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Report to Congressional Requesters:
United States Government Accountability Office:
GAO:
September 2009:
High-Containment Laboratories:
National Strategy for Oversight Is Needed:
GAO-09-574:
GAO Highlights:
Highlights of GAO-09-574, a report to congressional requesters.
Why GAO Did This Study:
U.S. laboratories working with dangerous biological pathogens (commonly
referred to as high-containment laboratories) have proliferated in
recent years. As a result, the public is concerned about the oversight
of these laboratories. The deliberate or accidental release of
biological pathogens can have disastrous consequences.
GAO was asked to determine (1) to what extent, and in what areas, the
number of high-containment laboratories has increased in the United
States, (2) which federal agency is responsible for tracking this
expansion and determining the associated aggregate risks, and (3)
lessons learned from highly publicized incidents at these laboratories
and actions taken by the regulatory agencies.
To carry out its work, GAO surveyed and interviewed federal agency
officials, (including relevant intelligence community officials),
consulted with experts in microbiology, reviewed literature, conducted
site visits, and analyzed incidents at high-containment laboratories.
What GAO Found:
The recent expansion of high-containment laboratories in the United
States began in response to the need to develop medical countermeasures
after the anthrax attacks in 2001. Understandably, the expansion
initially lacked a clear, governmentwide coordinated strategy. In that
emergency situation, the expansion was based on individual agency
perceptions of the capacity their high-containment labs required as
well as the availability of congressionally approved funding. Decisions
to fund the construction of high-containment labs were made by multiple
federal agencies in multiple budget cycles. Federal and state agencies,
academia, and the private sector considered their individual
requirements, but an assessment of national needs was lacking. Even
now, after more than 7 years, GAO was unable to find any projections
based on a governmentwide strategic evaluation of future capacity
requirements set in light of existing capacity; the numbers, location,
and mission of the laboratories needed to effectively counter
biothreats; and national public health goals. Such information is
needed to ensure that the United States will have facilities in the
right place with the right specifications.
Furthermore, since no single agency is in charge of the expansion, no
one is determining the aggregate risks associated with this expansion.
As a consequence, no federal agency can determine whether high-
containment laboratory capacity may now meet or exceed the national
need or is at a level that can be operated safely. If an agency were
tasked, or a mechanism were established, with the purpose of overseeing
the expansion of high-containment laboratories, it could develop a
strategic plan to (1) ensure that the numbers and capabilities of
potentially dangerous high-containment laboratories are no greater than
necessary, (2) balance the risks and benefits of expanding such
laboratories, and (3) determine the type of oversight needed.
Four highly publicized incidents in high-containment laboratories, as
well as evidence in scientific literature, demonstrate that (1) while
laboratory accidents are rare, they do occur, primarily due to human
error or systems (management and technical operations) failure,
including the failure of safety equipment and procedures, (2) insiders
can pose a risk, and (3) it is difficult to control inventories of
biological agents with currently available technologies. Taken as a
whole, these incidents demonstrate failures of systems and procedures
meant to maintain biosafety and biosecurity in high-containment
laboratories. For example, they revealed the failure to comply with
regulatory requirements, safety measures that were not commensurate
with the level of risk to public health posed by laboratory workers and
pathogens in the laboratories, and the failure to fund ongoing facility
maintenance and monitor the operational effectiveness of laboratory
physical infrastructure.
Oversight plays a critical role in improving biosafety and ensuring
that high-containment laboratories comply with regulations. However,
some aspects of the current oversight programs provided by the
Departments of Health and Human Services and Agriculture are dependent
upon entities monitoring themselves and reporting incidents to federal
regulators. Since 2001, personnel reliability programs have been
established to counter insider risks, but their cost, effectiveness,
and impact has not been evaluated.
What GAO Recommends:
GAO is recommending that (1) the National Security Advisor name an
entity charged with government-wide strategic evaluation of high-
containment laboratories and (2) the Secretaries of Health and Human
Services and Agriculture address specific oversight issues regarding
high-containment laboratories. The Secretaries of Health and Human
Services and Agriculture agreed with our recommendations relevant to
them.
View GAO-09-574 or key components. For more information, contact Nancy
Kingsbury at (202) 512-2700 or kingsburyn@gao.gov.
[End of section]
Contents:
Letter:
Background:
The Number of BSL-4 and BSL-3 Laboratories and Their Workforce Is
Increasing in Different Sectors throughout the United States:
No Federal Agency Has the Mission to Track the Expansion of All High-
Containment Laboratories and Regulate Biosafety in the United States:
Lessons Learned from Four Incidents Highlight the Risks Inherent in the
Expansion of High-Containment Laboratories:
Conclusions:
Recommendations for Executive Action:
Agency Comments and Our Evaluations:
Appendix I: Scope and Methodology:
Appendix II: Expert Panel:
Appendix III: List of Select Agents and Toxins as of November 17, 2008:
Appendix IV: Biological Agents Recommended for BSL-3 Containment That
Are Not Select Agents:
Appendix V: The Army's Requirements for High-Containment Laboratories
in 2001:
Appendix VI: CDC's Integrated Approach to Biocontainment at High-
Containment Laboratories:
Appendix VII: Comments from the Department of Health and Human
Services:
Appendix VIII: Comments from the Department of Agriculture:
Appendix IX: GAO Contact and Staff Acknowledgments:
Related GAO Products:
Tables:
Table 1: Recommended Biosafety Levels for Laboratories Working with
Human Pathogens:
Table 2: Recommended Biosafety Levels for Activities in Which
Experimentally or Naturally Infected Vertebrate Animals Are Used:
Table 3: Entities Registered with DSAT That Maintain BSL-4
Laboratories, by Calendar Year and Sector:
Table 4: BSL-3 Laboratories Maintained by Entities Registered with
DSAT, by Calendar Year and Sector:
Table 5: BSL-3 Laboratories Maintained by Entities Registered with
APHIS, by Calendar Year and Sector:
Table 6: BSL-3 Laboratories in the State Public Health System:
Table 7: Individuals with Active Access Approvals from DSAT and APHIS,
by End of Calendar Year and Sector:
Table 8: DSAT Budget and Staff for Select Agent Oversight Program by
Fiscal Year:
Table 9: APHIS's Budget and Staff for Select Agent Oversight Program:
Table 10: Federal Agencies without a Mission to Track and Know the
Number of All BSL-3 and BSL-4 Laboratories within the United States:
Table 11: Agents Requiring BSL-2 Containment, Rarely BSL-3 Containment:
Table 12: Agents Typically Requiring BSL-3 Containment:
Figures:
Figure 1: Entities Registered with DSAT That Maintain BSL-4
Laboratories, by Calendar Year and Sector:
Figure 2: BSL-3 Laboratories Maintained by Entities Registered with
DSAT, by Calendar Year and Sector:
Figure 3: BSL-3 Laboratories Maintained by Entities Registered with
APHIS, by Calendar Year and Sector:
Abbreviations:
ABSL: animal biosafety level:
APHL: Association of Public Health Laboratories:
APHIS: Animal and Plant Health Inspection Service:
BMBL: Biosafety in Microbiological and Biomedical Laboratories:
BSAT: biological select agents and toxins:
BSC: biosafety cabinet:
BSL: biosafety level:
BPRP: Biological Personnel Reliability Program:
CDC: Centers for Disease Control and Prevention:
Defra: Department of Environment, Food, and Rural Affairs:
DHS: Department of Homeland Security:
DOD: Department of Defense:
DOE: Department of Energy:
DOJ: Department of Justice:
DOS: Department of State:
DSAT: Division of Select Agents and Toxins:
FBI: Federal Bureau of Investigation:
FDA: Food and Drug Administration:
GM: genetically modified:
HHS: Department of Health and Human Services:
HSE: Health and Safety Executive:
IBC: institutional biosafety committee:
IES: Investigative and Enforcement Services:
LRN: Laboratory Response Network:
NBL: National Biocontainment Laboratories:
NIAID: National Institute of Allergy and Infectious Diseases:
NIH: National Institutes of Health:
NSABB: National Science Advisory Board for Biosecurity:
OIG: Office of Inspector General:
OSHA: Occupational Safety and Health Administration:
PPE: personal protective equipment:
RBL: regional biocontainment laboratory:
rDNA: recombinant deoxyribonucleic acid:
SAPO: Specified Animal Pathogen Order:
TAMU: Texas A & M University:
USAMRIID: U.S. Army Medical Research Institute for Infectious Diseases:
USDA: Department of Agriculture:
[End of section]
United States Government Accountability Office:
Washington, DC 20548:
September 21, 2009:
Congressional Requesters:
Across the United States, federal and state agencies, industries, and
academic institutions are building biosafety level (BSL)-3 and BSL-4
laboratories--commonly referred to as high-containment laboratories--
to research dangerous pathogens (which might accidentally or
intentionally be released into the environment) and emerging infectious
diseases for which risks may not be clearly understood.[Footnote 1] The
recent increase in the number of high-containment laboratories is
primarily due to the U.S. government's burgeoning biodefense research
programs following the 2001 anthrax attacks --totaling $1 billion
annually for new research.[Footnote 2] According to the National
Institute of Allergy and Infectious Diseases (NIAID), these high-
containment laboratories were needed to support its research agenda for
developing medical countermeasures against biothreats. Scientific
research on these dangerous pathogens and the mechanisms by which they
cause disease underpins the nation's ability to successfully combat
infectious diseases and is essential to the development of new and
improved diagnostics, treatments, and preventive measures for a variety
of infectious diseases.
In 2007, we reported on issues associated with the proliferation of
high-containment laboratories in the United States, including risks
posed by biosafety incidents that have occurred in the past.[Footnote
3] The Federal Bureau of Investigation's (FBI) allegation in August
2008 that a scientist at the U.S. Army Medical Research Institute of
Infectious Diseases (USAMRIID) was the sole perpetrator of the 2001
anthrax attacks raised additional concerns about the possibility of
insider misuse of high-containment laboratory facilities, material, and
technology. The public is concerned about these laboratories because
the deliberate or accidental release of biological agents can have
disastrous consequences by exposing workers and the public to dangerous
pathogens. Highly publicized laboratory errors and controversies about
where high-containment laboratories should be located have raised
questions about whether the governing framework, oversight, and
standards for biosafety and biosecurity measures are adequate.[Footnote
4] In this context, you asked us to address the following questions:
[Footnote 5]
1. To what extent, and in what areas, has the number of high-
containment laboratories increased in the United States?
2. Which federal agency is responsible for tracking the expansion of
high-containment laboratories and determining the associated aggregate
risks?
3. What lessons can be learned from highly publicized incidents at high-
containment laboratories and actions taken by the regulatory agencies?
To answer these questions, we interviewed federal agency officials as
well as experts in microbiology, reviewed literature, conducted site
visits, and surveyed 12 federal agencies to determine if they have a
mission to track high-containment laboratories in the United States. We
also interviewed officials from relevant intelligence agencies to
determine if they have a mission to determine insider risks in high-
containment laboratories. The expert panel (see appendix II) that
reviewed this report comprised scientists with substantive expertise in
microbiological and select agent research and the operation of high-
containment laboratories.
We conducted our work from September 2005 through June 2009 in
accordance with generally accepted government auditing standards. Those
standards require that we plan and perform the audit to obtain
sufficient, appropriate evidence to provide a reasonable basis for our
findings and conclusions based on our audit objectives. We believe that
the evidence obtained provides a reasonable basis for our findings and
conclusions based on our audit objectives. (See appendix I for our
scope and methodology and appendix II for a list of the experts who
reviewed this report.)
Background:
Level of Risk in High-Containment Laboratories:
In the life sciences, biosafety is a combination of the containment
principles, technologies, practices, and procedures that are
implemented to prevent the unintentional exposure to pathogens and
toxins or their accidental release. In most countries, infectious
agents are classified by risk group. Agent risk group classification
emphasizes the potential risk and consequences of (1) exposure and
infection for the laboratory worker or (2) the release of the agent
into the environment with subsequent exposure of the general
population.
Risk group classification considers aspects of a given pathogen, in
particular its infectivity; mode and ease of transmission;
pathogenicity and virulence (including induced morbidity and case-
fatality rate); susceptibility to physical or chemical agents; and the
availability or absence of countermeasures, including vaccines,
therapeutic remedies, and cures. Depending on the risk group
classification, research on infectious agents is to be performed in
facilities offering varying levels of containment, applying different
types of primary containment protection (for example, biological safety
cabinets), and ensuring that appropriate practices and procedures are
in place.
Biosafety Levels for Laboratories Working with Human Pathogens:
In the United States, laboratories working with human pathogens are
classified by the type of agents used; activities being conducted; and
the risks those agents pose to laboratory personnel, the environment,
and the community. The Department of Health and Human Services (HHS)
has developed and provided biosafety guidelines outlined in the manual
titled Biosafety in Microbiological and Biomedical Laboratories
(BMBL).[Footnote 6] This manual provides guidelines for work at four
biosafety levels, with BSL-4 being the highest. The NIH Guidelines for
Research Involving Recombinant DNA Molecules (NIH rDNA Guidelines)
[Footnote 7] similarly describe four levels of biocontainment that
closely parallel those described in the BMBL. The NIH rDNA Guidelines
apply to all research involving recombinant DNA at institutions that
receive any NIH funding for such research.
Biosafety level designations, as defined in the BMBL, refer to levels
of containment rather than categories of facilities. These levels of
containment requirements could change from day to day depending on the
risk of the work being conducted with particular agents. For example,
BSL-2 practices are recommended for diagnostic work with B. anthracis,
but BSL-3 practices are recommended for higher-risk work with B.
anthracis, such as aerosol challenges. Table 1 shows the different
biosafety levels specified in the guidelines for laboratories working
with human pathogens.
Table 1: Recommended Biosafety Levels for Laboratories Working with
Human Pathogens:
Biosafety level: 1;
Agent: Not known to consistently cause diseases in healthy adults;
Practices: Standard microbiological practices;
Primary barriers and safety equipment: None required;
Facilities (secondary barriers): Laboratory bench and sink required.
