United States Government Accountability Office

GAO Testimony before the Subcommittee on 

National Security, Emerging Threats and 

International Relations, Committee on 

Government Reform, House of 

Representatives

ANTHRAX

Federal Agencies Have 

Taken Some Steps to 

Validate Sampling Methods 

and to Develop a NextGeneration Anthrax Vaccine

Statement of Keith Rhodes, Chief Technologist, Center for 

Technology and Engineering, Applied Research and Methods 

For Release on Delivery

Expected at 2:00 p.m. EDT

Tuesday, May 9, 2006 

 

GAO-06-756T 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

May 9, 2006

ANTHRAX

Federal Agencies have taken Some Steps 

to Validate Sampling Methods and to 

Develop a Next Generation Anthrax 

Vaccine 

Highlights of GAO-06-756T, a testimony 

before the Chairman, Subcommittee on 

National Security, Emerging Threats, and 

International Relations, House Committee 

on Government Reform, House of

Representatives 

GAO has done many studies over

the past 7 years on anthrax vaccine 

safety and anthrax detection 

methods. GAO has reported the 

lack of validated methods for 

detecting anthrax contamination 

and has recommended a

coordinated approach to improving 

the overall process for detecting 

anthrax that included a probabilitybased sampling strategy. 

GAO also reported that the vaccine 

has not been adequately tested on

humans; no studies have been done 

to determine the optimum number 

of doses; the long-term safety has 

not been studied and data on shortterm reactions are limited; 

however, women report higher 

rates of reactions than do men.

Given these problems, GAO 

recommended the development, of

a better, alternative vaccine. 

The threat of bioterrorism has long been recognized in the United States and 

abroad. The Department of Defense (DOD) considers inhalation anthrax to 

be the greatest biological warfare threat to U.S. military forces. The U.S. 

Army Medical Research Institute of Infectious Diseases has been conducting 

basic and applied research on biological threats since 1969, in order to 

develop medical countermeasures—prophylactics, vaccines, medical 

diagnostics—to protect warfighters. 

The anthrax incidents in 2001 highlighted major gaps in civilian 

preparedness to detect and respond to anthrax attacks, leading the federal 

government to focus on developing new drugs, vaccines, and therapeutics to 

protect U.S. citizens. As a result, the Department of Health and Human 

Services (HHS) now has major responsibility to ensure that appropriate 

medical countermeasures are available for civilians. And the Department of 

Homeland Security (DHS) assumes major responsibility for coordinating 

federal responses to national incidents of chemical, biological, radiological, 

and nuclear release. 

Despite the many recommendations GAO has made over the past few years 

regarding problems related to the anthrax vaccine’s safety and effectiveness

and the reliability of anthrax detection, deficiencies remain. While agencies 

have taken steps in the right direction, the government still lacks a strategic 

plan outlining how individual agency efforts would lead to the validation of 

the overall sampling process, including methods, and the development of a 

probability-based sampling strategy that accounts for the complexity of 

indoor environments. 

In November 2004, HHS awarded a contract for $877.5 million to procure 75 

million doses of a new anthrax vaccine–the first contract awarded under 

Project Bioshield for medical countermeasures procurement. The terms of 

the award state that the urgency of the current threat requires an accelerated

pace of vaccine development, testing, approval, and procurement. While 

developing vaccine is known to be difficult and highly likely to encounter 

testing and production issues in the best of circumstances, the contract’s 

milestones leave little room for slippage from established delivery dates. 

The biotechnology sector is watching to see if government and industry can 

make this partnership work. Understanding the unique issues in this early 

phase of the biodefense strategy is important. Problems with this initial 

Project Bioshield contract could affect the biotechnology industry’s 

response to future government overtures to develop and procure medical 

countermeasures against the many other biothreat agents still to be 

addressed. 

What GAO Recommends

The Secretary of Homeland

Security needs to develop a formal

strategic plan, including a roadmap, 

outlining how individual agency 

efforts would lead to the validation

of the overall sampling process. 

www.gao.gov/cgi-bin/getrpt?GAO-06-756T.

To view the full product, click on the link 

above. For more information, contact Keith 

Rhodes at (202) 512-6412 or 

rhodesk@gao.gov. 
Mr. Chairman and Members of the Subcommittee: 

We are pleased to be here today to discuss the status of our 

recommendations on two bodies of work that we did at your request: 

licensed anthrax vaccine and anthrax detection methods.1

 As you know, 

the threat of bioterrorism had been recognized for a considerable time in

the United States, as well as internationally. The Department of Defense 

(DOD) has considered inhalation anthrax in an aerosolized form to be the 

greatest biological warfare threat to U.S. military forces for quite some 

time. The U.S. Army Medical Research Institute of Infectious Diseases 

(USAMRIID) has been conducting basic and applied research on biological 

threats since its inception in 1969, in order to develop medical 

countermeasures—for example, prophylactics, vaccines, and medical 

diagnostics—to protect the warfighter. 

The anthrax incidents in September and October 2001 highlighted major 

gaps in our civilian preparedness to detect and respond. It also led the 

federal government to focus attention on the importance of developing

new drugs, vaccines, and therapeutics to protect U.S. citizens. 

Consequently, the Department of Health and Human Services (HHS) has 

the major responsibility to ensure that appropriate medical 

countermeasures are available for the civilian population, while the 

Department of Homeland Security (DHS) has assumed the major 

 1

For our work on anthrax detection methods, see GAO, Anthrax Detection: Agencies Need

to Validate Sampling Activities in Order to Increase Confidence in Negative Results, 

GAO-05-251 (Washington, D.C.: Mar. 31, 2005), and GAO, U.S. Postal Service: Issues 

Associated with Anthrax Testing at the Wallingford Facility, GAO-03-787T (Washington 

D.C.: May 19, 2003). For our work on anthrax vaccine, see Gulf War Illnesses: Questions

about the Presence of Squalene Antibodies in Veterans Can Be Resolved, GAO/NSIAD-99-5 

(Washington, D.C.: Mar. 29, 1999); Medical Readiness: Safety and Efficacy of the Anthrax

Vaccine, GAO/T-NSIAD-99-148 (Washington, D.C.: Apr. 29, 1999); Contract Management: 

Observations on DOD’s Financial Relationship with the Anthrax Vaccine Manufacturer,

GAO/T-NSIAD-99-214 (Washington, D.C.: June 30, 1999); Medical Readiness: Issues

Concerning the Anthrax Vaccine, GAO/T-NSIAD-99-226 (Washington, D.C.: July 21, 1999);

Anthrax Vaccine: Safety and Efficacy Issues, GAO/T-NSIAD-00-48 (Washington, D.C.: Oct.

