GAO

United States General Accounting Office

Report to Congressional Requesters

December 2000 STATE DEPARTMENT

Serious Problems in

the Anthrax Vaccine

Immunization

Program

GAO-01-21

Page 1 GAO-01-21 State Department

United States General Accounting Office

Washington, D.C. 20548 Letr

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.
Page 2 GAO-01-21 State Department

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
Page 3 GAO-01-21 State Department

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.
Page 4 GAO-01-21 State Department

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 employees3 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).
Page 5 GAO-01-21 State Department

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

Policy Based on

Uncertain Threats

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

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

Iraqi SCUD ballistic missile range against possible biological weapon

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 Council8 to conduct an assessment of chemical

and biological threats to U.S. interests overseas9 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.
Page 6 GAO-01-21 State Department

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).
Page 7 GAO-01-21 State Department

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

Administering Anthrax

Vaccine at U.S.

Missions Overseas

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

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

Iraq and establish a voluntary anthrax immunization program for its

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

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).
Page 8 GAO-01-21 State Department

Anthrax Vaccine Stockpiled

at Overseas Posts and the

State Department Was Not

Used and Needed to Be

Destroyed

The State Department could not redistribute unused anthrax vaccine

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

be destroyed upon its expiration date. State made its request for the initial

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

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 Fahrenheit13 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.
Page 9 GAO-01-21 State Department

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

Stored at Pilot Site Could Be

of Questionable Quality

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

assurances that it met the cold chain of custody, State Department medical

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
Page 10 GAO-01-21 State Department

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

Requirements Were

Overestimated

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

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

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
Page 11 GAO-01-21 State Department

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 from the number of U.S. personnel who actually

volunteered for immunizations because they are required to get immunizations under the

mandatory DOD program.
Page 12 GAO-01-21 State Department

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

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

Implemented to Provide

Complete and Timely

Immunization of All

Recipients at High-Threat

Missions

None of the U.S. direct hires, their dependents, and Foreign Service

National employees who volunteered for anthrax vaccinations at the pilot

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

several recipients could not complete the shot regimen after their transfer

from the mission. One difficulty the State Department faced in

implementing a voluntary worldwide anthrax program was administering

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

Personnel

category

Total number of

eligible personnela

State Department

projected

participation rate

(percent)

Actual

participation rateb

(percent)

U.S. direct hire

employees and

dependents

109 55 (50) 49 (45)

Foreign Service

National Employees

261 78 (30) 7 (3)

Total 370 133 (36) 56 (15)
Page 13 GAO-01-21 State Department

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)

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

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 31a 22
Page 14 GAO-01-21 State Department

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

Be Understating Adverse

Reactions to the Anthrax

Vaccine

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

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

reactions (such as redness and swelling) and systemic events (such as

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.
Page 15 GAO-01-21 State Department

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.
Page 16 GAO-01-21 State Department

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
Page 17 GAO-01-21 State Department

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

Executive Action

To better define and evaluate the need for the voluntary anthrax

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
Page 18 GAO-01-21 State Department

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.
Page 19 GAO-01-21 State Department

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
Page 20 GAO-01-21 State Department

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
Page 21 GAO-01-21 State Department

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
Page 22 GAO-01-21 State Department

Appendix I

Scope and Methodology ApApenednxidexiIs

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.
Page 23 GAO-01-21 State Department

Appendix II

Comments From the Department of State ApendxiI
Appendix II

Comments From the Department of State

Page 24 GAO-01-21 State Department
Appendix II

Comments From the Department of State

Page 25 GAO-01-21 State Department
Appendix II

Comments From the Department of State

Page 26 GAO-01-21 State Department
Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

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Appendix II

Comments From the Department of State

Page 34 GAO-01-21 State Department
Appendix II

Comments From the Department of State

(713058) Letr Page 35 GAO-01-21 State Department
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