Anthrax: Federal Agencies Have Taken Some Steps to Validate	 
Sampling Methods and to Develop a Next-Generation Anthrax Vaccine
(09-MAY-06, GAO-06-756T).					 
                                                                 
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		 
probability-based 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 short-term 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.					 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-06-756T					        
    ACCNO:   A53639						        
  TITLE:     Anthrax: Federal Agencies Have Taken Some Steps to       
Validate Sampling Methods and to Develop a Next-Generation	 
Anthrax Vaccine 						 
     DATE:   05/09/2006 
  SUBJECT:   Anthrax						 
	     Bioterrorism					 
	     Counterterrorism					 
	     Disease control					 
	     Disease detection or diagnosis			 
	     Emergency preparedness				 
	     Emergency response 				 
	     Federal procurement				 
	     Interagency relations				 
	     Policy evaluation					 
	     Public health preparedness and response		 
	     for bioterrorism program				 
                                                                 
	     Statistical methods				 
	     Strategic planning 				 
	     Vaccination					 
	     Public/private partnerships			 

******************************************************************
** This file contains an ASCII representation of the text of a  **
** GAO Product.                                                 **
**                                                              **
** No attempt has been made to display graphic images, although **
** figure captions are reproduced.  Tables are included, but    **
** may not resemble those in the printed version.               **
**                                                              **
** Please see the PDF (Portable Document Format) file, when     **
** available, for a complete electronic file of the printed     **
** document's contents.                                         **
**                                                              **
******************************************************************
GAO-06-756T

     

     * The History and Nature of Anthrax and the Anthrax Vaccine
     * Anthrax Vaccine and the Federal Role
     * The Characteristics and Development of Vaccines
     * Order by Mail or Phone

Testimony before the Subcommittee on National Security, Emerging Threats
and International Relations, Committee on Government Reform, House of
Representatives

United States Government Accountability Office

GAO

For Release on Delivery Expected at 2:00 p.m. EDT

Tuesday, May 9, 2006

ANTHRAX

Federal Agencies Have Taken Some Steps to Validate Sampling Methods and to
Develop a Next-Generation Anthrax Vaccine

Statement of Keith Rhodes, Chief Technologist, Center for Technology and
Engineering, Applied Research and Methods

GAO-06-756T

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 responsibility for
coordinating federal responses to national incidents of chemical,
biological, radiological, and nuclear material release.

1For 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).

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.

                                Results in Brief

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.

2The 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.

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.

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
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 second-generation
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, 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.

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.

3Merck Sharp & Dhome is a subsidiary of Merck & Co., Inc.

4Anthrax infection has occurred most commonly in settings like wool mills,
where workers may be exposed to infected animal products.

5Before FDA was established as the licensing authority for vaccines, NIH
performed that function.

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 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.

6The 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.)

7An IND application is a request for authorization from FDA to administer
an investigational drug or biological product to humans.

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.

          Anthrax Detection in Postal Facilities and the Federal Role

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
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.

8In 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.

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.

              Agency Sampling Detection Methods Were Not Validated

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.

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.

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.

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
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.

DHS Has Taken Some Actions to Implement Our Recommendations on the Validation of
                        Sampling Methods and Strategies

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.

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, 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.

              The Licensed Anthrax Vaccine Had Several Limitations

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 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
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.

9CDC 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.

HHS Has Taken Steps to Fund the Development of a Second-Generation Anthrax
                                    Vaccine

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.

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.

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
included both male and female subjects in its clinical trials and is
examining this issue.

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

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.

                 HHS's Procurement Strategy Is Very Aggressive

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.

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.

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 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.

                          Contacts and Acknowledgments

For further information regarding this statement, please contact Keith
Rhodes at (202) 512-6412, or [email protected] , or Sushil K. Sharma, Ph.D.,
Dr.PH,, at (202) 512-3460, or [email protected] . 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.