12, 1999); Medical Readiness: DOD Faces Challenges in Implementing Its Anthrax 

Vaccine Immunization Program, GAO/NSIAD-00-36 (Washington, D.C.: Oct. 22, 1999); 

Medical Readiness: DOD Continues to Face Challenges in Implementing Its Anthrax 

Vaccine Immunization Program, GAO/T-NSIAD-00-157 (Washington, D.C.: Apr. 13, 2000);

State Department: Serious Problems in the Anthrax Vaccine Immunization Program, 

GAO-01-21, (Washington, D.C.: Dec. 13, 2000); Anthrax Vaccine: Changes to the 

Manufacturing Process, GAO-02-181T (Washington, D.C.: Oct. 23, 2001); Anthrax Vaccine: 

GAO’s Survey of Guard and Reserve Pilots and Aircrew, GAO-02-445 (Washington, D.C.: 

Sept. 20, 2002). 

Page 1 GAO-06-756T 
responsibility for coordinating federal responses to national incidents of 

chemical, biological, radiological, and nuclear material release. 

The President’s 2006 federal budget includes $1.8 billion allocated to the 

National Institutes of Health (NIH) to fund biodefense research and 

development activities, which includes the development of new and 

improved medical countermeasures. Additionally, under Project Bioshield, 

a discretionary reserve fund of $5.6 billion has been allocated to procure 

medical countermeasures for the Strategic National Stockpile (SNS) 

through fiscal year 2013.2

To respond to your request, we interviewed officials from federal 

agencies—HHS, including the Food and Drug Administration (FDA); the 

Centers for Disease Control and Prevention (CDC); the National Institute 

of Allergy and Infectious Disease (NIAID); DHS, and DOD. In addition, we

reviewed documents provided by these agencies as well as those provided

by the United States Postal Services (USPS). We visited and interviewed 

the officials of the company that is developing the new anthrax vaccine. 

Finally, we reviewed scientific literature on this issue. We conducted our 

review from March 2006 to April 2006 in accordance with generally 

accepted government auditing standards. 

In today’s testimony, I will specifically report on (1) the problems we 

identified with the anthrax detection methods and the licensed anthrax 

vaccine, (2) recommendations we made, (3) the extent to which federal

agencies have taken corrective actions, and (4) what remains to be done.

With regard to anthrax detection methods, federal agencies responsible 

for responding to the 2001 anthrax incidents adopted a targeted sampling 

strategy that they based on their best judgment at the time. When the level

of contamination is extremely high and dispersed in a facility, the method 

of sampling (for example, using wipes versus swabs) may not be critical, if 

the purpose is to find some contaminant. However, at lower levels, away

of interpreting negative results is needed, and this requirement emphasizes 

the importance of the validation of the methods and the need for 

statistically based sampling strategies. 

Results in Brief 

 2

The SNS is a national repository of medical countermeasures, such as antibiotics and 

vaccines. It is designed to supplement and resupply state and local public health agencies 

in the event of a national emergency anywhere and anytime within the United States or its 

territories. 

Page 2 GAO-06-756T 
Therefore, it is necessary to invest in empirical studies so as to develop a 

probability-based sampling strategy that will account for the complex 

geometry and surface types of many facilities. Using a probability-based 

sampling strategy, together with validated methods for detecting 

contamination, would provide a known level of confidence with which to 

interpret any negative results and would thus enable agencies to be more 

definitive in determining necessary actions. 

The lack of validated methods for assessing contamination in postal 

facilities in 2001 impeded the agencies in responding to the incidents. The 

significance of the lack of validated methods was exemplified in the case 

of one postal facility where negative preliminary results were obtained by 

field-based methods of analysis, with limitations that appear to have been

not well understood by some agencies. 

Given the lack of validated methods for detecting anthrax contamination 

in facilities, we recommended that the Secretary of Homeland Security 

develop a coordinated approach to (1) improve the overall process for 

detecting anthrax and (2) increase confidence in negative test results 

generated by that process. This approach would include working with 

agencies to ensure that appropriate validation studies of the overall 

process of sampling activities, including the methods, are conducted. 

Specifically, we recommended that the Secretary

1. take a lead role in promoting and coordinating the activities of the 

various agencies that have the technical expertise related to

environmental testing; 

2. ensure that a definition of validation is developed and agreed on; 

3. guarantee that the overall process of sampling activities, including 

methods, is validated so that performance characteristics, including 

limitations, are clearly understood and results can be correctly

interpreted; 

4. see that appropriate investments are made in empirical studies to 

develop probability-based sampling strategies that take into account 

the complexities of indoor environments; 

5. ensure that appropriate, prioritized investments are made for all 

biothreat agents; and 

6. ensure that agency policies, procedures, and guidelines reflect the 

results of such efforts. 

Page 3 GAO-06-756T 
When we issued our report, CDC, DHS, and USPS agreed with our 

conclusion—that methods for detecting anthrax contamination in facilities 

were not validated—and with the thrust of our recommendations—calling 

for a coordinated, systematic effort to validate the methods to be used for 

such testing, but they (1) disagreed with or expressed concern about our 

conclusions or the recommendation dealing with targeted versus 

probability sampling, (2) emphasized that validated testing methods for 

anthrax were not available in 2001 and that federal and state organizations 

did the best they could under the circumstances, and (3) identified factors

or issues that need to be considered in validating testing methods. 

In addition, uncertainty over which agency would take the lead role in 

improving the overall process for detecting anthrax, and how studies were 

to be funded, continued after the release of our report. DHS stated that 

while it has overall responsibility for coordinating the federal response 

during future biological attacks, the Environmental Protection Agency

(EPA) had the “primary responsibility for establishing the strategies, 

guidelines, and plans for the recovery from a biological attack” while HHS 

had the lead role for any related public health response and guidelines. 

DHS also stated that it coordinated regularly with EPA’s National 

Homeland Research Center to exchange information on research needs 

and to discuss priorities and gaps for a wide range of security-related 

research areas. DHS stated that it would coordinate with EPA to ensure 

that appropriate investments were made to explore improved sampling. 

Consequently, it was unclear how DHS could ensure that appropriate 

prioritized investments were made for all biothreat agents, with respect to 

agencies other than EPA, and how such priorities and gaps would be 

addressed. 

Although in the past there had been confusion as to which federal agency 

would take the lead, as well as the responsibility for ensuring that our 

recommendations are addressed, DHS is now accepting responsibility. On 

May 3, 2006, DHS told us that DHS recognizes that it is the principal 

agency responsible for coordinating the federal response and would be 

responsible for ensuring that sampling methods, including the process, are 

validated. DHS also would work toward developing a probability-based 

sampling strategy. 

While actions taken by DHS are steps in the right direction, DHS needs to 

develop a formal strategic plan that includes a “roadmap” outlining how 

individual agency efforts would lead to (1) validation of the overall 

process of sampling activities, including the methods, and (2) development 

Page 4 GAO-06-756T 
of a probability-based sampling strategy that takes into account the 

complexity of indoor environments. 

With regard to the licensed anthrax vaccine, we identified a number of 

problems, including, among others, greater understanding of 

1. the need for a six-shot regimen and annual booster shots; 

2. the long-term and short-term safety of the vaccine, including gender 

differences; and 

3. the vaccine’s efficacy. 

In addition, we provided information on the disadvantages of the licensed

anthrax vaccine and the status of federal efforts to develop an improved 

vaccine. Given these problems, and taking into account promising early 

DOD research into an alternative, recombinant protective antigen (rPA) 

vaccine for anthrax, we recommended the development of a secondgeneration vaccine, based on this technology. 