Biosafety level: 2;
Agent:
* Agents associated with human disease;
* Routes of transmission include percutaneous injury, ingestion, and
mucous membrane exposure;
Practices: BSL-1 practice plus;
* limited access;
* biohazard warning signs;
* "sharps" precaution;
* biosafety manual defining any needed waste decontamination or medical
surveillance policies;
Primary barriers and safety equipment: Primary barriers:
* class I or II biosafety cabinets (BSC) or other physical containment
devices used for all manipulations of agents that cause splashes or
aerosols of infectious materials;
Personal protective equipment (PPE):
* laboratory coats, gloves, and face protection as needed;
Facilities (secondary barriers): BSL-1 plus;
* autoclave[A] available.
Biosafety level: 3;
Agent:
* Indigenous or exotic agents with potential for aerosol transmission;
Practices: BSL-2 practice plus;
* controlled access;
* decontamination of all waste;
* decontamination of laboratory clothing before laundering;
* baseline serum;
Primary barriers and safety equipment: Primary barriers:
* class I or II BSCs or other physical containment devices used for all
open manipulation of agents;
PPE:
* protective laboratory clothing, gloves, and respiratory protection as
needed;
Facilities (secondary barriers): BSL-2 plus;
* physical separation from access corridors;
* self-closing, double-door access;
* exhaust air not recirculated;
* negative airflow into laboratory.
Biosafety level: 4;
Agent:
* Dangerous exotic agents that pose a high risk of life-threatening
disease;
* Aerosol-transmitted laboratory infections have occurred; or related
agents with unknown risk of transmission;
Practices: BSL-3 practices plus;
* clothing change before entering;
* shower on exit;
* all material decontaminated on exit from facility;
Primary barriers and safety equipment: Primary barriers:
* all procedures conducted in class III BSCs or class I or II BSCs in
combination with full-body, air-supplied positive pressure personnel
unit;
Facilities (secondary barriers): BSL-3 plus;
* separate building or isolated zone;
* dedicated supply and exhaust, vacuum, and decontamination systems;
* other requirements outlined in the BMBL text.
Source: BMBL, 5th edition.
[A] An autoclave is a device to sterilize equipment and supplies by
subjecting them to high-pressure steam at 121o C or higher.
[End of table]
The levels refer to a combination of laboratory practices and
procedures, safety equipment, and facilities that are recommended for
laboratories that conduct research on these pathogenic agents and
toxins. These laboratories are to be designed, constructed, and
operated to (1) prevent accidental release of infectious or hazardous
agents within the laboratory and (2) protect laboratory workers and the
environment external to the laboratory, including the community, from
exposure to the agents.
Work in BSL-3 laboratories involves agents that may cause serious and
potentially lethal infection. In some cases, vaccines or effective
treatments are available. Types of agents that are typically handled in
BSL-3 laboratories include B. anthracis (which causes anthrax), West
Nile Virus, Coxiella burnetti (which causes Q fever), Francisella
tularensis (which causes tularemia), and highly pathogenic avian
influenza virus. Work in BSL-4 laboratories involves exotic agents that
pose a high individual risk of life-threatening disease or aerosol
transmission or related agents with unknown risks of transmission.
Agents typically handled in BSL-4 laboratories include the Ebola virus,
Marburg virus, and Variola major virus.[Footnote 8]
Animal Biosafety Level Criteria for Vertebrate Animals:
Just as laboratories working with human pathogens are classified by
BSLs 1-4, laboratories working with naturally infected vertebrate
animals are classified by animal biosafety levels (ABSL) 1-4. The four
ABSLs describe facilities and practices applicable to work with animals
infected with agents assigned to biosafety levels 1-4, respectively.
The recommendations describe four combinations of practices,
procedures, safety equipment, and facilities for experiments with
animals involved in infectious disease research and other studies that
may require containment. Table 2 shows the different ABSLs specified in
the guidelines for laboratories working with vertebrate animals.
Table 2: Recommended Biosafety Levels for Activities in Which
Experimentally or Naturally Infected Vertebrate Animals Are Used:
ABSL: 1;
Agents: Not known to consistently cause diseases in healthy adults;
Practices: Standard animal care and management practices, including
appropriate medical surveillance programs;
Primary barriers and safety equipment: As required for normal care of
each species;
Facilities (secondary barriers): Standard animal facility:
* no recirculation of exhaust air;
* directional air flow recommended;
* hand washing sink is available.
ABSL: 2;
Agents:
* Associated with human disease;
* Hazard: percutaneous exposure, ingestion, or mucous membrane
exposure;
Practices: ABSL-1 practice plus:
* limited access;
* biohazard warning signs;
* "sharps" precautions;
* biosafety manual;
* decontamination of all infectious wastes and animal cages prior to
washing;
Primary barriers and safety equipment: ABSL-1 equipment plus primary
barriers:
* containment equipment appropriate for animal species;
Personal protective equipment (PPE);
* laboratory coats, gloves, face and respiratory protection as needed;
Facilities (secondary barriers): ABSL-1 plus:
* autoclave available;
* hand washing sink available;
* mechanical cage washer recommended.
ABSL: 3;
Agents:
* Indigenous or exotic agents with potential for aerosol transmission;
* Disease may have serious health effects;
Practices: ABSL-2 practice plus:
* controlled access;
* decontamination of clothing before laundering;
* cages decontaminated before bedding removed;
* disinfectant foot bath as needed;
Primary barriers and safety equipment: ABSL-2 equipment plus:
* containment equipment for housing animals and cage dumping
activities;
* class I, II, or III biosafety cabinets (BSC) available for
manipulative procedures (inoculation, necropsy) that may create
infectious aerosols;
PPEs:
* appropriate respiratory protection;
Facilities (secondary barriers): ABSL-2 facility plus:
* physical separation from access corridors;
* self-closing, double-door access;
* sealed penetrations;
* sealed windows;
* autoclave available in facility.
ABSL: 4;
Agents:
* Dangerous/exotic agents that pose high risk of life-threatening
disease;
* Aerosol transmission or related agents with unknown risk of
transmission;
Practices: ABSL-3 practices plus:
* entrance through change room where personal clothing is removed and
laboratory clothing is put on; shower on exiting;
* all wastes are decontaminated before removal from the facility;
Primary barriers and safety equipment: ABSL-3 equipment plus:
* maximum containment equipment (i.e., class III BSC or partial
containment equipment in combination with full body, air-supplied
positive-pressure personnel suit) used for all procedures and
activities;
Facilities (secondary barriers): ABSL-3 facility plus:
* separate building or isolated zone;
* dedicated supply and exhaust, vacuum, and decontamination systems;
* other requirements outlined in the text.
Legend: ABSL = animal biosafety level:
Source: BMBL, 5th edition.
[End of table]
Agricultural Biosafety Levels:
According to the BMBL, risk assessment and management guidelines for
agriculture differ from human public health standards. Risk management
for agricultural research is based on the potential economic impact of
animal and plant morbidity and mortality, and the trade implications of
disease. Worker protection is important, but greater emphasis is placed
on reducing the risk of the agent escaping into the environment.
Biosafety level-3 Agriculture (BSL-3Ag) is unique to agriculture
because of the necessity to protect the environment from a high
consequence pathogen in a situation where studies are conducted
employing large agricultural animals or other similar situations in
which the facility barriers serve as primary, rather than secondary,
containment. BSL-3Ag facilities are specially designed, constructed,
and operated at a unique containment level for research involving
certain biological agents in large animal species. BSL-3Ag facilities
are specifically designed to protect the environment by including
almost all of the features ordinarily used for BSL-4 facilities as
enhancements. All BSL-3Ag containment spaces must be designed,
constructed, and certified as primary containment barriers. The
Department of Agriculture's Animal and Plant Health Inspection Service
(APHIS) may require enhancements beyond BSL-3/ABSL-3 when working in
the laboratory or vivarium with certain veterinary agents of concern.
[Footnote 9]
The NIH rDNA Guidelines provide containment standards for research
involving rDNA and animals that are of sizes or have growth
requirements that preclude the use of laboratory containment.
Containment Levels for Plants:
Currently, the BMBL does not provide any comparable classification
levels for laboratories working with plant pathogens.
Federal Agency Involvement in High-Containment Laboratories and Related
Issues:
Many different federal agencies are involved with BSL-3 and BSL-4
laboratories in the United States in various capacities-they may be
users, owners, regulators, or funding sources.[Footnote 10] Examples
include the following:
* The Centers for Disease Control and Prevention (CDC) has its own high-
containment laboratories. The Division of Select Agents and Toxins
(DSAT), located within the Coordinating Office for Terrorism
Preparedness and Emergency Response at CDC, regulates federal, state,
academic, commercial, and private laboratories throughout the United
States that possess, use, or transfer select agents.[Footnote 11] CDC
also funds some laboratory activities carried out in state public
health laboratories, commonly referred to as the Laboratory Response
Network (LRN).[Footnote 12]
* The Department of Agriculture (USDA) has its own laboratories, and
APHIS regulates laboratories working with select agents and toxins
posing a risk to animal and plant health or animal and plant products.
* The National Institutes of Health (NIH), working through its various
institutes, funds biomedical research, some of which requires high
containment laboratories. NIH has containment and biosafety
requirements that apply to this and other research that it funds when
the research uses recombinant deoxyribonucleic acid (rDNA) molecules.
The NIH rDNA Guidelines provide greenhouse containment standards for
rDNA-containing plants, as well as plant-associated microorganisms and
small animals. NIH has its own high-containment laboratories and has
funded the construction of high-containment laboratories at academic
institutions.
* The Food and Drug Administration (FDA) has its own laboratories and
regulates manufacturing of biological products, some of which require
high-containment laboratories.
* The Department of Commerce regulates the export of agents and
equipment that have both military and civilian uses and that are often
found in high-containment laboratories.
* The Department of Defense (DOD) has its own laboratories and funds
research requiring high-containment laboratories.
* The Department of Labor's Occupational Safety and Health
Administration (OSHA) regulates and inspects private-sector employee
safety and health within high-containment biological laboratories and
regulates federal employee safety and health in these laboratories.
However, OSHA does not have statutory responsibility for the
occupational safety and health of (1) contractor employees performing
work at government-owned, contractor-operated sites owned by the
Department of Energy (DOE) or (2) state and local government employees.
* The Department of State (DOS) regulates the export of agents and
equipment from defense-related high-containment laboratories. DOS also
maintains a listing of some high-containment laboratories as part of
U.S. commitments under the Biological and Toxin Weapons Convention.
* The Department of Justice's (DOJ) Federal Bureau of Investigation
(FBI) utilizes high-containment laboratories when its forensic work
involves dangerous biological agents and conducts security risk
assessments for the DSAT and APHIS select agent programs.
* The Department of Homeland Security (DHS) has its own high-
containment laboratories and funds a variety of research requiring high-
containment laboratories.
* The Department of Energy (DOE) has several BSL-3 laboratories doing
research to develop detection and response systems to improve
preparedness for a biological attack.
* The Department of the Interior has its own BSL-3 laboratories for
work with infectious animal diseases.
* The Department of Veterans Affairs has BSL-3 laboratories for
diagnostic and research purposes.
* The Environmental Protection Agency (EPA) has its own BSL-3
laboratories and also coordinates the use of various academic, state,
and commercial high-containment laboratories nationwide as part of its
emergency response mission (eLRN, environmental laboratory Response
Network).
Laws, Regulations, and Guidance Pertinent to High-Containment
Laboratories:
Currently, no U.S. laws provide for federal government oversight of all
high-containment laboratories. However, laws regulating the use,
possession, and transfer of select agents and toxins impose
requirements on entities with high-containment laboratories that work
with these agents.[Footnote 13] The following is a short summary of
pertinent laws, regulations, and guidance.
Pertinent Laws:
Following the Oklahoma City bombing in 1995, Congress passed the
Antiterrorism and Effective Death Penalty Act of 1996 to deter
terrorism, among other reasons.[Footnote 14] Section 511 of title V of
this act gave authority to the HHS Secretary to regulate the transfer,
between laboratories, of certain biological agents and toxins. It
directed the Secretary to promulgate regulations identifying a list of
biological agents and toxins--called select agents--that have the
potential to pose a severe threat to public health and safety,
providing procedures governing the transfer of those agents, and
establishing safeguards to prevent unauthorized access to those agents
for purposes of terrorism or other criminal activities. In response to
this act, the HHS Secretary established the select agent program within
the CDC.
In reaction to the September 11, 2001, terrorist attacks and the
subsequent anthrax incidents, Congress passed several laws to combat
terrorism (to prevent theft, unauthorized access, or illegal use) and,
in doing so, significantly strengthened the oversight and use of select
agents. The USA PATRIOT Act[Footnote 15] made it a criminal offense for
certain restricted persons--including some foreign aliens, persons with
criminal records, and those with mental defects--to transport or
receive select agents. The act also made it a criminal offense for any
individual to knowingly possess any biological agent, toxin, or
delivery system in type or quantity not justified by a peaceful
purpose. Subsequently, Congress passed the Public Health Security and
Bioterrorism Preparedness and Response Act of 2002 (Bioterrorism
Act),[Footnote 16] which (1) expanded the select agent program to
include not only the regulation of the transfer but also the use and
possession of select agents and (2) increased safeguards and security
requirements.