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

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:

           o  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.

           o  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.

           o  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.

           o  USPS was asked to help develop and implement the guidance as
           part of the National Capital Region BioWatch Advisory Council.

           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 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. 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-Barre 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.

           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

           o  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;

           o  is leading an effort to establish an Integrated Consortium on
           Laboratory Networks;

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

           o  is co-chairing the Subcommittee of Decontamination Standards
           Technology (SDST);

           o  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

           o  has validated a method for sampling suspicious powders and

           o  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

           o  performance characterization of three sampling methods on
           varied surfaces;

           o  developing the Building Restoration Operations Optimization
           Model;

           o  sponsoring the Visual Sample Module;

           o  developing Annotated Characterization and Clearance Sampling
           Plan Templates for preplanning the response to a biological
           facility attack;

           o  developing BioWatch Preparedness and Response Guidance, which
           includes Part III: BioWatch Environmental Sampling;

           o  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

           o  SDST research and development investment strategy;

           o  agency-to-agency discussions on leveraging research and
           development opportunities;

           o  internal strategic planning and requirements generation.

           The Government Accountability Office, the audit, evaluation and
           investigative arm of Congress, exists to support Congress in
           meeting its constitutional responsibilities and to help improve
           the performance and accountability of the federal government for
           the American people. GAO examines the use of public funds;
           evaluates federal programs and policies; and provides analyses,
           recommendations, and other assistance to help Congress make
           informed oversight, policy, and funding decisions. GAO's
           commitment to good government is reflected in its core values of
           accountability, integrity, and reliability.

           The fastest and easiest way to obtain copies of GAO documents at
           no cost is through GAO's Web site ( www.gao.gov ). Each weekday,
           GAO posts newly released reports, testimony, and correspondence on
           its Web site. To have GAO e-mail you a list of newly posted
           products every afternoon, go to www.gao.gov and select "Subscribe
           to Updates."

           The first copy of each printed report is free. Additional copies
           are $2 each. A check or money order should be made out to the
           Superintendent of Documents. GAO also accepts VISA and Mastercard.
           Orders for 100 or more copies mailed to a single address are
           discounted 25 percent. Orders should be sent to:

           U.S. Government Accountability Office 441 G Street NW, Room LM
           Washington, D.C. 20548

           To order by Phone: Voice: (202) 512-6000 TDD: (202) 512-2537 Fax:
           (202) 512-6061

           Contact:

           Web site: www.gao.gov/fraudnet/fraudnet.htm E-mail:
           [email protected] Automated answering system: (800) 424-5454 or
           (202) 512-7470

           Gloria Jarmon, Managing Director, [email protected] (202) 512-4400
           U.S. Government Accountability Office, 441 G Street NW, Room 7125
           Washington, D.C. 20548

           Paul Anderson, Managing Director, [email protected] (202)
           512-4800 U.S. Government Accountability Office, 441 G Street NW,
           Room 7149 Washington, D.C. 20548

Appendix II: Centers for Disease Control and Prevention Initiatives

1AVA, or BioThrax, is licensed to BioPort Corporation, Lansing, Michigan.

Appendix III: Department of Homeland Security Initiatives

(460580)

This is a work of the U.S. government and is not subject to copyright
protection in the United States. It may be reproduced and distributed in
its entirety without further permission from GAO. However, because this
work may contain copyrighted images or other material, permission from the
copyright holder may be necessary if you wish to reproduce this material
separately.

GAO's Mission

Obtaining Copies of GAO Reports and Testimony

Order by Mail or Phone

To Report Fraud, Waste, and Abuse in Federal Programs

Congressional Relations

Public Affairs

transparent illustrator graphic

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 [email protected].

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

May 9, 2006

ANTHRAX

Federal Agencies have taken Some Steps to Validate Sampling Methods and to
Develop a Next Generation Anthrax Vaccine

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 probability-based 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 short-term
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.

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.

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.
*** End of document. ***