In September 2002 and September 2003, NIAID awarded contracts to 

develop a new rPA vaccine against inhalation anthrax. These contracts to 

develop and test candidate rPA vaccines included the requirement to 

evaluate safety, efficacy, and a potential provider’s manufacturing 

capability to achieve eventual licensing from FDA. 

The objectives in these two NIAID contracts addressed some of the 

problems we identified with the licensed vaccine, including requiring a 

recombinant vaccine to address issues of purity, potency, and 

manufacturing consistency; the need for fewer doses for the civilian 

population; and the capability for postexposure use. However, studies on 

gender differences and long-term safety were not explicitly required. 

In November 2004, in the first contract under Project Bioshield, HHS 

awarded a contract for $877.5 million for the manufacture and delivery of 

75 million doses of rPA anthrax vaccine for SNS. In the production 

contract’s RFP, HHS stated that the urgent nature of the current threat 

required an accelerated pace of development, testing, approval, and 

procurement of the vaccine. While developing vaccine is known to be 

difficult and highly likely to encounter testing and production issues, even 

in the best of circumstances, early development work to ensure safety of

the vaccine and a solid large-scale manufacturing capability had not been 

completed before awarding the full procurement contract. Additionally, 

Page 5 GAO-06-756T 
the contract milestones leave little to no provision for slippage and, being 

a fixed-price contract, if there is an unexpected slip in schedule, the 

financial burden will be fully on the contractor. While the government 

should not pay out money to a contractor unless and until it has met the 

terms of its contract, contractors that do not have the resources to assume 

such risk will not be able to meet the contract requirements, thus limiting 

the pool of companies that are capable of meeting the nation’s needs. 

While the government should be a tough negotiator when contracting for 

major procurements, it is important to understand the unique issues at 

stake in this early phase of implementing the U.S. biodefense strategy. 

Failure of this initial Project Bioshield contract could have an impact on 

how the biotechnology industry responds to government overtures in the 

future for the development and procurement of medical countermeasures 

for the many biothreat agents still to be addressed. 

Background 

The History and Nature of 

Anthrax and the Anthrax 

Vaccine 

Anthrax is an acute infectious disease caused by the spore-forming 

bacterium Bacillus anthracis. It can infect humans but occurs most 

commonly in warm-blooded animals (herbivores) in the agricultural 

regions of the countries that have less standardized and less effective 

public health programs. Human anthrax occurs only rarely in the United 

States from natural causes. However, the anthrax attacks in October 2001 

through contaminated mail resulted in the death of five persons. 

Human infection normally results from an occupational exposure to 

infected animals or animal products. For example, workers may be 

exposed to dead animals or to products such as wool, hides, leather, or 

hair products (especially goat hair). Since there have been no reports, 

even now, of the disease spreading from person to person, anthrax is most 

likely not spread in humans directly.

Anthrax infection can occur in three forms: (1) cutaneous, usually through 

a cut or an abrasion; (2) gastrointestinal, by ingesting contaminated meat; 

and (3) inhalation, by breathing anthrax spores into the lungs. Symptoms 

depend on how the disease is contracted but usually appear within 7 days. 

The disease can be treated with antibiotics: tetracycline and doxycycline 

are preferred, but penicillin, erythromycin, chloramphenicol, or 

ciprofloxacin can also be used. To be effective, treatment should be 

started early. 

Page 6 GAO-06-756T 
The original anthrax vaccine in the United States was developed by 

George Wright and others in the 1950s and was first produced on a large 

scale by the pharmaceutical manufacturer Merck Sharp & Dohme.3

 A 1962 

clinical study that evaluated the safety and effectiveness of the Merck 

vaccine in mill workers formed the basis for the subsequent licensing of a 

modified vaccine in 1970.

4

 The Division of Biologics of the National 

Institutes of Health issued the original license for anthrax vaccine to the 

Michigan Department of Public Health.

5

 In 1995, the facility changed its 

name to Michigan Biologic Products Institute. In 1998, the facility was 

sold, and its name was changed to BioPort Corporation. 

Anthrax Vaccine and the 

Federal Role 

As the lead agency for public health and medical response to manmade or 

natural disasters, HHS has the responsibility for developing, licensing, 

procuring, and storing medical countermeasures, which includes vaccines,

for SNS. In 2002, HHS established the Office for Public Health Emergency 

Preparedness (OPHEP) with responsibility for implementing HHS’s 

strategy for protecting civilians from bioterrorism and other public health 

emergencies. OPHEP coordinates transitions between NIH medical 

countermeasures development, FDA approval and licensing, and CDC 

storage and maintenance within SNS. 

Within NIH, NIAID is the lead agency for early candidate research and 

development for medical countermeasures for biodefense. NIAID issues 

grants and contracts for research on medical countermeasures exploration 

and early development but has no responsibility in taking research 

forward into marketable products. Within OPHEP, the Office of Research 

and Development Coordination (ORDC) has the primary responsibility for 

contracting with industry for the large-scale manufacturing of licensable 

products, including vaccines, for delivery into SNS. Distinct from 

development contracts, ORDC production contracts typically require the

submission of a formal request for FDA product licensing, license 

supplements, long-term maintenance of the stockpiled products, and a 

long-term manufacturing base to continue replenishing the stockpile as 

product expires. 

 3

Merck Sharp & Dhome is a subsidiary of Merck & Co., Inc. 

4

Anthrax infection has occurred most commonly in settings like wool mills, where workers

may be exposed to infected animal products. 

5

Before FDA was established as the licensing authority for vaccines, NIH performed that 

function. 

Page 7 GAO-06-756T 
Through the Center for Biologics Evaluation and Research (CBER), FDA

licenses biological products, which include vaccines, and the facilities they 

are produced in. Manufacturers are required to comply with current good

manufacturing practices regulations, which regulate personnel, buildings,

equipment, production controls, records, and other aspects of the vaccine 

manufacturing process.6

The Characteristics and 

Development of Vaccines 

Vaccines have three distinguishing features that contrast with those of 

chemical drugs. First, either they have no clearly chemically defined 

composition or simple chemical analysis is insufficient for their effective 

characterization. Second, they are properly evaluated, qualitatively or 

quantitatively, usually by measuring their effects in the living organism. 

Third, quality can be guaranteed not from final tests on random samples 

but only from a combination of in-process tests, end-product tests, and 

strict controls of the entire manufacturing process. 

The quality of a vaccine is closely linked to its manufacturing process, 

which must be rigorously controlled to ensure that batches of vaccines 

produced at different times are reproducible and consistent in quality. In 

general, quality is achieved by applying the current good manufacturing 

practice. This process is not static but involves manufacturers and 

regulators in continuing assessment and upgrades as scientific progress, 

technical development, and experience help identify deficiencies and 

make improvements possible. Such principles also apply to the 

manufacturing facilities and equipment. Accordingly, vaccine production 

is very highly regulated to ensure that the products are consistent in 

quality and safe and effective for the purposes for which regulatory 

approval was granted. 