The Bioterrorism Act expanded the select agent program by:
* granting comparable regulatory authorities to USDA for biological
agents and toxins that present a severe threat to plant or animal
health or plant or animal products;[Footnote 17]
* requiring coordination/concurrence between USDA and HHS on select
agents and toxins regulated by both agencies ("overlap" agents and
toxins);
* requiring the Secretaries of USDA and HHS to establish and maintain a
list of each biological agent and toxin (select agent and toxin) that
has the potential to pose a severe threat to public health and safety,
animal or plant health, or animal or plant products and directing the
Secretaries of HHS and Agriculture to biennially review and republish
the select agent list, making revisions as appropriate to protect the
public;
* requiring the Secretaries by regulation to provide for registration
of facilities for the possession, use, and transfer of select agents
and toxins, not just for those facilities sending or receiving select
agents;
* requiring the Attorney General (delegated to the FBI's Criminal
Justice Information Services Division) to check criminal, immigration,
national security, and other electronic databases with information
submitted in the registration process for all individuals and
nongovernmental entities to determine if the registrant is a restricted
person as defined in the USA PATRIOT Act or has been reasonably
suspected by federal law enforcement or intelligence agencies of
committing a federal crime of terrorism or having known involvement in
an organization that engages in terrorism or is an agent of a foreign
power (this is called a security risk assessment);
* requiring the Secretaries to establish a national database that
includes the names and locations of registered entities; the lists of
agents and toxins such entities possess, use, or transfer; and
information regarding the characterizations of such agents and toxins;
* requiring the Secretaries to promulgate regulations that include
safeguard and security requirements for persons possessing, using, or
transferring a select agent or toxin commensurate with the risk such an
agent or toxin poses to public, animal, and plant health and safety,
including required notification to the Secretaries and law enforcement
agencies of theft, loss, or release of a listed agent or toxin; and:
* establishing civil money penalties for persons violating the
regulations and additional criminal penalties for knowingly possessing
a select agent or toxin without registering it or knowingly
transferring a select agent or toxin to an unregistered person.
(See appendix III for the list of select agents and toxins as of
November 11, 2008.)
Pertinent Regulations and Guidance:
Select Agent Program Regulations:
HHS originally established the select agent program within CDC in
response to the Antiterrorism and Effective Death Penalty Act of 1996.
Before the select agent program was created, CDC regulated only the
importation of etiologic agents. CDC published regulations governing
the select agent program that became effective on April 15, 1997. These
regulations provided additional requirements for facilities
transferring or receiving select agents and specifically (1)
established a list of select agents that have the potential to pose a
severe threat to public health and safety, (2) required registration of
facilities before the domestic transfer of select agents can occur, and
(3) developed procedures to document the transfer of agents.[Footnote
18]
Subsequently, the Bioterrorism Act strengthened HHS's authority to
regulate facilities and individuals that possessed biological agents
and toxins that pose a severe threat to public health and safety, and
the Agricultural Bioterrorism Act granted comparable authority to the
USDA to establish a parallel set of requirements for facilities and
individuals that handle agents and toxins that pose a severe threat to
animal or plant health or animal or plant products. USDA delegated its
authority to the Animal and Plant Health Inspection Service (APHIS).
Both CDC and APHIS issued similar regulations governing the select
agent program; these regulations became effective on April 18,
2005.[Footnote 19] CDC issued regulations for select agents posing a
threat to public health and safety. APHIS issued separate but largely
identical regulations for select agents posing a threat to plants and
animals. CDC and APHIS share oversight/registration responsibilities
for overlap select agents that pose threats to both public health and
animal health and animal products.
In developing a list of select agents and toxins that have the
potential to pose a severe threat to public health and safety, the HHS
Secretary was required by the Bioterrorism Act to consider the criteria
listed below. The Secretary directed the CDC to convene an interagency
working group to determine which biological agents and toxins required
regulation based on the following criteria:
* the effect on human health of exposure to the agent or toxin;
* the degree of contagiousness of the agent or toxin and the methods by
which the agent or toxin is transferred to humans;
* the availability and effectiveness of pharmacotherapies and
immunizations to treat and prevent any illness resulting from infection
by the agent or toxin; and:
* any other criteria, including the needs of children or other
vulnerable populations, that the Secretary considers appropriate.
Similarly, the Agricultural Bioterrorism Act required the USDA
Secretary (delegated to APHIS) to consider the following criteria when
selecting biological agents to be included in the list of select agents
that pose a severe threat to animal or plant health or animal or plant
products:
* the effect of exposure to the agent or toxin on animal or plant
health and on the production and marketability of animal or plant
products;
* the pathogenicity of the agent or the toxicity of the toxin and the
methods by which the agent or toxin is transferred to animals and
plants;
* the availability and effectiveness of pharmacotherapies and
prophylaxis to treat and prevent any illness caused by an agent or
toxin; and:
* any other criteria that the Secretary considers appropriate to
protect animal or plant health, or animal or plant products.
Individuals and entities are required to register with CDC or APHIS
prior to possessing, using, or transferring any select agents or
toxins. Prior to registering, entities must designate a responsible
official who has the authority and responsibility to act on behalf of
the entity. Receiving a certificate of registration from the HHS
Secretary or the Administrator of APHIS is contingent on CDC's or
APHIS's review of the application package (APHIS/CDC Form 1) and the
security risk assessment conducted by the FBI (composed of database
checks and consisting of a report of criminal convictions and
involuntary commitments greater than 30 days only) on the individual or
nongovernmental entity (federal, state, or local govermental entities
are exempt), the responsible official, and any individual who owns or
controls the nongovernmental entity. Registration may also be
contingent upon inspection of the facility. Submission of additional
information--such as a biosecurity, biosafety,[Footnote 20] or incident
response plan--is required prior to receiving a certificate of
registration. Registration is valid for one physical location and for a
maximum of 3 years.
For facilities registered with CDC or APHIS that possess, use, or
transfer select agents, the regulations require the following:
1. All individuals in the facility needing access to select agents and
toxins must be approved by the Administrator of APHIS or the HHS
Secretary following a security risk assessment by the FBI prior to
having access (access approval is valid for 5 years).
2. The facility must develop and implement a written security plan
sufficient to safeguard the select agent or toxin against unauthorized
access, theft, loss, or release.
3. The facility must develop and implement a written biosafety plan
commensurate with the risk of the agent or toxin; the plan must contain
sufficient information on biosafety and containment procedures.
4. The facility must develop and implement a written incident response
plan that fully describes the facility's response procedures for the
theft, loss, or release of a select agent or toxin; inventory
discrepancies; security breaches; severe weather; workplace violence;
bomb threats; suspicious packages; and other possible emergencies at
the facility.
5. The facility must provide training on biosafety and security to
individuals with access to select agents and to individuals not
approved for access who will work in or visit areas where select agents
or toxins are handled and stored.
6. The facility must maintain records relating to the activities
covered by the select agent regulations.
7. The facility must immediately notify CDC or APHIS and appropriate
federal, state, or local law enforcement agencies upon discovering a
theft or loss of a select agent or toxin, and notify CDC or APHIS upon
discovering the release of a select agent or toxin.
As a matter of policy, CDC or APHIS inspects the premises and records
of applicants, including a review of all required plans, before issuing
the initial certificate of registration to ensure that the entity is
compliant with the select agent regulations. Also, CDC and APHIS must
be allowed to inspect, without prior notification, any facility where
select agents or toxins are possessed, used, or transferred. CDC and
APHIS perform site visits in cases where an entity may be adding a
select agent or toxin, new laboratory facility, or new procedure that
requires verification of the entity's biosafety plans and procedures.
Other inspections performed by CDC and APHIS include follow-up
inspections based on observations from audits performed by federal
partners, compliance inspections, and investigations of reported
incidents that may have involved biosafety or security concerns that
could affect public, animal, and plant health and safety. CDC and APHIS
use specific checklists to guide their inspections. CDC and APHIS
developed these checklists from the select agent regulations and the
BMBL, and they are available at [hyperlink,
http://www.selectagents.gov]. The BMBL has become the code of practice
for laboratory principles, practices, and procedures.
If CDC or APHIS discovers possible violations of the select agent
regulations, several types of enforcement actions may occur:
* Administrative actions: CDC and APHIS may deny an application or
suspend or revoke a registered entity's certificate of registration if
the individual or entity, responsible official, or owner of the entity
is reasonably suspected of criminal violations or does not comply with
the select agent regulations or if denial, suspension, or revocation is
necessary to protect public, animal, or plant health and safety. A
suspension can be for all select agent work at a registered entity or
be specific to particular agents.
* Civil Money Penalties or Criminal Enforcement: CDC refers possible
violations of the select agent regulations to the HHS Office of
Inspector General (OIG). The HHS-OIG can levy civil money penalties
(for an individual, up to $250,000 for each violation and, for an
entity, up to $500,000 for each violation) or recommend criminal
enforcement (imprisonment for up to 5 years, a fine, or both). As of
April 29, 2009, CDC's DSAT had referred 48 entities to the HHS-OIG for
violating select agent regulations. HHS-OIG had levied $1,997,000 in
civil money penalties against 13 of these entities. Information
regarding these entities can be found on the following Web sites:
[hyperlink, http://oig.hhs.gov/fraud/enforcement/cmp/agents_toxins.asp]
and [hyperlink,
http://oig.hhs.gov/fraud/enforcement/cmp/agents_toxins_archive.asp].
Also, the agricultural select agent program relies on APHIS' own
investigative unit, USDA Marketing and Regulatory Programs--
Investigative and Enforcement Services (IES), for initial
investigations of potential select agent violations. Like the HHS-OIG,
IES can levy civil money penalties or recommend criminal enforcement.
IES refers potential criminal violations to USDA's OIG. From 2002--when
APHIS first became involved with select agents--until May 7, 2009, the
agricultural select agent program referred 39 entities or unregistered
persons to IES for potential violations of the select agent
regulations. USDA has levied $547,500 in civil money penalties against
nine of these entities or unregistered persons. USDA does not publish
information on select agent investigations or the results of these
investigations.
* Referral to DOJ: DSAT or APHIS can refer possible criminal violations
involving select agents to DOJ for further investigation or
prosecution.
Pertinent Guidelines:
The laws and regulations discussed above provide requirements for
individuals and entities possessing, using, or transferring select
agents and toxins but do not apply universally to high-containment
laboratories. However, guidance for operating high-containment
laboratories that is not legally mandatory is available. Pertinent
guidance includes HHS's BMBL manual and the NIH Guidelines for Research
Involving Recombinant DNA Molecules.
HHS's BMBL Manual: The BMBL, prepared by NIH and CDC, categorizes
laboratories on four biosafety levels (BSL) based on risk criteria,
with BSL-4 laboratories being utilized for the study of agents that
pose the highest threat risk to human health and safety. The BMBL
describes a code of practice for biosafety and biocontainment in
microbiological, biomedical, and clinical laboratories. The BMBL serves
as the primary recognized source of guidance on the safe practices,
safety equipment, and facility containment needed to work with
infectious agents. The first publication was in 1984, and the most
recent (5th edition) was published electronically in 2007. The select
agent regulations reference the BMBL as a document to consider when
entities are developing their written biosafety plans. Even though the
BMBL is issued as a guidance document, DSAT and APHIS have incorporated
certain elements of it into their inspection checklists as a
requirement of the select agent program.
The BMBL states that (1) biosafety procedures must be incorporated into
the laboratory's standard operating procedures or biosafety manual, (2)
personnel must be advised of special hazards and are required to read
and follow instructions on practices and procedures, and (3) personnel
must receive training on the potential hazards associated with the work
and the necessary precautions to prevent exposure. Further, the BMBL
(5th edition) provides guidance on biosecurity, such as methods of
controlling access to areas where agents are used or stored. The BMBL
also states that a plan must be in place for informing police, fire,
and other emergency responders concerning the type of biological
materials in use in the laboratory areas.
NIH Guidelines for Research Involving Recombinant DNA Molecules: Some
of the work in BSL-3 and BSL-4 laboratories in the United States
involves rDNA, and the standards and procedures for research involving
rDNA are set by the NIH Guidelines for Research Involving Recombinant
DNA Molecules (NIH rDNA Guidelines).[Footnote 21] Institutions must
follow these guidelines when they receive NIH funding for work with
rDNA. The guidelines include the requirement to establish an
institutional biosafety committee (IBC), which is responsible for (1)
reviewing rDNA research conducted at or sponsored by the institution
for compliance with the NIH rDNA Guidelines and (2) reviewing
categories of research as delineated in the NIH rDNA Guidelines. IBCs
also periodically review ongoing rDNA research to ensure continued
compliance with the guidelines. While the guidelines are only mandatory
for those institutions receiving NIH funding, they have become
generally accepted standards for safe working practice in this area of
research and are followed voluntarily by many companies and other
institutions not otherwise subject to their requirements.
The Number of BSL-4 and BSL-3 Laboratories and Their Workforce Are
Increasing in Different Sectors throughout the United States:
Since 2001, the number of BSL-4 and BSL-3 laboratories in the United
States has increased, and this expansion has taken place across
federal, state, academic, and private sectors and throughout the United
States. Federal officials and experts believe that while the number of
BSL-4 laboratories in the United States is known, the number of BSL-3
laboratories is unknown. Information about the number, location,
activities, and ownership is available for high-containment
laboratories that are registered with the DSAT or APHIS select agent
programs but not for those outside the program.
A number of issues are associated with determining the overall number
of BSL-3 and BSL-4 laboratories. In our discussions with federal agency
officials and experts and in our review of the literature, we found
that the total number depended upon how the question was phrased. While
data were generally available on the number of facilities or sites that
contained a BSL-3 or BSL-4 laboratory, the precise number of
independent rooms within those facilities qualifying as BSL-3 or BSL-4
laboratories was not generally specified. Some facilities contain more
than one actual laboratory. For example, while CDC has two facilities
with BSL-4 capacity, one of the facilities actually contains two
separate BSL-4 laboratories, while the other has four separate BSL-4
laboratories. These officials and experts also told us that counting
the number of laboratories is problematic because the definition of the
term "laboratory" varies. A more meaningful measure is determining the
net square footage of working BSL-4 space. However, this information is
often not available. In addition, there also are methodological issues
associated with determining whether a laboratory is operational or not.
The expansion of high-containment laboratories in the United States
began in response to the emergency situation resulting from the anthrax
attacks in 2001. Understandably, the expansion initially lacked a
clear, governmentwide coordinated strategy. In that emergency
situation, the expansion was based on the perceptions of individual
agencies about the capacity required for their high-containment
laboratory activities as well as the availability of congressionally
approved funding. Decisions to fund the construction of high-
containment laboratories were made by multiple federal agencies in
multiple budget cycles. Federal and state agencies, academia, and the
private sector considered their individual requirements, but a robust
assessment of national needs was lacking. Since each agency has a
different mission, an assessment of needs, by definition, is at the
discretion of the agency. We have not found any national research
agenda linking all these agencies that would have allowed for such a
national needs assessment. Even now, after more than 7 years, we have
not been able to find any detailed projections based on a
governmentwide strategic evaluation of future capacity requirements in
light of existing capacity; the numbers, location, and mission of the
laboratories needed to effectively counter biothreats; and national
public health goals. Without this information, there is little
assurance of having facilities in the right places with the right
specifications to meet a governmentwide strategy.
