effective approach to protecting U. S. personnel at U. S. missions
overseas, obtain from the intelligence community a more complete assessment
of the threat and probability of a chemical and biological attack on U. S.
diplomatic and consular missions. This assessment should address the (1)
relative risks of a chemical or biological attack for each mission, (2)
types of chemical and biological agents likely to be used, and (3) ability
of states or terrorist groups to disperse these agents and cause casualties.
In addition, the Secretary should reassess the need to continue the pilot
program until a complete threat assessment is conducted. To improve the
implementation of any future immunization efforts,

(1) require that appropriate vaccine storage and redistribution mechanisms
are in place before anthrax vaccine is shipped overseas; (2) develop
estimates of anthrax vaccine requirements based on actual experience at the
pilot location and a site survey of U. S. employees, their dependents and
foreign service nationals at the next locations to receive the vaccine; (3)
develop procedures that provide for each participating employee assigned to
high- risk posts to complete the full six- shot regimen of anthrax vaccine
on schedule and also seek additional scientific evidence in consultation
with FDA and DOD to determine the impact of deviations from the approved
dosage schedule on immunity; and (4) take steps to determine whether active
surveillance procedures would be more appropriate to track adverse reactions
of future recipients in the program.

Agency Comments The State Department provided written comments on a draft of
this report. They are reprinted in appendix II. The State Department
concurred with all

the report recommendations, stating that they can help improve the voluntary
program when sufficient vaccine becomes available to implement it. However,
State expressed concern about statements made in the report that it believed
were presented out of context. State commented that we confused two
initiatives: (1) the initial 1998 prepositioning of anthrax vaccine at
certain high threat posts within SCUD ballistic missile range of Iraq and
(2) the voluntary anthrax vaccine immunization program. We agree that the
report was not as clear as it could have been in describing the two
initiatives and we have made additional changes in the report to make a
clearer distinction between the efforts. In addition, State provided
technical comments that were included in the report where appropriate.

With respect to our finding that State established its voluntary anthrax
vaccine immunization policy based on a threat assessment that was limited
and general, State acknowledged that it did not know the relative risks of a
biological attack at U. S. missions overseas, but it said that the decision
to stockpile anthrax vaccine in 1998 and begin a program in 1999 was based
on a perceived threat of biological attack. However, State does not
challenge our conclusion that a decision to start and devote resources to an
anthrax immunization program should be based on a complete threat assessment
using valid and objective threat data and fully evaluating the risks of
biological and chemical attacks on U. S. missions overseas. State agreed
with our recommendation to request a more complete threat assessment from
the intelligence community and to re- evaluate the need for a voluntary
immunization program.

Regarding the destruction of anthrax vaccine stockpiled at selected U. S.
missions and the State Department, State commented that the vaccine had to
be destroyed because it expired and not because it was improperly
maintained. State also stated that even if temperature records were kept,
DOD could not utilize State's unused vaccine because DOD did not need
additional vaccine and was trying to manage the use of its own to minimize
waste from its own program. We agree that the vaccine was destroyed because
it expired and revised our report to make that point more explicit. However,
we believe the central point is that DOD would not accept the vaccine for
redistribution to be used elsewhere before expiration because State could
not provide assurances that the vaccine was properly refrigerated at
required temperatures. Consequently, most of the 8, 000 doses of anthrax
vaccine stockpiled at U. S. missions had to be destroyed upon their
expiration. Further, DOD officials told us that they would have accepted the
vaccine and could have quickly used it elsewhere if the vaccine's cold chain
was verified.

With respect to maintaining the cold chain of custody of anthrax vaccine
stockpiled at several U. S. missions overseas, State claimed that the
vaccine was properly refrigerated at required temperatures at U. S. missions
and that it was not required to document temperature monitoring. While we
agree that State was not required to document temperature monitoring, it
would have been prudent to maintain the cold chain standards at all times to
ensure that anthrax vaccine stocks could be redistributed to DOD prior to
their expiration date in order to minimize vaccine wastage. Redistribution
through the DOD supply system requires written validation that the vaccine
was monitored for proper storage temperature. State acknowledged that
recording refrigerator temperatures is a prudent practice and based on our
recommendation it is a requirement it will implement in the future.

In response to our finding that future vaccine requirements were not
accurately estimated based on a specific analysis, State indicated that its
estimates were based on health care providers polling Americans and Foreign
Service National employees at the missions to determine their participation.
State claimed that it estimated acceptance rates of 50 percent for U. S.
government employees and dependents and 30 percent for Foreign Service
National employees from a range of responses received from several posts.
However, State Medical officials directly told us that these estimates were
not based on a comprehensive survey of personnel at missions beyond the
pilot site, but on their best guesses. In addition, as State acknowledges,
it did not revise these estimates at the pilot site to account for changes
in circumstances such as changes in personnel and their acceptance of the
vaccine and Foreign Service National employee concerns. We believe that
State must have a sound basis for estimating vaccine requirements that
reflects actual experience, varying circumstances at posts, and a
comprehensive survey of U. S. employees, their dependents and foreign
service nationals at missions designated to receive the vaccine. Based on
our recommendation, State now plans to adjust the estimates based on what is
actually needed at each mission.