The development of a vaccine is similar to the development of drugs and 

other immunizing agents. A sponsor who has developed a candidate 

vaccine and wishes to begin clinical trials with human subjects must 

submit an investigational new drug (IND) application to FDA.7

 This starts 

 6

The regulations embody a set of scientifically sound methods, practices, or principles that 

are implemented and documented during development and production to ensure the 

consistent manufacture of safe, pure, and potent products. Such principles apply to the

manufacturing process as well as to the facilities products are manufactured in. (21 C.F.R., 

parts 600 through 680.) 

7

An IND application is a request for authorization from FDA to administer an

investigational drug or biological product to humans. 

Page 8 GAO-06-756T 
an official oversight process of formal studies, regulated by CBER within 

FDA, typically composed of three phases of clinical trials involving an

increasing number of human subjects.8

 Phase 1 trials are safety and 

immunogenicity studies performed in 20 to 100 healthy, volunteer 

subjects. Phase 2 studies, which may involve hundreds of subjects, take an 

in-depth look at the effectiveness of the drug and may include analysis of 

dose ranges and dose regimens. Finally, Phase 3 trials typically involve 

thousands of individuals and provide the documentation of effectiveness 

and important additional safety data required for licensing. At any stage of

the clinical or animal studies, if the data raise significant concerns about 

either safety or effectiveness, FDA may request additional information or 

studies or may halt ongoing clinical studies. Clinical trials typically last 

6 years. 

After successful completion of all three phases, the sponsor submits a 

biologics license application for FDA’s review and approval. The proposed 

manufacturing facility is inspected during this stage, and production of the 

vaccine as it is in progress is examined in detail. This FDA review process 

can take several years, depending on the product.

To ensure continuing safety, FDA oversees the manufacturing process for 

as long as the manufacturer holds a license for the product. According to 

industry sources, the challenge in scaling up vaccine production from a 

research laboratory to a large manufacturing environment while still 

maintaining quality requires much skill, sophisticated facilities, and a great

deal of experience. 

The federal agencies involved in the response in the postal facilities had 

differing responsibilities. CDC and state and local health departments 

primarily provided public health advice and assistance to USPS. CDC has 

had primary responsibility for national surveillance of specific diseases, 

including anthrax; it has also conducted epidemiologic investigations to 

determine, among other things, the source of the disease. The Federal 

Bureau of Investigation (FBI) has been responsible for criminal 

Anthrax Detection in 

Postal Facilities and 

the Federal Role 

 8

In May 2002, FDA published Approval of Biological Products When Human Efficacy

Studies Are Not Ethical or Feasible (21 C.F.R. 601, Subpart H, as well as 21 C.F.R. 314,

Subpart I for New Drugs). This rule, known as the “Animal Rule,” permits the substitution 

of animal studies for human trials where human efficacy studies are not ethical and field 

trials are not feasible, provided a scientifically valid animal model for the disease exists.

This rule does not obviate the need for safety data, which must still be established. 

Page 9 GAO-06-756T 
investigations involving interstate commerce and the mail and crimes 

committed on federal property. EPA has been the nation’s lead agency for

responding to a release of hazardous substances into the environment. 

Responding to health emergencies, including bioterrorist attacks, is 

generally a local responsibility, but localities could and did request CDC’s 

assistance in fall 2001. CDC performed the tests needed to confirm cases 

of anthrax and analyzed the substances in the two contaminated letters 

recovered in New York City. The Agency for Toxic Substances and 

Disease Registry and the National Institute for Occupational Safety and 

Health within CDC helped USPS conduct environmental tests of some of 

its facilities and advised USPS on its facilities’ decontamination. 

USAMRIID has conducted basic and applied research in the diagnosis, 

treatment, and prevention of hazardous infectious diseases for the 

military. It analyzed some environmental samples from postal facilities. It 

also performed detailed analyses, for the FBI, of anthrax spores in the 

letters addressed to Senators Tom Daschle and Patrick Leahy. The 

Occupational Safety and Health Administration, responsible for employee 

health and safety issues, provided technical assistance and guidance to

USPS on the decontamination of postal facilities. 

The response to the incident in the American Media Incorporated building 

in Florida in September 2001 led to the identification of mail as the 

potential source of contamination; eventually, it led to the sampling of the 

postal facilities. The agencies began sampling on October 12, 2001, in 

Florida and stopped on April 21, 2002, when the Wallingford, Connecticut, 

facility was sampled for the last time. 

On October 8, 2001, the President created the Office of Homeland Security 

to develop and coordinate a comprehensive national strategy for dealing

with domestic terrorist threats or attacks. The office, which had limited 

involvement in the 2001 response, was superseded by the Homeland 

Security Act of 2002, which transferred many of its functions to DHS. DHS, 

which became operational in 2003, was created by combining many 

previously separate agencies. It is assigned the lead role in coordinating 

the efforts of federal agencies that respond to acts of terrorism in the 

United States. 

Page 10 GAO-06-756T 
As you know, the agencies that sampled postal facilities in 2001—USPS, 

CDC, and EPA—did not use validated sample collection and analysis 

methods to perform their tests. According to these agencies, validated 

methods were not available at that time. They conducted several 

interdependent activities, including sample strategy development, 

followed by sample collection, transportation, and analysis of the samples 

to detect anthrax. Neither these activities nor the overall process had been 

validated for anthrax testing. 

Agency Sampling 

Detection Methods 

Were Not Validated 

Validation is a formal, empirical process in which an authority determines

and certifies the performance characteristics of a given method. 

Therefore, investments are also needed to validate these methods, as well 

as the overall anthrax detection process. Validating the overall process is 

important because operational and health-related decisions are made on

the basis of testing results that the process generates. 

CDC and USPS officials said that they used targeted sampling; that is, they

collected samples from specific areas considered—based on agencies’ 

technical judgments—more likely to be contaminated. Such judgments can 

be effective in some situations, for example, in determining the source of

contamination in a disease outbreak investigation, provided results are 

positive. However, if the results are negative, the basic question—Is this 

building contaminated?—cannot be answered with statistical confidence.

When the level of contamination is extremely high and dispersed in a 

facility, the method of sampling (for example, wipes versus swabs) may 

not be as critical if the purpose is to find some contaminant. However, at 

lower levels, a way of interpreting negative results is needed, and this 

requirement emphasizes the importance of the validation of the methods 

and the need for statistically based sampling strategies. This emphasizes 

the need for methods that have been validated and sampling strategies that 

are likely to find contamination at low levels. Probability-based sampling 

does allow conclusions at specific levels of confidence about testing 

results. 

Using a probability-based sampling strategy, together with validated 

methods for detecting contamination, would provide a known level of 

confidence with which to interpret any negative results. This would allow 

agencies to be more definitive in determining necessary actions. Figure 1 

shows how lack of validation could affect individual activities—which 

include the sampling strategy—as well as the results generated by the 

overall process. 