The Number of BSL-4 Laboratories Is Increasing in Some Sectors:
For most of the past 50 years, there were only two entities[Footnote
22] with BSL-4 laboratories in the United States: federal laboratories
at USAMRIID at Fort Detrick, Maryland, and at the CDC in Atlanta,
Georgia. Between 1990 and 2000, three new BSL-4 laboratories were
built: (1) the first BSL-4 university laboratory (a glovebox, rather
than a conventional laboratory)[Footnote 23] at Georgia State
University in Atlanta; (2) the University of Texas Medical Branch
(UTMB) Robert E. Shope BSL-4 laboratory in Galveston, Texas; and (3)
the Southwest Foundation for Biomedical Research, a privately funded
laboratory in San Antonio, Texas. These entities were registered with
CDC prior to 2004. In 2004, these entities registered their facilities
with DSAT under the select agent regulations.[Footnote 24] As of June
2009, two new BSL-4 laboratories became operational: CDC Emerging
Infectious Diseases laboratory in Atlanta, Georgia, and NIAID Rocky
Mountain laboratory in Hamilton, Montana. To date, there are seven
operational BSL-4 laboratories in the United States.
Table 3 shows the number of entities with BSL-4 laboratories by
calendar year and sector.
Table 3: Entities Registered with DSAT That Maintain BSL-4
Laboratories, by Calendar Year and Sector:
Year: 2004;
Total number of entities: 5;
Number of BSL-4 laboratories by sector:
Federal government: 2;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Year: 2005;
Total number of entities: 5;
Number of BSL-4 laboratories by sector:
Federal government: 2;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Year: 2006;
Total number of entities: 5;
Number of BSL-4 laboratories by sector:
Federal government: 2;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Year: 2007;
Total number of entities: 5;
Number of BSL-4 laboratories by sector:
Federal government: 2;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Year: 2008;
Total number of entities: 5;
Number of BSL-4 laboratories by sector:
Federal government: 2;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Year: 2009;
Total number of entities: 7;
Number of BSL-4 laboratories by sector:
Federal government: 4;
State/local government: 0;
Academic: 2;
Private (nonprofit): 1;
Commercial (for profit): 0.
Source: CDC select agent program as of June 2009.
Note: All six entities in the United States with operational BSL-4
laboratories are registered with DSAT; none are registered with APHIS.
One entity has two BSL-4 laboratories.
[End of table]
Since the anthrax attacks in 2001, seven new BSL-4 facilities are in
the planning, construction, or commissioning stage. Four of these
facilities are in the federal sector, two are in the academic sector,
and one is in the state/local government sector.
The following are the BSL-4 facilities in the planning, construction,
or commissioning stage in the federal sector:
(1) NIAID Integrated Research Facility, Fort Detrick, Maryland;
(2) DHS National Biodefense Analysis and Countermeasure Center, Fort
Detrick, Maryland;
(3) DHS National Bio-and Agro-Defense Facility (NBAF), Manhattan,
Kansas; and:
(4) DOD USAMRIID Recapitalization, Fort Detrick, Maryland. This new BSL-
4 laboratory will replace the existing USAMRIID laboratory.
The following BSL-4 facilities are in the planning or construction
stage in the academic sector and are funded by NIAID:
(5) National Biocontainment Laboratory (NBL) at Boston University,
Boston, Massachusetts, and:
(6) NBL at the University of Texas Medical Branch, Galveston, Texas.
One BSL-4 facility is being built in the state/local government sector
to identify and characterize highly infectious emerging diseases that
pose a threat to public health:
(7) Virginia Division of Consolidated Laboratory Services, Richmond,
Virginia.[Footnote 25]
The total number of BSL-4 laboratories will increase from 7 to 13 when
these laboratories become operational.[Footnote 26] The locations of
the BSL-4 laboratories that are currently registered, under
construction, or in the planning stage are shown in figure 1.
Figure 1: Entities Registered with DSAT That Maintain BSL-4
Laboratories, by Calendar Year and Sector:
[Refer to PDF for image: illustration]
Map of the U.S. indicating the location of the following entities:
NIAID Rocky Mountain Lab, Hamilton, MT (Operational);
NIAID Integrated Research Facility, Fort Detrick, MD (Not operational);
DHS National Biodefense Analysis and Countermeasures Center Fort
Detrick, MD (Not operational);
DOD USAMRIID, Fort Detrick, MD (Operational) (Not operational) (two
labs);
Virginia Division of Consolidated Laboratory Services, Richmond, VA
(Not operational);
DHS National Bio and Agro-Defense Facility (NBAF), Manhattan, KS (Not
operational);
Boston University NBL, Boston, MA (Not operational);
Georgia State University; Atlanta, GA (Operational);
CDC, Atlanta, GA (Operational) (Operational) (two labs);
University of Texas Medical Branch, Galveston, TX (Operational) (Not
operational)(two labs);
Southwest Foundation for Biomedical Research, San Antonio, TX
(Operational).
Source: GAO design based on NIAID information. Art Explosion (map),
open sources.
Note: The figure show 14 laboratories rather than 13 because the
USAMRIID Recapitalization Laboratory at Ft. Detrick is shown along with
the currently operational laboratory that it will eventually replace.
[End of figure]
CDC officials told us that the enormous cost of construction would
preclude operators from building a BSL-4 laboratory unless they were
going to work with one or more of the select agents that require BSL-4
level containment. Based on this reasoning, these officials believe
that they know all existing operational BSL-4 laboratories in the
United States because these laboratories are required to be registered
under the select agent regulations. However, registration with DSAT is
a requirement based on possession of select agents and not ownership of
a BSL-4 laboratory. Therefore, if a BSL-4 laboratory, like the
laboratory in Richmond, Virginia, is commissioned using simulants, and
all diagnostic work is done effectively by using biochemical reagents,
gene probes, and possibly inactivated agents as controls, there would
be no legal requirement for registration. Thus, CDC may not know of all
BSL-4 laboratories.
BSL-3 Laboratories Are Being Built in All Sectors throughout the United
States:
CDC officials stated that unlike the case with BSL-4 laboratories,
operators might build BSL-3 laboratories and not work with select
agents. For example, when building new laboratories or upgrading
existing ones, many laboratory owners may build to meet BSL-3 level
containment, often in anticipation of future work, even though they
intend for some time to operate at the BSL-2 level with BSL-2
recommended agents. Consequently, CDC officials acknowledged that they
do not know the total number of BSL-3 laboratories in the United States
that are not registered to possess, use, or transfer select agents.
In April 2007, we conducted a Web-based survey--based on a search of
publicly available sources--of contacts knowledgeable about high-
containment laboratories (for example, biosafety officers).[Footnote
27] A number of respondents who stated that their institutions had high-
containment laboratories said that their laboratories were not working
with select agents and were therefore not registered with the DSAT or
APHIS select agent program. Although the respondents were not randomly
selected, the results suggest that there may be many BSL-3 laboratories
that do not work with select agents. These laboratories could
potentially be tapped for use if national strategy required additional
capacity.
In 2004, there were far more entities registered with CDC that
maintained BSL-3 laboratories than BSL-4 laboratories (150 versus 5),
and this number grew to 242 in 2008. As shown in figure 2, these
entities accounted for a total of 415 registered BSL-3 laboratories in
2004; this number grew to 1,362 by 2008 (a more than three-fold
increase).[Footnote 28]
Figure 2: BSL-3 Laboratories Maintained by Entities Registered with
DSAT, by Calendar Year and Sector:
[Refer to PDF for image: multiple lime graph]
Year: 2004;
Entities: 150;
Laboratories: 415.
Year: 2005;
Entities: 210;
Laboratories: 782.
Year: 2006;
Entities: 237;
Laboratories: 1086.
Year: 2007;
Entities: 238;
Laboratories: 1176.
Year: 2008;
Entities: 242;
Laboratories: 1362.
Source: GAO analysis based on NIAID information.
[End of figure]
Between 2004 and 2008, the largest increase occurred in the academic
sector (from 120 to 474, an increase of 354 laboratories) followed by
the federal government (from 130 to 395, an increase of 265
laboratories). Table 4 details these increases.
Table 4: BSL-3 Laboratories Maintained by Entities Registered with
DSAT, by Calendar Year and Sector:
Year: 2004;
Number of entities: 150;
Number of laboratories: 415;
Sector:
Federal government: 130;
State/local government: 118;
Academic: 120;
Private (nonprofit): 28;
Commercial (for profit): 19.
Year: 2005;
Number of entities: 210;
Number of laboratories: 782;
Sector:
Federal government: 192;
State/local government: 171;
Academic: 299;
Private (nonprofit): 76;
Commercial (for profit): 44.
Year: 2006;
Number of entities: 237;
Number of laboratories: 1,086;
Sector:
Federal government: 271;
State/local government: 220;
Academic: 438;
Private (nonprofit): 95;
Commercial (for profit): 62.
Year: 2007;
Number of entities: 238;
Number of laboratories: 1,176;
Sector:
Federal government: 347;
State/local government: 254;
Academic: 388;
Private (nonprofit): 119;
Commercial (for profit): 68.
Year: 2008;
Number of entities: 242;
Number of laboratories: 1,362;
Sector: Federal government: 395;
State/local government: 295;
Academic: 474;
Private (nonprofit): 125;
Commercial (for profit): 73.
Source: DSAT program as of February 2009.
Note: Laboratories may be defined by the entity as one room or a series
of rooms (e.g., a suite).
[End of table]
APHIS experienced only a slight increase in the entities with BSL-3
laboratories that registered between 2004 and 2007 (from 41 to 45);
however, in 2008, APHIS transferred 8 BSL-3 facilities to DSAT as the
result of a change in the select agent list rules. Overall, the number
of entities registered with APHIS was much lower than DSAT's total.
(See table 5.)
Table 5: BSL-3 Laboratories Maintained by Entities Registered with
APHIS, by Calendar Year and Sector:
Year: 2004;
Number of entities: 41;
Number of laboratories: 290;
Sector:
Federal government: 179;
State/local government: 10;
Academic: 42;
Private (nonprofit): 20;
Commercial (for profit): 39.
Year: 2005;
Number of entities: 42;
Number of laboratories: 293;
Sector:
Federal government: 179;
State/local government: 10;
Academic: 48;
Private (nonprofit): 20;
Commercial (for profit): 36.
Year: 2006;
Number of entities: 44;
Number of laboratories: 299;
Sector:
Federal government: 179;
State/local government: 15;
Academic: 49;
Private (nonprofit): 20;
Commercial (for profit): 36.
Year: 2007;
Number of entities: 45;
Number of laboratories: 303;
Sector:
Federal government: 179;
State/local government: 15;
Academic: 48;
Private (nonprofit): 20;
Commercial (for profit): 41.
Year: 2008;
Number of entities: 37[A];
Number of laboratories: 281;
Sector:
Federal government: 179;
State/local government: 8;
Academic: 45;
Private (nonprofit): 20;
Commercial (for profit): 26.
Source: APHIS, June 2009.
Note: The number of laboratories includes BSL-3 and ABSL-3
laboratories.
[A] Eight APHIS BSL-3 entities were transferred to CDC as a result of
the select agent list rule change in 2008.
[End of table]
As shown in table 6, the size of the state public health laboratories
network increased following the 2001 anthrax attacks. According to a
survey conducted by the Association of Public Health laboratories
(APHL) in August 2004, state public health laboratories have used
public health preparedness funding since 2001 to build, expand, and
enhance BSL-3 laboratories.[Footnote 29] In 1998, APHL found that 12 of
38 responding states reported having a state public health laboratory
at the BSL-3 level. As of March 2009, all 50 states had at least one
state public health BSL-3 laboratory.[Footnote 30]
Table 6: BSL-3 Laboratories in the State Public Health System:
Calendar year: 2001;
State public health BSL-3 laboratories: 69.
Calendar year: 2002;
State public health BSL-3 laboratories: 71.
Calendar year: 2003;
State public health BSL-3 laboratories: 139.
Source: Association of Public Health laboratories, 2005.
[End of table]
Since the anthrax attacks of 2001, BSL-3 laboratories have started to
expand geographically as well as by sector. As mentioned above, because
individual states need to respond to bioterrorist threats, all 50
states now have some BSL-3 level capacity--at least for diagnostic and
analytical services--to support emergency response.[Footnote 31]
Additionally, NIAID recently funded the construction of 13 BSL-3
Regional Biocontainment Laboratories (RBL) within the academic research
community at the following universities:
(1) Colorado State University, Fort Collins, Colorado;
(2) Duke University Medical Center, Durham, North Carolina;
(3) George Mason University, Fairfax, Virginia;
(4) University of Hawaii, Manoa, Hawaii;
(5) University of Louisville, Louisville, Kentucky;
(6) University of Medicine and Dentistry of New Jersey; Newark, New
Jersey;
(7) Tufts University, Grafton, Massachusetts;
(8) Tulane National Primate Research Center, Covington, Louisiana;
(9) University of Alabama, Birmingham, Alabama;
(10) University of Chicago, Argonne, Illinois;
(11) University of Missouri, Columbia, Missouri;
(12) University of Pittsburgh, Pittsburgh, Pennsylvania; and:
(13) University of Tennessee Health Science Center, Memphis, Tennessee.
NIAID is constructing RBLs to provide regional BSL-3 laboratory
capacity to support NIAID's Regional Centers of Excellence for
Biodefense and Emerging Infectious Diseases Research. The RBLs are
distributed regionally around the country.
Figure 3 shows the sites of NIAID-funded RBLs in the United States.