Regarding our statement that none of the recipients in the pilot program has
received the full schedule of anthrax vaccine shots, State commented that
because the pilot program started in October 1999, no one in the program
could be fully vaccinated with the series of six shots that takes 18 months
to complete. Our report recognized the difficulty that the State Department
faces in trying to administer the required six- shot series of anthrax
vaccine, taking 18 months to complete to a workforce that typically
transfers to new locations after a 24- month tour of duty at an

overseas mission. Knowing that, however, State did not implement procedures
to ensure that employees in the pilot program who volunteered for
immunizations would have the opportunity to receive the complete six shots
on schedule without interruption before transferring to other locations. The
most complete and accurate data State provided to us on anthrax vaccine
recipients at the pilot site was as of July 2000 and showed that no one
received the full series of shots, including 20 participants who transferred
from the mission to other locations. In concurring with our recommendation,
State said that when sufficient vaccine becomes available to implement the
program, it would take additional steps to allow recipients who move to
different posts to continue the vaccine series consistent with the FDA-
approved vaccine dosage schedule.

In response to our statement that procedures used in the pilot program to
monitor reaction to the vaccine may be underreporting the incidence of
adverse reactions, State commented that medical staff at the pilot post took
several measures to ensure that potentially adverse events were recorded,
including the “Statement of Information and Affirmation” that is
distributed to each recipient. As our report indicates, State adopted
passive monitoring procedures used under the VAERS passive surveillance
system and that the use of these procedures has been demonstrated to
substantially underreport adverse events. The health care practitioner at
the pilot site health unit told us that the use of active monitoring
procedures would have yielded more information on adverse reactions. State
previously provided us with information on its proposal to work with the
Center for Disease Control and Prevention to develop a patient survey card
to record reactions to anthrax vaccine. This “health report
card” was not used in the pilot program; therefore, we did not include
it when we assessed efforts to monitor adverse reactions. State did not
provide us with details of its proposal or how it will be implemented so
that we could assess it. However, State concurred with our recommendation to
implement an active surveillance system when sufficient vaccine becomes
available to implement the program.

As agreed with your offices, unless you publicly announce the contents
earlier, we plan no further distribution of this report until 30 days after
its issue date. At that time, we will send copies of this report to Senator
Joseph Biden, Jr., Ranking Minority Member, Senate Committee on Foreign
Relations; Senator Fred Thompson, Chairman, and Senator Joseph Lieberman,
Ranking Minority Member, Senate Committee on Governmental Affairs; Senator
Ted Stevens, Chairman, and Senator Robert Byrd, Ranking

Minority Member, Senate Committee on Appropriations; Representative Sam
Gejdenson, Ranking Minority Member, House Committee on International
Relations; Representative Dan Burton, Chairman, and Representative Henry
Waxman, Ranking Minority Member, House Committee on Government Reform; and
Representative Bill Young, Chairman, and Representative David Obey, Ranking
Minority Member, House Committee on Appropriations . We will also send
copies to the Honorable Madeline Albright, Secretary of State and the
Honorable William S. Cohen, Secretary of Defense. Copies will also be made
available to others on request.

If you have any questions regarding this report, please contact me or Sushil
K. Sharma at (202) 512- 3992. Jason Fong, Robert Repasky, and Susan Woodward
also made key contributions to this report.

Kwai- Cheung Chan Director, Applied Research and Methods

Appendi Appendi xes xI

Scope and Methodology To determine the basis for the Department of State
policy to immunize its employees with anthrax vaccine, we interviewed
officials and obtained documents from the Office of Medical Services and the
Office of Chemical Biological Countermeasures Program, Bureau of Diplomatic
Security at the Department of State. We also interviewed intelligence
analysts at the Central Intelligence Agency and reviewed a classified
National Intelligence Council assessment on chemical and biological threats
to U. S. interests overseas and a classified intelligence community
assessment on the foreign biological and chemical weapons threat to the
United States. In addition, we reviewed the First Annual Report of the
Advisory Panel to Assess Domestic Response Capabilities for Terrorism
Involving Weapons of Mass Destruction.

To examine how well the State Department's voluntary anthrax vaccine
immunization program was implemented, we interviewed officials and obtained
documents from the Office of Medical Services at the Department of State;
State Department medical personnel at a U. S. mission in the Persian Gulf
region where anthrax vaccinations were carried out; the U. S. Army Surgeon
General; the Office of Counterproliferation Policy, Requirements, and Plans
under the Assistant Secretary of Defense for Strategy and Threat Reduction
at the Department of Defense; and the Food and Drug Administration. We also
analyzed assumptions used by the State Department Office of Medical Services
to estimate anthrax vaccine requirements for U. S. missions overseas; data
on anthrax vaccine supplied to overseas posts; and medical and demographic
information on U. S. government employees, dependents and foreign service
national employees who received anthrax vaccine immunizations at a U. S.
mission in the Persian Gulf region from October 1999 to July 2000.

We conducted our review from December 1999 through November 2000 in
accordance with generally accepted government auditing standards.

Appendi xII Comments From the Department of State

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Appendix I

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Appendix II

Appendix II Comments From the Department of State

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