Page 11 GAO-06-756T 
Figure 1: Lack of Validation Can Affect Individual Activities and the Overall Process 

The lack of validated methods for assessing contamination in postal 

facilities impeded the agencies in responding to the incidents. The 

significance of the lack of validated methods was exemplified in the case 

of the one postal facility, where negative preliminary results were obtained 

by field-based methods of analysis, with limitations that appear to have 

been not well understood by some agencies. Negative results do not 

necessarily mean a facility is free from contamination. As we reported, 

results can be negative if (1) samples were not collected from places 

where anthrax was present, (2) the detection limit of the method was 

greater than the actual contamination level, (3) not enough samples were 

recovered from the sample material, (5) analysis of the sample extract did

not detect spores, or (6) anthrax was not present in the facility. 

Page 12 GAO-06-756T 
Given the lack of validated methods for detecting anthrax contamination 

in facilities, we recommended that the Secretary of Homeland Security 

develop a coordinated approach to (1) improve the overall process for 

detecting anthrax and (2) increase confidence in negative test results 

generated by that process. This approach would include working with 

agencies to ensure that appropriate validation studies of the overall 

process of sampling activities, including the methods, are conducted. 

Specifically, we recommended that the Secretary

1. take a lead role in promoting and coordinating the activities of the 

various agencies that have the technical expertise related to

environmental testing; 

2. ensure that a definition of validation is developed and agreed on; 

3. guarantee that the overall process of sampling activities, including 

methods, is validated so that performance characteristics, including 

limitations, are clearly understood and results can be correctly

interpreted; 

4. see that appropriate investments are made in empirical studies to 

develop probability-based sampling strategies that take into account 

the complexities of indoor environments. 

When we issued our report, CDC, DHS, and USPS agreed with our 

conclusion—that methods for detecting anthrax contamination in facilities 

were not validated—and with the thrust of our recommendations—calling 

for a coordinated, systematic effort to validate the methods to be used for 

such testing, but they (1) disagreed with or expressed concern about our 

conclusions or the recommendation dealing with targeted versus 

probability sampling, (2) emphasized that validated testing methods for 

anthrax were not available in 2001 and that federal and state organizations 

did the best they could under the circumstances, and (3) identified factors

or issues that need to be considered in validating testing methods. 

Also, at that time, uncertainty over which agency would take the lead role 

in improving the overall process for detecting anthrax, and how studies 

were to be funded, continued after our report was released. DHS stated 

that while it has overall responsibility for coordinating the federal 

response during future biological attacks, EPA had the “primary 

responsibility for establishing the strategies, guidelines, and plans for the 

recovery from a biological attack” while HHS had the lead role for any 

related public health response and guidelines. DHS also stated that it 

Page 13 GAO-06-756T 
coordinated regularly with EPA’s National Homeland Research Center to 

exchange information on research needs and to discuss priorities and gaps 

for a wide range of security-related research areas. DHS stated that it 

would coordinate with EPA to ensure that appropriate investments were 

made to explore improved sampling. Consequently, it was unclear how 

DHS could ensure that appropriate prioritized investments were made for 

all biothreat agents, with respect to agencies other than EPA, and how 

such priorities and gaps would be addressed. 

Concerning our recommendation about probability-based sampling 

strategies, DHS said that it first wanted to develop sampling requirements 

and then evaluate both targeted and probability-based sampling against 

those requirements. While CDC and USPS stated that they agreed with the 

importance of using validated testing methods, they raised various 

concerns about our discussion of targeted versus probability-based 

sampling. 

DHS formally responded to our recommendations on September 19, 2005,

stating that it agreed with them and was taking several actions to address 

them. These actions included working with agencies through interagency

memorandums of understanding, interagency committees, working 

groups, and collaborations, with various federal agencies such as HHS and 

EPA. In particular, a memorandum of understanding for coordinating and 

monitoring biological threat agents among DHS, DOD, HHS, USPS, and the 

Department of Justice was signed on May 9, 2005. Another involved 

several agencies—DOD, EPA, HHS, Justice, and the Department of 

Agriculture, to name a few—and was to establish an integrated consortium 

of laboratory networks. Also, in fiscal year 2005, DHS said it was to 

standardize and validate the method by which hazardous materials 

technicians (for example, first responders) collect, transport, and store 

suspicious powder samples. 

DHS Has Taken Some 

Actions to Implement 

Our 

Recommendations on 

the Validation of 

Sampling Methods 

and Strategies

In preparation for this testimony, we asked USPS, CDC, DHS, and EPA for 

comments regarding actions they have taken to implement our 

recommendations. EPA did not provide us comments. Comments from 

USPS, CDC, and DHS are summarized below. 

USPS, on April 24, 2006, reported to us that it has been assisting DHS to 

implement our recommendations. DHS has asked USPS to become part of 

a subject matter expert team as a result of the real-world experience 

gained during the 2001 anthrax attacks and the subsequent response, 

Page 14 GAO-06-756T 
clean-up, and remediation efforts at a number of mail processing facilities 

and post offices. (For more on USPS’s actions, see app. I.) 

CDC, on May 5, 2006, told us it is taking steps we believe are in the right 

direction. CDC officials told us that CDC has not changed its position on 

using targeted sampling as its primary strategy for initial response 

sampling but is exploring probability-based sampling to augment this 

approach. CDC officials told us that CDC has also developed a program to 

expand its microbiology objectives; the program’s focus areas include

plans for evaluating priority biothreat agents, including anthrax, in a 

variety of media. Further, CDC told us it has completed or has ongoing 

studies on the recovery of Bacillus anthracis spores from various types of 

surfaces. (More on CDC’s actions is in app. II.) 

On May 3, 2006, DHS stated that it 

“concurs with the GAO that use of stratified and probabilistic sampling strategies, together 

with validated methods for detecting contamination, would provide a known level of 

confidence with which to interpret any negative results and would thus enable agencies to

be more definitive in determining necessary actions.” 

DHS reported to us several actions it had taken toward implementing the 

recommendations. (For more on DHS’s actions, see app. III.) 

While we believe that DHS’s individual actions are in the right direction,

DHS needs to develop a formal strategic plan that includes a “roadmap” 

outlining how individual agencies’ efforts would lead to (1) the validation 

of the overall process of sampling activities, including methods, and (2) 

the development of a probability-based sampling strategy that takes into

account the complexities of indoor environments. Such a plan would 

assist DHS in monitoring progress and measuring agency performance 

toward improving the detection of anthrax and other prioritized threat 

agents. 

Starting in 1999, we identified a number of problems with the licensed

anthrax vaccine. These included, among others, (1) the need for a six-shot 

regimen and annual booster shots; (2) questions about the long-term and 

short-term safety of the vaccine, including how safety is affected by gender 

differences; and (3) uncertainty about the vaccine’s efficacy. In addition, 

we provided information on the disadvantages of the licensed vaccine and

the status of federal efforts to develop an improved anthrax vaccine. 