Figure 3: BSL-3 Laboratories Maintained by Entities Registered with
APHIS, by Calendar Year and Sector:
[Refer to PDF for image: illustration]
Map of the U.S. depicting the location of the following entities:
Tufts University School of Veterinary Medicine, Grafton, MA (Not
operational);
University of Medicine and Dentistry of New Jersey, Newark, NJ
(Operational);
University of Pittsburgh, Pittsburgh, PA (Operational);
Duke University Medical Center, Durham, NC (Operational);
University of Alabama-Birmingham School of Medicine, Birmingham, AL
(Operational);
University Chicago, Argonne, IL (Operational);
George Mason University, Fairfax, VA (Not operational);
University of Tennessee, Memphis, Tennessee (Not operational);
Tulane National Primate Research Center, Covington, LA (Not
operational);
University of Missouri, Columbia College of Veterinary Medicine,
Columbia, MO (Not operational);
University of Louisville, Louisville, KY (Not operational);
Colorado State University, Fort Collins, CO (Operational);
University of Hawaii at Manoa, Honolulu, HI (Not operational).
Source: GAO design based on NIAID information. Art Explosion (map).
[End of figure]
The Workforce in BSL-3 and BSL-4 Laboratories Is Increasing:
As expected, with an increase in the number of entities and
laboratories that work with select agents, the number of individuals
DSAT approved for access to work in the laboratories increased between
2004 and 2008. Table 7 shows the total number of individuals with
active access approvals from DSAT and APHIS.
Table 7: Individuals with Active Access Approvals from DSAT and APHIS,
by End of Calendar Year and Sector:
Year: 2004;
Number of individuals[A]: 8,335;
Sector:
Federal government: 2,629;
State/local government: 1,986;
Academic: 2,309;
Private (nonprofit): 784;
Commercial: (for-profit): 627.
Year: 2005;
Number of individuals[A]: 9,603;
Sector:
Federal government: 2,776;
State/local government: 2,280;
Academic: 2,760;
Private (nonprofit): 982;
Commercial: (for-profit): 805.
Year: 2006;
Number of individuals[A]: 10,134;
Sector:
Federal government: 2,912;
State/local government: 2,420;
Academic: 3,006;
Private (nonprofit): 975;
Commercial: (for-profit): 821.
Year: 2007;
Number of individuals[A]: 10,473;
Sector:
Federal government: 3,067;
State/local government: 2,517;
Academic: 3,090;
Private (nonprofit): 1,004;
Commercial: (for-profit): 795.
Year: 2008;
Number of individuals[A]: 10,365;
Sector:
Federal government: 3,006;
State/local government: 2,384;
Academic: 3,110;
Private (nonprofit): 1,036;
Commercial: (for-profit): 829.
Source: DSAT, as of February 2009.
Note: Data from DSAT and APHIS are available only from 2004 to the
present as entities were not required to be fully registered until
November 12, 2003.
[A] Totals include laboratory staff and laboratory support staff (e.g.,
maintenance, security, and IT support) with access approvals from DSAT
for BSL-2, BSL-3, and BSL-4 laboratories and not the total number of
staff that work with select agents.
[End of table]
In 2004, 8,335 individuals had access approvals. This number increased
to 10,365 by 2008.[Footnote 32] The largest growth was in the academic
sector. In 2004, 2,309 individuals in the academic sector had access
approvals; this number increased to 3,110 by 2008 (an increase of 801
workers). In addition to those workers approved by DSAT, 4,149
individuals had access approvals through APHIS as of February 2009. It
is important to note that as the number of new entities and high-
containment laboratories increases, many new workers are being hired to
work in these laboratories. However, not much is currently known about
the characteristics of this workforce because there are no requirements
in the select agent regulations to report on qualifications. In
addition, there are no national standards for training of workers or
standardized certification programs to test the proficiency of these
workers.
Budget and Resources for Select Agent Oversight Program:
The increase in the number of entities and high-containment
laboratories that work with select agents has implications for federal
oversight. As part of regulatory requirements, DSAT and APHIS staff
inspect each entity prior to issuing a certificate of registration to
ensure that the entity is in compliance with the select agent
regulations. In addition, as part of the entity's renewal process,
which occurs every 3 years, DSAT and APHIS inspectors are required to
reinspect the entity. APHIS performs additional annual compliance
inspections between the 3-year renewal cycles even if there is no
change. DSAT performs additional inspections when an entity adds a
select agent or toxin, a new laboratory facility, or a new procedure
that requires verification of the entity's biosafety plans and
procedures.
As mentioned previously, the number of entities and the number of BSL-
3 laboratories working with select agents increased between 2004 and
2008. As a result of this increase, DSAT now has to inspect more
entities.
As shown in table 8, DSAT had a budget of $14 million and had 25 full-
time equivalent inspectors (5 federal and 20 contract) in fiscal year
2004, when the interim regulations first provided for certificates of
registration. However, its budget decreased between 2004 and 2008. In
2004, DSAT was responsible for providing oversight to 150 entities with
415 BSL-3 laboratories. In 2008, DSAT provided oversight to 242
entities with 1,362 BSL-3 laboratories with a decreased budget and only
3 more inspectors (11 federal and 17 contract). No evaluations are
available to determine how this increased mission and decreased budget
affected the quality of oversight.
Table 8: DSAT Budget and Staff for Select Agent Oversight Program by
Fiscal Year:
Fiscal year: 2004;
DSAT budget (current dollars in millions)[A]: $14.2;
Total DSAT staff: Federal staff[B]: 18;
Total DSAT staff: Contract staff[C]: 58;
DSAT inspectors: Federal inspectors: 5;
DSAT inspectors: Contract inspectors: 20.
Fiscal year: 2005;
DSAT budget (current dollars in millions)[A]: $13.5;
Total DSAT staff: Federal staff[B]: 17;
Total DSAT staff: Contract staff[C]: 63;
DSAT inspectors: Federal inspectors: 6;
DSAT inspectors: Contract inspectors: 23.
Fiscal year: 2006;
DSAT budget (current dollars in millions)[A]: $13.0;
Total DSAT staff: Federal staff[B]: 16;
Total DSAT staff: Contract staff[C]: 64;
DSAT inspectors: Federal inspectors: 9;
DSAT inspectors: Contract inspectors: 22.
Fiscal year: 2007;
DSAT budget (current dollars in millions)[A]: $14.3;
Total DSAT staff: Federal staff[B]: 18;
Total DSAT staff: Contract staff[C]: 60;
DSAT inspectors: Federal inspectors: 10;
DSAT inspectors: Contract inspectors: 17.
Fiscal year: 2008;
DSAT budget (current dollars in millions)[A]: $12.1;
Total DSAT staff: Federal staff[B]: 22;
Total DSAT staff: Contract staff[C]: 64;
DSAT inspectors: Federal inspectors: 11;
DSAT inspectors: Contract inspectors: 17.
Source: DSAT, April 2009.
Notes:
(1) DSAT budget and staffing figures include both the select agent
program and the etiological agent import permit program.
(2) As of April, 2009, the estimated fiscal year 2009 budget for DSAT
was $13.6 million. There currently are 23 federal staff (10 inspectors)
and 64 contract staff (20 inspectors) assigned to DSAT.
[A] This represents the total DSAT budget (ceilings).
[B] These figures reflect the actual number of federal employees
working in DSAT at the end of the fiscal year and do not include vacant
positions. However, they do include the number of federal inspectors.
[C] These figures include the number of contract staff (e.g.,
inspectors, data entry personnel, and record managers) assigned to DSAT
at the end of the fiscal year.
[End of table]
Before 2005, when APHIS had no select agent line item, it funded select
agent program activities using a variety of existing funding sources
(e.g., homeland security). As shown in table 9, APHIS received a budget
of $2.5 million in fiscal year 2005. APHIS officials estimate that the
service has devoted about 5 staff years to select agent inspections for
each year since 2006. No evaluations are available to determine whether
APHIS has sufficient resources to carry out its mission.
Table 9: APHIS's Budget and Staff for Select Agent Oversight Program:
Fiscal year: 2004;
APHIS budget (current dollars in millions[A]): [Empty];
APHIS Staff:
Federal staff[B]: [Empty];
Contract staff: 0;
Federal inspectors (staff years)[C]: 3;
Contract inspectors: 0.
Fiscal year: 2005;
APHIS budget (current dollars in millions[A]): $2.5;
APHIS Staff:
Federal staff[B]: 6;
Contract staff: 0;
Federal inspectors (staff years)[C]: 4;
Contract inspectors: 0.
Fiscal year: 2006;
APHIS budget (current dollars in millions[A]): $3.5;
APHIS Staff:
Federal staff[B]: 18;
Contract staff: 0;
Federal inspectors (staff years)[C]: 5;
Contract inspectors: 0.
Fiscal year: 2007;
APHIS budget (current dollars in millions[A]): $3.5;
APHIS Staff:
Federal staff[B]: 18;
Contract staff: 0;
Federal inspectors (staff years)[C]: 5;
Contract inspectors: 0.
Fiscal year: 2008;
APHIS budget (current dollars in millions[A]): $4.2;
APHIS Staff:
Federal staff[B]: 18;
Contract staff: 0;
Federal inspectors (staff years)[C]: 5;
Contract inspectors: 0.
Fiscal year: 2009;
APHIS budget (current dollars in millions[A]): $5.2;
APHIS Staff: Federal staff[B]: 22;
Contract staff: 0;
Federal inspectors (staff years)[C]: 5;
Contract inspectors: 0.
Source: APHIS, May 2009.
[A] These budget numbers represent dollars allocated to APHIS for the
Agricultural Select Agent Program.
[B] The number of federal staff represents not only staff members who
devote 100 percent of their time to the regulatory program but also
part-time commitments of support personnel, including select agent
entity inspectors (see footnote c).
[C] The number of federal inspectors represents the staff years APHIS
devotes to select agent inspections. APHIS inspections of select agent
laboratories are performed by APHIS veterinarians/inspectors stationed
throughout the United States and two select agent staff members
stationed in Riverdale, Maryland. These inspectors also perform other
similar duties--for example, inspections of entities and containment
facilities in support of APHIS's permitting system pursuant to the
Animal Health Protection Act and the Plant Protection Act. For this
reason, the number of staff years APHIS devotes to select agent
inspections is less than the number of trained inspectors. APHIS
estimates that it has devoted about 5 staff years annually to select
agent inspections since 2006.
[End of table]
No Federal Agency Has the Mission to Track the Expansion of All High-
Containment Laboratories and Regulate Biosafety in the United States:
Currently, no executive or legislative mandate directs any federal
agency to track the expansion of all high-containment laboratories.
Because no federal agency has the mission to track the expansion of BSL-
3 and BSL-4 laboratories in the United States, no federal agency knows
how many such laboratories exist in the United States. While there is a
consensus among federal agency officials and experts that some degree
of risk is always associated with high-containment laboratories, no one
agency is responsible for determining, or able to determine, the
aggregate or cumulative risks associated with the expansion of these
high-containment laboratories.[Footnote 33]
As shown in table 10, none of the 12 federal agencies that responded to
our survey indicated that they have the mission to track and know the
number of all BSL-3 and BSL-4 laboratories within the United States.
Table 10: Federal Agencies without a Mission to Track and Know the
Number of All BSL-3 and BSL-4 Laboratories within the United States:
Agency: Department of Commerce;
Mission to track: No;
Know the number: No.
Agency: Department of Defense;
Mission to track: No;
Know the number: No.
Agency: Department of Energy;
Mission to track: No;
Know the number: No.
Agency: Department of Health and Human Services;
Mission to track: No;
Know the number: No.
Agency: Department of Homeland Security;
Mission to track: No;
Know the number: No.
Agency: Department of Interior;
Mission to track: No;
Know the number: No.
Agency: Department of Justice;
Mission to track: No;
Know the number: No.
Agency: Department of Labor;
Mission to track: No;
Know the number: No.
Agency: Department of State;
Mission to track: No;
Know the number: No.
Agency: Department of Veterans Affairs;
Mission to track: No;
Know the number: No.
Agency: Environmental Protection Agency;
Mission to track: No;
Know the number: No.
Agency: U.S. Department of Agriculture;
Mission to track: No;
Know the number: No.
Source: GAO Survey of Federal Agencies Involved with BSL-3 and BSL-4
laboratories, 2007.
[End of table]
While some federal agencies do have a mission to track a subset of
BSL-3 and -4 laboratories that work with select agents and know the
number of those laboratories, no single regulatory agency has specific
responsibility for biosafety in all high-containment laboratories in
the United States. According to some experts and federal agency
officials, the oversight of these laboratories is fragmented and relies
on self-policing. For example, if an entity is registered under the
select agent regulations, DSAT or APHIS provides oversight. On the
other hand, if an entity receives federal funding from NIH for rDNA
research, the NIH Office of Biotechnology Activities provides
oversight. These agencies assume that all risks would be dealt with by
the entities' self-regulation, consistent with the laboratory practice
guidelines developed by NIH and CDC.[Footnote 34]
Risks Associated with the Expansion of High-Containment Laboratories:
Several federal agencies told us that they should know the number and
location of all BSL-3 and -4 laboratories to carry out their agency
missions. Some intelligence agencies, for example, indicated that--if
there is another incident similar to the 2001 anthrax attacks--they
would need to know the number and location of high-containment
laboratories that do not work with select agents within the United
States to identify all potential sources that could have been used to
prepare the material. These officials told us that a determined
scientist could easily take a small quantity of a select agent from his
or her laboratory to a non-select-agent laboratory to grow the
material.
According to these intelligence agencies, these high-containment
laboratories represent a capability that can be targeted by terrorists
or misused by insiders with malicious intent.[Footnote 35] While some
agencies have the specific responsibility for determining threats from
rogue nations and foreign and domestic terrorists, we found that no
agency has the mission to proactively determine the threat from
insiders.
According to most experts, there is a baseline risk associated with any
high-containment laboratory. With expansion, the aggregate risks
increase. However, no agency has the mission to determine whether the
risks associated with expansion increase in proportion to the number of
laboratories or at some different rate or whether factors such as
location and resource limitations may affect the risk ratio. Because
CDC and USDA regulations require that entities registering with the
select agent program assess only the risks associated with their
individual laboratories, CDC and USDA do not have the mission to
determine the aggregate risks associated with the expansion of high-
containment laboratories that work with select agents.
High-containment laboratories can pose health risks for individual
laboratory workers as well as the surrounding community. However, the
relative risk profile of new versus more established laboratories is
not known. According to CDC officials, the risks from accidental
exposure or release can never be completely eliminated, and even
laboratories within sophisticated biological research programs--
including those most extensively regulated--have had and will continue
to have safety failures.
In addition, while some of the most dangerous agents are regulated
under the CDC-APHIS select agent program, high-containment laboratories
also work with agents not covered under this program. Laboratories
outside the select agent program, especially those working with
emerging infectious diseases, can also pose biosafety risks from
accidental exposure or release. Several of these biological agents are
listed in the BMBL as requiring BSL-3 practices, including West Nile
Virus and Hantavirus. (See appendix IV for a list of biological agents
recommended to be handled in BSL-3 laboratories that are not select
agents).
Consequently, laboratories having capabilities to work with biological
agents, even though they do not posses select agents, are not currently
subject to oversight. These laboratories also have associated
biosecurity risks because of their potential as targets for terrorism
or theft by either internal or external perpetrators. laboratories
outside the select agent program also represent a capability that can
be paired with dangerous pathogens and skilled but ill-intentioned
scientists to become a threat.
Unlike the United Kingdom, the United States Has No Laws to Assist in
Tracking High-Containment Laboratories:
Currently, no laws in the United States specifically focus on all high-
containment laboratories. In the United Kingdom (U.K.), by contrast,
new high-containment laboratories that work with human, animal, or
genetically modified (GM) pathogens need to notify the U.K. regulator
(the Health and Safety Executive (HSE)) and receive either consent (for
GM human pathogens) or license (for animal pathogens) before they
commence their activities.
Prior to construction of the facility, there is no requirement to
inform HSE (except for planning authorities, who look at land use and
building quality); however, in practice, HSE staff are involved at the
design stage and at various points during the construction process.
According to HSE staff, this early involvement has been extremely
helpful in ensuring that new facilities meet the standards set out in
the legislation and supporting guidance (related to the management,
design, and operation of high-containment laboratories).
This involvement has also enabled HSE to address the application of new
technologies in high-containment laboratories (e.g., alkaline
hydrolysis for waste destruction as an alternative to incineration).
While the legislation in the U.K. states that a BSL-4 laboratory must
have an incinerator on site for disposal of animal carcasses, HSE staff
told us that they have been involved in discussions relating to new
facilities where the entities wanted to replace the incinerator with an
alkaline hydrolysis system. Similarly, all BSL-4 laboratories use
cabinet lines (for human pathogens). HSE staff have been in discussion
with entities about proposals to move to a suited system rather than
rely entirely on primary containment. HSE staff told us that they are
recognizing that technologies change and there may be good reasons to
move away from established procedures, assuming that the alternatives
being proposed provide a high degree of assurance that biosafety and
biosecurity will not be compromised by the changes.
In April 2010, the U.K. plans to implement a single regulatory
framework for human, animal, and genetically modified pathogens that
will include a legal requirement for duty holders to consult the
regulatory authority prior to construction and for HSE to be a
statutory consultee as part of the planning authorization.[Footnote 36]
Lessons Learned from Four Incidents Highlight the Risks Inherent in the
Expansion of High-Containment Laboratories:
We reviewed four incidents that highlight the risks inherent in the
expansion of high-containment laboratories: alleged insider misuse of a
select agent and laboratory; Texas A&M University's (TAMU) failure to
report to CDC exposures to select agents in 2006; power outages at
CDC's high-containment laboratories in 2007 and 2008; and the release
of foot-and-mouth disease virus in 2007 at the Pirbright facility in
the U.K.
We reviewed these incidents in detail because they represented
different types of risk associated with high-containment laboratories
and because a significant amount of information was available
concerning them. According to the experts we talked with, many other
incidents and accidents have occurred, mainly as a result of human
error or equipment failure. Fortunately, most incidents/accidents do
not have serious consequences for the health of laboratory workers, the
general population, or the environment. The experts we spoke with also
stated that it is highly probable that many incidents go unreported and
unrecorded because of the lack of such serious consequences. Such
underreporting represents lost opportunities to analyze and learn
lessons that can provide a basis for continuing improvement and
maintenance of laboratory safety.
We are not making any generalizations about the magnitude of the
problem involving other laboratories. However, the lessons we have
identified highlight ways to improve biosafety and biosecurity. These
lessons also have implications for institutional and federal oversight.
Incident 1: Alleged Insider Misuse of a Select Agent and Laboratory:
In September and October 2001, letters containing spores of B.
anthracis powder were distributed through the U.S. postal system to two
senators, Thomas Daschle and Patrick Leahy, and members of the
media.[Footnote 37] The letters led to the first U.S. cases of anthrax
disease related to bioterrorism, and the subsequent investigation by
FBI has been called "Amerithrax."[Footnote 38]
On August 6, 2008, the FBI alleged that the "sole culprit" in the 2001
anthrax attacks was Dr. Bruce Ivins, a U.S. Army scientist with a Ph.D.
in microbiology who had worked for 28 years at the U.S. Army Medical
Research Institute for Infectious Diseases (USAMRIID) at Ft. Detrick,
Maryland.[Footnote 39] USAMRIID is the only DOD laboratory with the
capability to study highly dangerous pathogens requiring maximum
containment at BSL-4. Dr. Ivins had helped develop an anthrax vaccine
for U.S. troops and was in charge of producing large quantities of wet
anthrax spores for research.
Immediately following the anthrax mailings in 2001, FBI took
contaminated evidence to USAMRIID for analysis. Dr. Ivins was tasked by
USAMRIID management to analyze the samples of spores sent through the
mail and was also a technical consultant to the FBI in the early months
of investigation. In March 2003, Dr. Ivins and two of his colleagues at
USAMRIID received the Decoration for Exceptional Civilian Service--the
highest award given to DOD civilian employees--for helping solve
technical problems in the manufacturing of licensed anthrax vaccine.
In December 2001, one of Dr. Ivins' coworkers told Dr. Ivins that she
observed on several occasions unsafe handling procedures by Diagnostic
System Division personnel. She also told him that she might have been
exposed to anthrax spores when handling an anthrax-contaminated letter.
Dr. Ivins began sampling areas in the laboratory space that might have
been contaminated with anthrax. He took samples from the shared office
areas and later decontaminated her desk, computer, keypad, and monitor.
However, he neither documented this incident in the Army record log
book nor notified his superiors. He later acknowledged to Army
officials that this was a violation of protocol. Dr. Ivins' behavior
was detailed in an Army investigation[Footnote 40] conducted in
response to a second round of sampling he conducted in April, but his
name did not surface at that time as a suspect in the anthrax attacks.
After a spill incident inside of suite B-3 in building 1425 in April
2002, Dr. Ivins conducted a second round of unauthorized sampling of
his shared office space and cold side areas outside of suite B-3. These
findings were reported and sparked a buildingwide sampling inspection.
An inspection conducted by the Army 7 months after the anthrax mailing
found that suite B-3 in building 1425 at USAMRIID was contaminated with
anthrax in four rooms of suite B-3 (306, 304, cold room, and 313 (Dr.
Ivins's laboratory)) and that the bacteria had escaped from secure to
unprotected areas in the building. All the areas outside of suite B-3
that tested positive were associated with Dr. Ivins and members of the
Bacteriology Division. The inspection report stated that "safety
procedures at the facility and in individual laboratories were lax and
inadequately documented; that safety supervision sometimes was carried
out by junior personnel with inadequate training; and that exposures of
dangerous bacteria at the laboratory, including anthrax, had not been
adequately reported." (See appendix V for additional information on the
U.S. Army's requirements for high-containment laboratories at the time
of the 2001 anthrax incidents.)
In 2005, the FBI investigation began to shift to a particular
laboratory at USAMRIID, and it began to focus on Dr. Ivins as a suspect
in 2007. According to the FBI, Dr. Ivins had the necessary expertise
and equipment to make the anthrax powder in his laboratory.
Specifically, at the time of the anthrax mailings, Dr. Ivins possessed
extensive knowledge of various anthrax production protocols. He was
adept at manipulating anthrax production and purification variables to
maximize sporulation and improve the quality of anthrax spore
preparations. He also understood anthrax aerosolization dosage rates
and the importance of purity, consistency, and spore particle size due
to his responsibility for providing liquid anthrax spore preparations
for animal aerosol challenges. He also had used lyophilizers,
biological safety cabinets, incubators, and centrifuges in vaccine
research. Such devices are considered essential for the production of
the highly purified, powdered anthrax spores used in the fall 2001
mailings.
According to the FBI's application for a search warrant, at the time of
the attack, Dr. Ivins "(1) was the custodian of a large flask of highly
purified anthrax spores that possess certain genetic mutations
identical to the anthrax used in the attacks; (2) Ivins has been unable
to give investigators an adequate explanation for his late night
laboratory work hours around the time of both anthrax mailings; (3)
Ivins has claimed that he was suffering serious mental health issues in
the months preceding the attacks, and told a coworker that he had
'incredible paranoid, delusional thoughts at times' and feared that he
might not be able to control his behavior; (4) Ivins is believed to
have submitted false samples of anthrax from his laboratory to the FBI
for forensic analysis in order to mislead investigators; (5) at the
time of the attacks, Ivins was under pressure at work to assist a
private company that had lost its FDA approval to produce an anthrax
vaccine the Army needed for U.S. troops, and which Ivins believed was
essential for the anthrax program at USAMRIID; and (6) Ivins sent an e-
mail to a friend a few days before the anthrax attacks warning her that
'Bin Laden terrorists for sure have anthrax and sarin gas' and have
'just decreed death to all Jews and all Americans,' language similar to
the anthrax letters warning 'We Have This Anthrax...Death To America
...Death To Israel.'"[Footnote 41] The FBI stated that in late 2005,
forensic science (genetic analysis) used to trace the anthrax used in
the 2001 attack had genetic markers consistent with the anthrax spores
kept in a flask in the refrigerator in Dr. Ivins's laboratory at Ft.
Detrick, Maryland, to spores in the letters.
During this time, Dr. Ivins kept his security clearance and passed a
polygraph-assisted interrogation (also known as a "lie detector test")
in which he was questioned about his possible participation in the
anthrax attacks. In November 2007, he was denied access to all high-
containment laboratories and, in March 2008, to all laboratories at
USAMRIID. It should be noted that while Dr. Ivins was denied access to
the high-containment suites in November 2007, he was certified at that
time into the personnel reliability program. On July 10, 2008, Dr.
Ivins attended a briefing on a new pneumonic plague vaccine under
development at the Army's laboratory. After this briefing, he was
escorted to a psychiatric evaluation off the installation by local
authorities, and his access rights to the entirety of USAMRIID were
withdrawn by the laboratory commander. An order was subsequently issued
to installation security to prevent Dr. Ivins from entering the
installation unescorted. A written bar order was signed with a plan to
serve the document to Dr. Ivins. Before service of the order occurred,
he died of a drug overdose on July 29, 2008.
Lessons Learned: Insider Risk and Inventory Control of Biological
Agents:
This incident highlights two lessons: (1) an ill-intentioned insider
can pose a risk not only by passing on confidential information but
also by removing dangerous material from a high-containment laboratory,
and (2) it is impossible to have completely effective inventory control
of biological material with currently available technologies. It is
impossible to know the exact number of bacteria or virus in a
laboratory's inventory or working stocks at any specific time. At Ft.
Detrick, ineffective procedures for the control of inventories and the
unlimited use of laboratory facilities allegedly allowed Dr. Ivins the
opportunity to pursue his own ends. As the number of high-containment
laboratories increases, there will be an increase in the pool of
scientists with expertise and, thus, the corresponding risk from
insiders may also increase.
Insiders Can Misuse Material and Facilities:
There are arguably two aspects to insider risk: the motive of the
insider and the ability to misuse material and laboratory facilities.
These two elements need to be understood if effective countermeasures
are to be instituted in a proportionate manner. In this case, assuming
Dr. Ivins was the culprit, no one can conclusively determine what
motivated his actions since he committed suicide before his motive
could be determined.
With regard to the ability to misuse the facility, FBI records show
that Dr. Ivins had unlimited access to material and laboratory
facilities. However, it is still unclear whether the spores in the
letters came directly from the flask under Dr. Ivins's control or
involved some further illicit culturing. In either case, material was
illegally removed and laboratory facilities were misused--at a minimum,
to dry and process the spores. It follows that research laboratories
clearly represent a significant capability that can be potentially
misused, and this capability is growing with the increasing number of
high-containment laboratories. While efforts to strengthen inventory
controls, assess and monitor personnel, and prevent facility misuse
(for example, by video monitoring) have been undertaken to address
insider threats, we are not aware of any evaluation of the
effectiveness of these measures.[Footnote 42] While there are clearly
major difficulties in imposing such controls in research laboratories,
insider risk needs to be recognized and evaluated.[Footnote 43]
Assuming that Dr. Ivins was the perpetrator in the anthrax attacks, he
represents one rogue insider in a period of some 60 years, during which
several thousand scientists and technicians had the opportunity to
commit similar crimes. Thus, the probability of repeating that one
event is, historically, very small. Devising any program to reliably
reduce that figure for biological laboratory personnel is challenging.
Furthermore, some DOD biological laboratory scientists and academicians
we spoke with have pointed out that highly intrusive personnel
reliability programs, which rely on profiling to identify insider
threats, can have a negative effect on staff morale and performance by
institutionalizing the concept that no one can be trusted.[Footnote 44]
The National Science Advisory Board for Biosecurity reported that there
is little evidence that personnel reliability measures are effective or
have predictive value in identifying individuals who may pose an
insider threat.[Footnote 45] In its report, the board recommended that
"it is appropriate to enhance personnel reliability measures for
individuals with access to select agents, but promulgation of a formal,
national personnel reliability program is unnecessary at this time."