The Licensed Anthrax 

Vaccine Had Several 

Limitations 

Page 15 GAO-06-756T 
The dosing regimen, or protocol, for the licensed anthrax vaccine calls for 

a series of six shots over 18 months. An initial series of three shots is given 

at 2-week intervals, followed by a series of three shots at 6-month 

intervals. Annual boosters are required thereafter. The required six-dose 

schedule and annual boosters complicate the logistics and increase the 

cost of vaccination. At the time of our earlier reports, no studies had been

done on the optimum dosing regimen. Recently, however, CDC has begun 

conducting studies to determine the feasibility of a three-dose schedule. 

FDA would have to review and approve any change in product labeling.9

The long-term safety of the licensed vaccine has not been studied. Data on

the prevalence and duration of short-term reactions to the vaccine are 

limited but suggest that women experience a higher rate of adverse 

reactions, both local and systemic, than men do.

Before the vaccine was licensed, a study on the efficacy of the original 

vaccine concluded that it provided protection to humans against 

cutaneous anthrax. In the 1980s, DOD began testing the efficacy of the 

licensed vaccine on animals, focusing on its protection against inhalation

anthrax. DOD’s studies, while showing some positive results, may not be 

extrapolated to humans until serologic correlates of immunity in an animal

model that can be applied to humans are established. 

According to researchers and the Institute of Medicine of the National 

Academy of Sciences, the licensed anthrax vaccine has several additional

disadvantages.10 The amount of protective antigen in the vaccine varies 

from lot to lot, because the manufacturing process cannot precisely 

quantify the antigen.11 Also, there is some evidence that the current 

anthrax vaccine may have diminished efficacy against certain virulent 

strains of anthrax. 

The licensed vaccine has been given primarily to military personnel. DOD, 

however, has a unique set of requirements, as it has a narrow, relatively

 9

CDC is conducting a wide range of anthrax vaccine research activities, including ensuring

the vaccine’s safety while minimizing the number of doses. 

10P. S. Brachman and A. Friedlander, “Anthrax,” in Vaccines, eds. S. A. Plotkin and E. A.

Mortimer Jr. (Philadelphia: W. B. Saunders Company, 1994), p. 737, and Institute of 

Medicine, Chemical and Biological Terrorism: Research and Development to Improve 

Civilian Medical Response (Washington, D.C.: National Academy Press, 1999), p. 135. 

11Institute of Medicine, Chemical and Biological Terrorism, p. 135.

Page 16 GAO-06-756T 
young, healthy, and homogenous, target population. This reduces many 

problems, although not all, as in the case of reactogenicity by gender. DOD 

requirements also assume a continuous threat for which they require 

preexposure immunization. Civilian populations, in contrast, are much 

more diverse than military populations, and immunization of civilians 

would likely be difficult to justify, based on the available bio-threat 

assessments.

In the late 1980s, DOD research identified a second-generation 

recombinant protective antigen (rPA) anthrax vaccine, created with a 

process that is fully defined, quantified, and controlled in terms of 

protective antigen; that can be developed; and that requires fewer doses.12

DOD research also showed that an rPA anthrax vaccine could be created

with modern techniques to produce highly purified protective antigen. 

This process not only would remove unwanted bacterial proteins but 

would also enable precise amounts of the purified protective antigen to be

incorporated into the vaccine. A further potential benefit was that 

compared to the current vaccine, the protective antigen could be produced 

in a nonspore-forming organism. As a result, according to DOD officials, 

manufacturers could use their buildings and equipment to produce the 

anthrax vaccine as well as other vaccines. 

HHS Has Taken Steps 

to Fund the 

Development of a 

Second-Generation 

Anthrax Vaccine 

In 1995, the USAMRIID developed a pilot lot of a new rPA vaccine against 

anthrax. It has been tested successfully in experiments using animals but 

has not been tested on humans. USAMRIID officials stated that this testing 

would take about 3 years; FDA approval of the manufacturing could take

years longer. In 1999, DOD considered further development of this vaccine 

an unfunded requirement. In response to the perceived threat of 

bioterrorism, HHS’s NIAID formed a working group to develop and test a 

second-generation anthrax vaccine and, accordingly, funded several active 

research grants. 

 12B. Ivins and others, “Immunization Studies with Attenuated Strains of Bacillus 

anthracis,” Journal of Infection and Immunity 52 (1986): 454–58; B. E. Ivins, “The Search

for a New-Generation Human Anthrax Vaccine,” Clinical Immunology Newsletter 9 (1988): 

30–32; and Y. Singh and others, “Study of Immunization against Anthrax with the Purified 

Recombinant Protective Antigen of Bacillus anthracis,” Journal of Infection and

Immunity 66 (1998): 3447–48. 

Page 17 GAO-06-756T 
In September 2002 and September 2003, NIAID awarded contracts to 

develop a new rPA vaccine effective against inhalation anthrax.13 The 

contracts were for developing and testing candidate vaccines, with a 

requirement for evaluating safety, efficacy, and a potential provider’s 

capability for manufacturing the vaccine and achieving FDA licensing. The 

contracts—for $13.6 million in 2002 and $80.3 million in 2003—were 

awarded to VaxGen Inc., a California-based biopharmaceutical company.14

The 2002 RFP called for developing, manufacturing, characterizing, and 

evaluating pilot lots of an rPA anthrax vaccine developed under conditions 

necessary to support the product’s use as an investigational new drug. The 

2003 RFP built on the 2002 work and was to further develop a vaccine 

candidate suitable for commercial-scale manufacturing that demonstrated 

safety and immunogenicity in clinical and animal studies. 

The stated objectives in these two RFPs addressed some of the problems 

we identified with the licensed vaccine, including our recommendation. 

First, they required the development of a recombinant vaccine. As noted, 

DOD research showed that modern recombinant techniques could 

produce a vaccine that would contain highly purified and precise amounts 

of protective antigen, thereby reducing lot-to-lot variation, whose 

disadvantage was noted with the licensed anthrax vaccine. 

Second, as we reported, the six-dose, 18-month immunization regimen, 

followed by annual booster shots, was problematic. In the 2002 RFP, 

NIAID required that the rPA candidate vaccines be administered in not 

more than three doses. 

We also reported that the long-term safety of the licensed vaccine had not 

been studied and that data on short-term reactions, although limited, 

suggested that women experience a higher rate of adverse reactions, both 

local and systemic, than men do. NIAID requirements in the two 

development RFPs included Phase I and Phase II clinical trials to evaluate

short-term safety, but neither RFP included analysis of gender differences.

In discussions with company officials, however, VaxGen has stated that it

 13The RFP for the 2002 contract was NIH-NIAID-DMID-02-26; for the 2003 contract, NIHNIAID-DMID-03-29. 

14For the 2002 RFP, two awards totaling $22.5 million were given—$13.6 million to VaxGen

and $8.9 million to Avecia Ltd. of Manchester, England.

Page 18 GAO-06-756T 
included both male and female subjects in its clinical trials and is 

examining this issue. 

An issue that remains outstanding, however, is that long-term safety 

studies have not been conducted or required before making awards for full 

procurement. 

We also found that because terrorist events would be likely to occur with 

little or no warning, postexposure immunization capability would be 

beneficial. A stated objective in the 2002 RFP was to investigate candidate

vaccines that would provide protection when administered both before 

exposure and in a postexposure immunization regimen, when combined 

with antibiotics. 

NIAID has taken steps to anticipate downstream, large-scale 

manufacturing issues by requiring a feasibility plan for the manufacture 

and delivery of 25 million doses in the 2002 contract and, in the 2003 

contract, the actual delivery of 3 million to 5 million doses of rPA anthrax 

vaccine from at least three consistency lots, following good manufacturing 

practices. The 2003 RFP also included objectives to develop and validate 

product release and characterization criteria to support eventual 

submission to FDA for licensing. 

In November 2004, in the first contract under Project Bioshield, ORDC 

awarded VaxGen a contract for $877.5 million for the manufacture and 

delivery of 75 million doses of rPA anthrax vaccine in prefilled syringes for 

SNS. Among other things, the contract requires VaxGen to obtain FDA 

licensure for both preexposure use and postexposure use with antibiotics, 

and the initiation and completion of special population clinical trials, 

including pediatric and geriatric populations. 

HHS’s Procurement 

Strategy Is Very 

Aggressive 

In the RFP for the contract, ORDC stated that the urgent nature of the 

current threat required an accelerated pace of development, testing, 

approval, and procurement of the vaccine and anticipated that it would 

have to be administered under a “contingency use” 

IND protocol, held by CDC, if needed, prior to licensure by FDA. However, 

the RFP also specified that all vaccine manufactured and acquired under 

the contract must meet the regulatory deliverables as required for 

licensure. 

Page 19 GAO-06-756T 
The normal schedule for taking a vaccine from preclinical studies to 

licensure varies, depending on what is known about both the specific 

nature of the infectious disease and the planned application of the vaccine 

in terms of when and on whom the vaccine is to be used. These factors can 

prolong the development of a vaccine as long as 15 years (for civilian use) 

or as short as 8 years (for military use). Because of the U.S. government’s 

stated need for a vaccine that can counter a domestic biothreat against 

civilian populations, HHS has undertaken an aggressive procurement of a 

vaccine on a very short schedule. 

The NIAID development and test contracts, whose purpose was 

presumably to aid in making the best procurement award decision, are not 

yet completed and, in fact, overlap to a great degree with the procurement 

contract. At the time the full procurement contract was awarded in 

November 2004, the initial 2002 development contract to study the basic

safety and immunogenicity of candidate vaccines was still ongoing, and 

the 2003 contract was only part way through Phase II clinical trials. In fact,

today, neither the 2002 nor the 2003 contract—intended to ensure a 

candidate vaccine with appropriate characteristics and a provider’s 

manufacturing capability sufficient for licensing and successful delivery—

has yet been completed, only 6 months before first delivery of 25 million 

doses of SNS-ready product is required. HHS officials acknowledge that 

the procurement contract’s milestones are very aggressive and agree that 

the contract contains little to no provision for slippage. Additionally, the 

procurement contract is fixed-price and specifies that no payment will be 

made before delivery. The financial burden is fully on the contractor 

should additional costs arise because of an unexpected slip in schedule. 

In conclusion, a contract schedule with no margin for error, especially for 

vaccine development, which is known to be risky, is not conducive to 

building confidence that a vaccine will be available for use within the 

arbitrarily defined time period. While the government should not pay out

money to a contractor unless and until it has met the terms of its contract,

contractors that do not have the resources to assume such risk will not be 

able to meet the contract requirements, thus limiting the pool of 

companies that are capable of meeting the nation’s needs. 

While the government should be a tough negotiator when contracting for 

major procurements, it is important to understand the unique issues at 

stake in this early phase of implementation of the biodefense strategy. The 

rest of the biotechnology sector will be watching to see whether the 

industry and the U.S. government can make this partnership work. Issues 

with this contract might have an effect beyond just this individual vaccine

Page 20 GAO-06-756T 
procurement. They could have an impact on how the biotechnology 

industry responds to government overtures in the future for the 

development and procurement of medical countermeasures for the many 

biothreat agents still to be addressed. 

Mr. Chairman, this concludes my prepared remarks. I would be happy to 

respond to any questions that you or other members of the subcommittee 

may have at this time. 

For further information regarding this statement, please contact 

Keith Rhodes at (202) 512-6412, or rhodesk@gao.gov, or Sushil K. Sharma, 

Ph.D., Dr.PH,, at (202) 512-3460, or sharmas@gao.gov. Contact points for 

our Offices of Congressional Relations and Public Affairs may be found on

the last page of this statement. Hazel Bailey, William Carrigg, 

Barbara Chapman, Crystal Jones, Penny Pickett, and Elaine Vaurio made 

key contributions to this statement. 

Contacts and 

Acknowledgments 

Page 21 GAO-06-756T 
Abbreviations 

AVA anthrax vaccine adsorbed 

AVRP Anthrax Vaccine Research Program 

AVST Anthrax Vaccine Safety Team 

CBER Center for Biologics Evaluation and Research 

CDC Centers for Disease Control and Prevention 

DHS Department of Homeland Security 

DOD Department of Defense 

EPA Environmental Protection Agency 

FBI Federal Bureau of Investigation 

FDA Food and Drug Administration 

HHS Department of Health and Human Services 

IND investigational new drug 

NIAID National Institute of Allergy and Infectious Diseases 

NIH National Institutes of Health 

OPHEP Office for Public Health Emergency Preparedness

ORDC Office of Research and Development Coordination 

rPA recombinant protective antigen 

SDST Subcommittee of Decontamination Standards Technology 

SNS Strategic National Stockpile 

USAMRIID U.S. Army Medical Research Institute of Infectious

 Diseases 

USPS United States Postal Service 

Page 22 GAO-06-756T 
Page 23 GAO-06-756T 

Appendix I: United States Postal Service 

Initiatives 

U.S. Postal Service (USPS) officials reported to us these activities in 

responding to our recommendations: 

On the recommendation addressed to the Department of Homeland 

Security (DHS) to develop appropriate validation studies of various 

activities in detecting anthrax: 

• USPS has been helping DHS implement that recommendation. It has been

working with its federal partners to further examine existing biological

coordination and protocol efforts, within the National Capital Region. 

• USPS is also working with state and local public health departments by 

participating in several biological working groups chartered to help clarify 

and reduce variance in procedures and protocols and, per GAO’s 

recommendations, to develop validation procedures to help ensure that 

biothreat test results are reliable and can be clearly understood and 

correctly interpreted. 

• DHS has asked USPS to become part of a subject matter expert team as a 

result of the real-world experience USPS gained in the 2001 anthrax 

attacks, its response, and its cleanup and remediation efforts at a number

of mail processing facilities and post offices. 

• USPS was asked to help develop and implement the guidance as part of 

the National Capital Region BioWatch Advisory Council. 
Page 24 GAO-06-756T 

Appendix II: Centers for Disease Control and 

Prevention Initiatives 

Centers for Disease Control and Prevention (CDC) officials reported 

information on their work on anthrax detection and anthrax vaccine. With

respect to anthrax detection, CDC said it is developing a probabilistic 

sampling approach. This project will augment the targeted sampling 

approach that it uses for initial response sampling. CDC officials told us 

that CDC is “exploring the need for probability sampling in those instances 

when statistical inferences are necessary.” 