On February 11, 2004, DOD issued a directive (5210.88), "Safeguarding
Biological Select Agents and Toxins" (BSAT). This directive established
security policies and assigned responsibilities for safeguarding select
agents and toxins. Specifically, this directive established, among
other things, the following DOD policy:
"Individuals who have a legitimate need to handle or use biological
select agents and toxins, or whose duties afford access to storage and
work areas, storage containers and equipment containing biological
select agents or toxins shall be screened initially for suitability and
reliability. This means that they shall be emotionally and mentally
stable, trustworthy, and adequately trained to perform the assigned
duties and shall be the subject of a current and favorably adjudicated
National Agency Check with Local Agency Checks and Credit Checks for
military and contractor employees and an Access National Agency Check
with credit checks and written inquiries for civilian employees with a
reinvestigation every 5 years and they shall be evaluated on a
continuing basis using the criteria issued by the [Under Secretary of
Defense for Intelligence.]"
On April 18, 2006, DOD issued Instruction 5210.89, "Minimum Security
Standards for Safeguarding Select Agents and Toxins." This instruction
established, among other things, the criteria and requirements for
personnel regarding a biological personnel reliability program (BPRP).
The purpose of a BPRP is to (1) ensure that each individual, who has
authorized access to BSAT and/or supervises personnel with access to
biological restricted areas and BSAT, including responsible and
certifying officials, meets the highest standards of integrity, trust,
and personal reliability and (2) identify any potential risk to public
health, safety, and national security.
Following the announcement of the FBI anthrax investigation at
USAMRIID, the Secretary of the Army organized a task force on August 7,
2008, to evaluate the U.S. Army biological surety program, including
safety, security, and personnel reliability. In response, the Inter-
Service Council for Biosecurity and Biosafety, General Officer Steering
Committee, issued a report on December 12, 2008. This report focused on
seven areas: transportation of select agents and toxins; biological
safety; biological security/physical security; inspection; personnel
reliability program/foreign personnel; inventory/accountability of
select agents and toxins; and training of personnel. Review of all
seven areas indicated that armed service policies, regulations,
standards, and procedures in effect before 2008 met or exceeded all
federal and DOD requirements. The services, however, agreed on the need
to establish common standards in each area. In addition, on March 10,
2008, the Interagency Security Committee Standard defined the criteria
and process to be used in determining the facility security level of a
federal facility as the basis for implementing governmentwide facility
security standards.
In October 2008, the office of the Under Secretary of Defense for
Acquisition, Technology, and Logistics asked the Defense Science Board
Task Force on DOD Biological Safety and Security[Footnote 46] to
address the following questions:
* Are current and proposed policies in DOD and military department
biological safety, security, and biological personnel reliability
programs adequate to safeguard against accidental or intentional loss/
misuse of biological select agents and toxins (BSAT) by external or
internal actors?
* Are current DOD-related laboratories and operations that use or store
BSAT meeting stringent standards for safety, security, and personnel
reliability?
* How do DOD and military department programs compare with other
government agency, academic, and industry programs?
* How can DOD usefully employ experience in other areas requiring the
utmost safety and reliability when handling dangerous material (for
example, the nuclear personnel reliability programs) for biosecurity
policy development and implementation?
In May 2009, the Defense Science Board published its report. With
regard to insider risk, the report concluded that "a determined
adversary cannot be prevented from obtaining very dangerous biological
materials intended for nefarious purposes, if not from DOD
laboratories, then from other sources. The best we can do is to make it
more difficult. We need to recognize this reality and be prepared to
mitigate the effects of a biological attack."[Footnote 47]
In October 2008, the White House Office of Science and Technology
Policy asked the National Science Advisory Board for Biosecurity
(NSABB) to recommend strategies for enhancing personnel reliability
among individuals with access to biological select agents and toxins.
Specifically, the NSABB was asked to identify the optimal framework for
ensuring personnel reliability so that the need for biosecurity was
balanced with rapid progress in the life sciences. The NSABB concluded
in its report that "there is currently insufficient evidence of the
effectiveness of personnel reliability program measures towards
mitigating the risk of an insider threat to warrant the additional
significant burden on research institutions." [Footnote 48] However,
the NSABB did recommend a number of ways to enhance the culture of
research responsibility and accountability at institutions that conduct
select agent research, noting that the recommended actions could be
accomplished without significant expenditures, resources, or
disruptions of research.
On January 9, 2009, an executive order established a governmentwide
working group to strengthen laboratory biosecurity in the United
States.[Footnote 49] The executive order asked the working group to
submit to the President, no later than 180 days after the date of the
order, an unclassified report, with a classified annex as required,
that sets forth the following:
* "a summary of existing laws, regulations, guidance, and practices
with respect to security and personnel assurance reviewed under
subsection (a) of this section and their efficiency and effectiveness;
* recommendations for any new legislation, regulations, guidance, or
practices for security and personnel assurance for all federal and
nonfederal facilities;
* options for establishing oversight mechanisms to ensure a baseline
standard is consistently applied for all physical, facility, and
personnel security and assurance laws, regulations, and guidance at all
federal and nonfederal facilities; and:
* a comparison of the range of existing personnel security and
assurance programs for access to biological select agents and toxins to
personnel security and assurance programs in other fields and
industries."
The working group submitted its draft report and recommendations to the
White House on July 9, 2009. According to HHS, the draft report is to
be formally reviewed and accepted by the co-chairs--the Secretaries of
Defense and Health and Human Services--before it is made public.
While it may be possible to quantify the financial costs required to
initiate and maintain enhanced oversight procedures--such as controls
of inventories and laboratory usage--the impact of such procedures on
work output is unquantifiable but nevertheless very real. According to
some experts and high-containment laboratory scientists, intrusive
personnel reliability programs can also have an adverse impact on staff
work effectiveness.
Accordingly, the security benefits achieved by such procedures must be
evaluated to obtain some understanding of the cost/benefit ratio. Such
an evaluation could incorporate various stress tests and assessments of
procedures against a range of risk scenarios. Effective evaluation
could improve the cost/benefit ratio by concentrating on procedures
with higher returns on investment and could be more acceptable to
laboratory personnel by demonstrating objective benefits. Regular
reevaluation is critical to avoid adding oversight procedures on a
subjective rather than objective basis.
Inventory Procedures Did Not Impede Insider Misuse of Agents:
Prior to the fall of 2001, there were no effective inventory control
procedures at USAMRIID--or indeed other institutions that worked with
select agents--that would have impeded insider misuse of such agents.
Anthrax spores were held in a liquid solution in a flask (RMR-1029)
that originally (October 22, 1997) contained 1000 ml of spore
suspension with a concentration of 3x1010 spores/ml. While the flask
had been under the control of Dr. Ivins since 1997, other laboratory
staff may also have had access to it. However, no one in USAMRIID was
specifically responsible for monitoring the use of materials by
scientists. According to USAMRIID officials, Dr. Ivins's laboratory
notebook contained a record of the amounts of material removed at
various times between 1997 and 2004, when the FBI finally removed the
flask from USAMRIID. Additional undocumented removals from the flask
could have been disguised simply by adding water to restore the volume.
This would have reduced the spore concentration, but this concentration
was apparently never checked. Even if it had been, experts told us that
the normal biological experimental error involved in counting spores
could have disguised the loss of up to 5 percent of the material.
It is unclear whether the anthrax spores put in the letters came
directly from the flask after being dried or whether a very small and
undetectable quantity from the flask was cultured to produce enough new
spores for the letters. In either scenario, the self-replicating nature
of microorganisms and the inherent error associated with determining
the absolute number of microorganisms in solution make inventory
control a formidable if not impossible task with currently available
technologies.[Footnote 50]
Actions Taken by the Regulatory Agency--DSAT--Subsequent to the
Incident:
According to DSAT officials, even though Dr. Ivins' alleged crime
occurred prior to the expansion of the select agent regulations in
2002, DSAT performed an extensive 2-week inspection of the entire
USAMRIID facility in September 2008. DSAT believes that its findings
regarding USAMRIID's inventory records contributed to the decision of
DOD to stand down USAMRIID operations pending a thorough review of its
inventories. In addition, DSAT referred USAMRIID to the HHS-OIG for
further investigation regarding the entity's apparent noncompliance
with the select agent regulations. According to HHS-OIG, this referral
is still an ongoing investigation.
Incident 2: Safety Violations by a University:
In 2006, a series of incidents at the high-containment laboratories at
Texas A&M University (TAMU), and their aftermath, raised issues related
to:
* barriers to reporting laboratory accidents,
* inadequate and ineffective training for laboratory personnel,
* the failure to inform medical personnel about the agents the
laboratory staff work with, and:
* uncertainty about what constitutes a potential exposure.
Barriers to Reporting Laboratory Accidents:
TAMU is registered with DSAT and approved for work on several select
agents. TAMU has several BSL-3 laboratories and works extensively on
animal diseases, including those caused by the select agents Brucella
melitensis, Brucella abortus, and Brucella suis. Brucella can cause
brucellosis in humans, a disease causing flu-like symptoms, such as
fever and fatigue. In severe cases, it can cause infections of the
central nervous system. TAMU is also registered for use of Coxiella
burnetii, an animal agent that can cause Q fever in humans.
In February 2006, a laboratory worker from a non-select-agent
laboratory was helping out with an experiment to aerosolize Brucella.
The laboratory worker had no familiarity with the specifics of working
with Brucella but did have experience working with the aerosol chamber.
It was later determined that the laboratory worker had been exposed to
the agent while cleaning the chamber after the experiment was run.
At the time of the exposure, neither the exposed worker nor anyone else
had any indication that an exposure had taken place. In fact, DSAT
inspectors were on campus days after the Brucella exposure for a
routine inspection but uncovered nothing that alerted them to what had
happened.[Footnote 51] Symptoms did not start to appear in the exposed
worker until more than a month after the exposure, and then the
symptoms were flu-like. Confirmation of brucellosis was not made until
another month had passed and the symptoms had worsened. However, once
the brucellosis was identified, the worker notified appropriate
authorities at TAMU. But no report was subsequently made to DSAT (as
required by federal regulation), and a year passed before--by chance--
an independent watchdog group reviewing unrelated documentation
[Footnote 52] acquired through Texas's freedom of information law,
uncovered the lapse in reporting. This prompted TAMU to notify DSAT.
Training of Laboratory Personnel:
The laboratory worker at TAMU who was exposed to Brucella was not
authorized to work with that agent. The laboratory worker was, we were
told, being allowed in the laboratory only to help out with operating
the aerosolization chamber.[Footnote 53] According to DSAT, TAMU failed
to report to DSAT that it was conducting aerosolization work with
Brucella. Therefore, DSAT had no reason to verify training,
experimental plans, and risk assessments during its inspections.
According to select agent regulations, all staff--not only staff that
have access to select agents or toxins, but also staff that will work
in or visit areas where select agents are handled or stored--are
required to be trained in the specifics of any agent before they work
with it. The training must address the particular needs of the
individual, the work they will do, and the risks posed by the select
agents and toxins. However, the worker at TAMU did not receive training
in the specifics of Brucella, including its characteristics, safe
handling procedures, and potential health effects.[Footnote 54] While
the worker was experienced in general BSL-3 procedures, her normal work
regimen involved working with Mycobacterium tuberculosis, and her
supervisor surmised that the differential in the potential for
infection from Brucella was partially to blame for the
exposure.[Footnote 55] However, experts have told us that if procedures
that are effective to avoid exposure to live, virulent M. tuberculosis
were being followed correctly, these should have been effective for
Brucella despite the differences in the infectious dose (ID50).
[Footnote 56]
The exposed laboratory worker was highly experienced in handling M.
tuberculosis, an infectious agent. The worker had been a laboratory
director of a BSL-2 laboratory for the past 5 years, had a Ph.D. in
microbiology, and was by many accounts highly competent and reliable.
The worker applied the procedures governing safe work with M.
tuberculosis to the Brucella experiment, but her experience with M.
tuberculosis might have provided a false sense of security.
Medical Provider Lacked Information to Diagnose Possible Infection
Quickly:
At the time of the exposure to Brucella at TAMU on February 9, 2006,
the laboratory worker and others in the laboratory did not realize she
had been infected. In fact, DSAT conducted a routine inspection of TAMU
on February 22, 2006--13 days after the exposure--but had no way of
knowing that it had happened. According to the exposed worker, she
first fell ill more than 6 weeks after the exposure. At that time, the
first consultation with her physician indicated that she had the flu.
Institutions generally do not give medical providers information about
the specific agents that laboratory staff work with. Therefore, the
physician was not alerted to the possibility that the worker's symptoms
could be the result of exposure to an infectious agent. After the
symptoms persisted, a consultation with an infectious disease
specialist confirmed that the laboratory worker's blood contained an
unknown microorganism. At that point, the worker recalled her work with
Brucella weeks earlier. The Texas State Public Health Laboratory
confirmed the infection with Brucella on April 16, 2006--62 days after
the exposure. During the interim, the worker had resumed her normal
activities.
By the time the diagnosis was made, the exposed laboratory worker had
become seriously ill. The delay in recognizing the infection resulted
in delay of appropriate treatment, thus aggravating her condition. Such
a misdiagnosis is not uncommon with infectious diseases, as the initial
symptoms often appear flu-like, and brucellosis is not generally
endemic in the population. According to DSAT, the worker might have
developed an even more severe infection, possibly affecting her central
nervous system or the lining of her heart, if the worker had not
recalled the experiment with Brucella and alerted her physician to this
fact. The physician might have been able to correctly diagnose the
infection more quickly if the physician had been informed of the agent
the individual worked with.
In this incident, it was fortunate that transmission of brucellosis
beyond the initial exposed individual was difficult and that there was
no risk of the infection spreading to the surrounding community. Many
other agents--including those that are not select agents (such as SARS
coronavirus and M. tuberculosis)--cause diseases that are transmitted
from human to human through coughing or fluid transfer.[Footnote 57]
Confusion over the Definition of Exposure:
In addition to the incident of exposure to Brucella, DSAT noted that
TAMU failed to report several incidents of potential exposure to
Coxiella burnetii--a select agent and the causative agent for Q fever
in humans. While the Brucella exposure eventually became apparent
because of clinical symptoms in the laboratory worker, the C. burnetii
incidents raised questions about what constitutes sufficient evidence
of an exposure that the entity is required to report to DSAT.