CDC has also developed a program that will expand its environmental 

microbiology objectives. This program has several focus areas. One is 

identifying priority agents, through sampling strategy development, sample 

collection, sample transportation, and sample analysis. Another is risk 

reduction activities, such as determining the risk of infection and 

evaluating techniques and procedures for reducing risk, including 

improving decontamination methods. 

Further, CDC has completed studies and has studies in progress on the 

recovery of Bacillus anthracis spores from various types of surfaces using 

different collection methods, including macrofoam swabs, wipes, and 

HEPA vacuum. It also plans to study the survival rates of other biothreat 

agents on nonporous surfaces and to evaluate HEPA-vacuum samples for 

microbial analysis. 

The National Immunization Program and the National Center for 

Infectious Diseases components of the proposed National Center for 

Immunization and Respiratory Diseases appreciated the opportunity to 

share information about the status of CDC’s Anthrax Vaccine Research 

Program. 

In 1999, CDC received funding to conduct studies of the safety and 

efficacy of the U.S. licensed anthrax vaccine—anthrax vaccine adsorbed 

(AVA). CDC’s Anthrax Vaccine Research Program (AVRP) consists of a 

human clinical vaccine trial with quantitative primary serological 

endpoints, corroborative antibody functional analyses, and an 

immunological correlates of protection study in rhesus macaques. 

The focus of AVRP is a large-scale, multicenter, Phase III human clinical 

trial with 1,564 participants. The study’s objective is to optimize the use of

AVA, the only licensed anthrax vaccine in the United States.1

 The study 

 1

AVA, or BioThrax, is licensed to BioPort Corporation, Lansing, Michigan. 
evaluates the potential for changing the route of administration, reducing

the number of primary series vaccinations for the licensed vaccine, and 

improving the profile of side effects. A successful conclusion to the study 

will double the availability of AVA, increase vaccine acceptance and 

uptake because of a reduction in side effects, and provide animal study 

data demonstrating long-term protection against inhalation anthrax 

afforded by a priming series of three intramuscular injections. 

Analysis of the human clinical trial serological and reactogenicity data at

an intermediate stage in the study showed that it is possible to drop the 

dose at week two, change the route of administration to intramuscular, 

and reduce side effects without making an impact on antibody responses 

to a priming series of three injections. The interim report was submitted to 

the Food and Drug Administration (FDA) in February 2005, and 

subsequently the vaccine manufacturer filed a supplement to its biologics 

license application to add this new regimen. 

The AVRP’s remaining research goals are to confirm that two additional 

doses can be dropped from the priming series at 12 months and 18 months, 

thus moving to a three- injection intramuscular regimen; to adopt biennial 

rather than annual boosters; and to establish in nonhuman primate models 

the onset and duration of the protection of the three-dose intramuscular 

regimen (the “correlates of protection” study). 

CDC’s Anthrax Vaccine Safety Team (AVST) is conducting a wide range of 

anthrax vaccine safety research activities critical to accomplishing the 

objectives in CDC’s 1999 congressional mandate. These activities’ goals 

are to (1) address important anthrax vaccine safety questions, (2) build an 

infrastructure to ensure the anthrax vaccine’s safety, (3) build a system to 

address concerns regarding vaccine safety and aid in resolving potential

liability questions, and (4) optimize the vaccination schedule and the 

vaccine’s administration to ensure its efficacy while minimizing the 

number of doses required, reducing the occurrence of adverse events, and 

maximizing the availability of the only licensed anthrax vaccine in the 

United States. 

In collaboration with the Army Medical Surveillance Activity of the 

Department of Defense (DOD) and FDA, CDC established the Vaccine 

Analytic Unit in 2003 on the Walter Reed Army Medical Center Campus. It 

uses data from the Defense Medical Surveillance System to assess whether 

specific longer-term adverse events are associated with AVA and other 

biodefense vaccines; this system is a unique source of active surveillance 

data containing medical, vaccination, and deployment histories for U.S. 

Page 25 GAO-06-756T 
military personnel. The Vaccine Analytic Unit’s research agenda for 

investigating potential AVA adverse events and an AVA study on optic 

neuritis are in press, and a multiple near-concurrent immunization study 

has been completed. Funded studies include evaluations of AVA and 

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis, connective

tissues diseases, diabetes mellitus, Guillain–Barré Syndrome, and atrial 

fibrillation 

Studies to assess the possible effects of AVA on health-related quality of 

life and the role of hormones as the basis for adverse AVA events 

occurring more frequently in women are ongoing in participants of CDC’s 

AVRP, begun in 2002 for administering AVA to workers occupationally at

high risk for exposure to Bacillus anthracis. Also, AVST has ongoing 

collaborative research studies with CDC’s Immunization Safety Office, 

FDA, and DOD to enhance AVA adverse event surveillance and improve 

AVA acceptability. 

Page 26 GAO-06-756T 
Page 27 GAO-06-756T 

Appendix III: Department of Homeland 

Security Initiatives 

Department of Homeland Security (DHS) officials reported the following 

activities to us in addressing our recommendations: 

DHS has taken a lead role in promoting and coordinating the activities of 

various agencies that have technical expertise related to environmental 

testing. DHS 

• led the formulation of a memorandum of understanding among DHS, DOD, 

the Department of Health and Human Services (HHS), and USPS on 

coordinated monitoring of biological threat agents and is leading the 

execution of the memorandum; 

• is leading an effort to establish an Integrated Consortium on Laboratory 

Networks; 

• has established a Federal Postal and Shipping Integrated Project Team; 

• is co-chairing the Subcommittee of Decontamination Standards 

Technology (SDST); 

• is co-sponsoring the Second (and First) National Conference on 

Environmental Sampling for Bio-Threat Agents. 

DHS has adopted the International Quality Management Standard 

definition of validation.

DHS has developed a process to standardize and validate methods; it 

• has validated a method for sampling suspicious powders and 

• is developing a method for the validation of public health actionable 

assays. 

DHS has invested in both targeted and probabilistic sampling strategies 

and in methodologies that are appropriate for monitoring facilities and 

that apply to wide-area and facility restoration. Its research and 

development efforts include 

• performance characterization of three sampling methods on varied 

surfaces; 

• developing the Building Restoration Operations Optimization Model; 
• sponsoring the Visual Sample Module; 

• developing Annotated Characterization and Clearance Sampling Plan 

Templates for preplanning the response to a biological facility attack; 

• developing BioWatch Preparedness and Response Guidance, which 

includes Part III: BioWatch Environmental Sampling; 

• developing native air sample collection strategies and protocols associated

with transportation facilities. 

DHS has prioritized investments for high-risk biological agents through 

internal and interagency coordination, to include

• SDST research and development investment strategy; 

• agency-to-agency discussions on leveraging research and development 

opportunities; 

• internal strategic planning and requirements generation. 

Page 28 GAO-06-756T (460580) 
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