For C. burnetii and other agents, periodically measuring the titer or
antibody levels within the blood serum of laboratory workers working
with those agents provides one indication of exposure. If a person's
titer level is higher than his or her baseline level, then it may be
concluded that the person has been exposed to the agent. In response to
the draft report, HHS stated that the titer should be at least four
times higher than baseline to be considered an exposure. However, HHS
did not provide any support for its assertion, and we could not find
any scientific support for picking this level.
We consider that any titer elevation where that agent is being worked
with in the laboratory requires further detailed investigation. In
addition, the degree of titer elevation that can be considered as
definitively diagnostic needs to be scientifically validated on an
agent-by-agent basis. However, there are issues with using titer levels
as an indication of exposure. For example, determining when the
exposure took place is not straightforward, and methods for determining
titers are not standardized across laboratories.
TAMU has a program to monitor blood serum for those staff working with
C. burnetii. While humans are very susceptible to Q fever, only about
one-half of all people infected with C. burnetii show signs of clinical
illness. During the DSAT inspection that was triggered by the
uncovering of the Brucella incident, DSAT came across clinical records
showing that several laboratory workers had elevated titers for C.
burnetii. No reports of this possible exposure had been sent to DSAT.
DSAT noted this issue and, on April 24, 2007, TAMU submitted the
required Form 3 to DSAT.
However, as a result of subsequent discussion with the individuals who
had the elevated titers, TAMU officials began to doubt whether the
elevated titers resulted from exposures that had occurred at TAMU. In
one case, TAMU said, one of the infected laboratory workers had only
recently been hired by TAMU but had worked in a clinical laboratory in
China where C. burnetii was known to have been present. It is not clear
how the elevated titer related to the employee's baseline titer taken
at the time of employment. In another case, the worker claimed to have
been exposed many years earlier and to have always registered high,
although the actual levels varied. DSAT officials disagreed with this
interpretation and believed the high titers resulted from exposures at
TAMU.
TAMU officials told us that they initially responded to the uncovering
of the elevated titer incidents by reporting to DSAT any subsequent
elevated titer level identified in its laboratory workers. TAMU also
told us that it is now unsure how to proceed; it has notified DSAT
that, in its opinion, an exposure suggested by an elevated titer should
be defined as having occurred only after clinical symptoms appear in
the individual. TAMU has, therefore, ceased reporting incidents where
there are only elevated titers. In the absence of clarity over the
definition of exposure, TAMU officials have chosen to define it as they
see fit.
DSAT officials told us that they disagreed with TAMU's interpretation.
Reporting exposures only after clinical symptoms develop could have
dangerous consequences for laboratory workers and even the public. DSAT
conducted multiple follow-up inspections to assist TAMU in becoming
compliant with the select agent regulations. In addition, on January
18, 2008, DSAT and APHIS posted a guidance document on the analysis of
possible exposure incidents.[Footnote 58] According to DSAT, scenario
20 of this document specifically addresses the recommended response to
an elevated antibody titer in a select agent worker. DSAT officials
noted that reporting exposures only after clinical symptoms develop--
given the requirements of the select agent regulations and the guidance
provided in the theft, loss, and release guidance document--would be
considered a violation of the select agent regulations.
Lessons Learned: Barriers to Reporting, Compliance with Regulations
Regarding Training, Informing Medical Providers, and Defining Exposure:
The common theme in the TAMU incidents was a lack of rigor in applying
fundamental safety and training procedures coupled with a culture that
embodied a reluctance to be open about problems both within the
organization and with the regulator. According to our experts, such
cultural reticence has historically been a factor in many previous
incidents and can be remedied only by appropriate leadership at the
highest level of the organization coupled with robust and continued
action by the regulator.
Barriers to Reporting Need to Be Identified and Overcome:
According to the literature and discussions with federal officials and
experts, accidents in laboratories do occur, mostly as a result of
human error due to carelessness, inadequate training, poor judgment,
fatigue, or a combination thereof.[Footnote 59] In the case of theft,
loss, occupational exposure, or release of a select agent, the
laboratory must immediately report certain information to DSAT or
APHIS.
It has been suggested that there is a disincentive to report laboratory-
acquired infections and other mishaps at research institutions because
it could result in (1) negative publicity for the institution and the
worker or (2) scrutiny from a granting agency that might lead to a
suspension of research or an adverse effect on future funding.[Footnote
60]
In order to enhance compliance with reporting requirements, barriers
need to be identified, and targeted strategies need to be applied to
remove those barriers. The literature identifies a number of barriers,
including:
* the lack of explicit standardized protocols;
* the lack of effective training on protocols;
* the lack of awareness that infection may have been laboratory-
acquired;
* reporting systems that may have required individuals to pass through
layers to reach the biosafety office (e.g., the supervisor, laboratory
manager, or principal investigator);
* fear of punitive measures at the laboratory or institutional level;
* individual or institutional embarrassment;
* a poor relationship with medical support services (such as
occupational safety and health services); and:
* the lack of useful investigation/follow-up/feedback.
In addition, these incidents need to be analyzed so that (1) biosafety
can be enhanced by shared learning from mistakes and (2) the public can
be reassured that accidents are thoroughly examined and the
consequences of an accident are contained. One possible mechanism for
analysis discussed in the literature is the reporting system used for
aviation incidents that is administered by the National Transportation
Safety Board and the Federal Aviation Administration.[Footnote 61] When
mistakes are made, they are analyzed and learned from without being
attributed to any one individual. Although experts have agreed that
some form of personal anonymity would encourage reporting, it is not
clear how this mechanism would be applied to high-containment
laboratories where, for example, one may not know about the exposure or
whether the event is significant enough to be reported.
Compliance with Regulations Regarding Agent-and Experimental Task-
Specific Training Is Needed to Ensure Maximum Protection:
The select agent regulations require safety risk assessments whenever
work with select agents is proposed. Risk assessments are of paramount
importance because the investigator, management, and biosafety
representatives must establish guidelines for safe, secure, and
efficient research. Personnel working with select agents need training
to ensure their own safety and that of coworkers and the surrounding
community. Training is specifically designed to address select agent
characteristics that include infectivity and pathogenicity. Training
must also address hazardous operations such as intentional
aerosolization, centrifugation, and homogenization. Some laboratories
require inexperienced workers to be mentored by personnel experienced
in containment procedures, a process that can take up to a year to
complete. The mentor maintains a checklist of important operations that
must be performed in a responsible manner before the worker will be
allowed to work independently. Non-laboratory personnel who require
access to high-containment laboratories (inspection, maintenance, and
calibration staff) must also receive training that covers emergency
response and agent-specific information.
If TAMU had provided effective, measurable staff training--including
protocol-specific training on agent characteristics for Brucella
(infectivity and pathogenicity), common routes of infection, and
medical signs and symptoms information--the worker might have been more
aware of the dangers involved when cleaning the aerosol chamber and
could have been protected from this exposure. Typical routes of
infection differ for M. tuberculosis and Brucella, and normal
procedures, including gowning and respiratory equipment, vary for the
two agents. For example, the laboratory worker wore protective glasses,
but they were not tight fitting. Experts told us that if procedures
that are effective to avoid exposure to live virulent M. tuberculosis
were being followed correctly, these should have been effective for
Brucella despite the difference in the infectious dose.
According to an expert who has managed high-containment laboratories,
there are risks involved in working alternately in BSL-2 and BSL-3
laboratories with their different levels of procedures and practices.
Laboratory workers may develop a routine with BSL-2 procedures that may
be difficult to consciously break when working with the more dangerous
agents and activities requiring BSL-3 containment. Adequate training
can help to minimize the risks involved.
Standardized Mechanisms for Informing Medical Providers about the
Agents Laboratory Staff Work with Must Be Developed:
Severe consequences for the worker can result from delays in (1)
recognizing when an exposure has occurred or (2) medical providers
accurately diagnosing any resulting infection. Further, if the worker
acquires a disease that is easily spread through contact (direct
physical and/or respiratory), there can also be severe consequences for
the surrounding community.
According to the BMBL, the incidents causing most laboratory-acquired
infections are often accidental and unknown. Those involved can
conclude that an exposure took place only after a worker reports
illness--with symptoms suggestive of a disease caused by the relevant
agent--some time later. An infected person may be contagious for weeks
until clinical symptoms become apparent. It is important that exposure
be identified as soon as possible so that proper diagnosis and prompt
medical treatment can be provided. To do so, medical providers need to
be informed, in a standardized way, of all the agents that laboratory
staff work with.
The issue of recognizing exposure and infection is not new, and
organizations have put in place systems and procedures that, while not
infallible, greatly facilitate such recognition. As part of the
oversight process, a review and evaluation of such procedures and their
effectiveness are likely to be beneficial.
Current Confusion over the Definition of Exposure Needs to Be
Addressed:
According to our experts, a system that requires documentation of all
accidental releases of select agents by whatever means and ensures that
this information is available to the inspecting/oversight authority
would provide both a valuable database and the foundation for any
further investigation. Any accidental release in an area where
unprotected personnel are present should then be considered a de facto
exposure and be immediately reported to the oversight authority whether
or not there is any resulting infection. Laboratory personnel who
contract any infection, even if there is no evidence of exposure,
should inform their physician about their work, including details of
the specific agent(s) that they work with.
When we asked DSAT officials about the confusion over the definition of
an exposure, they agreed that the terms need to be clearly defined and
stated that they were drafting new guidance.[Footnote 62] DSAT
officials noted, however, that it is unwise to wait until clinical
symptoms appear before determining that an exposure has taken place, as
this could potentially endanger a worker's life and, in the case of a
communicable disease, the lives of others. A DOD and NIH expert on this
issue told us that correctly interpreting the meaning of elevated
titers--whose characteristics can vary by agent, host, and testing
laboratory--is challenging since many serological testing methods have
not been validated.
To help clarify any confusion about what is considered a reportable
theft, loss, or release, CDC released a new guidance document.[Footnote
63]
Scenario 20 in this document is an attempt to provide a simple approach
by identifying three possible explanations for an elevated titer.
However, it fails to go far enough and should state that an elevated
titer of an agent that is being worked with in the laboratory should be
regarded as prima facie evidence of exposure unless and until proved
otherwise. Although clinical samples should then be taken at once to
look for evidence of active infection, treatment of the person, as
appropriate, should begin without delay to protect the health of the
individual and, in some cases, safeguard the wider community.
Serological testing is an indirect diagnostic tool suggesting, but not
proving, exposure to an agent and is typically used to direct follow-up
with more conclusive tests. Because elevated titers can be due to
reasons other than active infection with a particular agent, the
results need to be treated with caution. Nevertheless, an elevated
antibody titer in cases where that agent is being worked with in the
laboratory must always be a matter of concern and action.
Serological testing is not definitive and scenario 20 does not provide
clear guidance with regard to follow-up actions. Accordingly, standard
operating procedures need to be developed by the institutions working
together with biosafety officers/responsible officials and occupational
health physicians to describe the appropriate course of action when
elevated titers are observed.
The use of serological testing as a method to identify potential
exposures to select agents must be approached with a high degree of
caution. First, guidelines must be very clear regarding the intended
use of any serology-based screening program. If routine screening
indicates elevated antibody titers against a specific pathogen over
baseline levels, it may suggest a laboratory exposure to a pathogen;
however, alternative explanations are also feasible. The increase in
titers may indicate natural exposure to the agent (depending on the
agent and location of the laboratory). The increase could also result
from inconsistencies associated with laboratory testing. Most
serological assays for select agents are not commonly conducted in
clinical laboratories and are mostly performed in research
laboratories. As such, these assays may not be properly controlled and
validated. Assay-to-assay variation may be high, especially if
experience is limited. Additionally, such assays are not particularly
robust unless baseline specimens are available for comparison testing
and serum samples are collected at relatively short intervals (for
example, 3 to 6 months).
Similarly, a serological screening program used as a method to diagnose
infection or prevent the spread of contagious pathogens to the
community is unlikely to be successful unless samples are taken at
short intervals, as elevated antibody titers are usually detected after
the period of maximum contagiousness of most pathogens. Therefore, the
most appropriate use for a serological screening program would be to
identify past exposures and to facilitate remedial training or conduct
retrospective risk analyses that might lead to improved risk mitigation
procedures and policies that might prevent future exposures. It is
critical that guidance on the use of blood screening programs clearly
identify the purpose of these programs and also provide guidance on how
information from these programs should be used. Any suspicion of
exposure should be reported and investigated, and the result of that
investigation should be reported, thus providing a complete picture for
DSAT and reducing subjective bias in reporting.
The development of scientifically sound and standardized methods of
identifying exposure is critical so that individual laboratory owners
are not left to determine for themselves what is and what is not
reportable. DSAT and APHIS could provide specific guidance on exposure
benchmarks for each of the different select agents and toxins.
Actions Taken by the Regulatory Agency--DSAT--Subsequent to the
Incident:
On April 20, 2007, DSAT issued a cease-and-desist order suspending work
with Brucella species at TAMU. On June 30, 2007, DSAT suspended all
work with select agents at TAMU. The DSAT concerns included whether
TAMU had a plan to prevent unauthorized access to select agents and
toxins and a program that provided effective medical surveillance of
occupational exposures to select agents and toxins. DSAT conducted a
comprehensive site review and released a report in August 2007 that
detailed a long list of safety violations, including instances in which
the school did not immediately report or neglected to report laboratory
worker infections or exposure to Brucella or C. burnetii. It also
extended the suspension of research with select agents until the
university addressed the issues in the August report.
HHS's Office of Inspector General (OIG) imposed a fine on TAMU for the
select agent violations. The HHS OIG was delegated authority to impose
civil monetary penalties of up to $250,000 against an individual and up
to $500,000 against any other person, including any entity.[Footnote
64] The HHS OIG and TAMU disagreed on the number of violations. In
February 2008, TAMU agreed to pay a $1 million fine, which was an
unprecedented amount for a fine paid by any institution under the
select agent program.
Incident 3: Power Failures at CDC's High-Containment Laboratories:
Continuity of electrical power is vital for the safe functioning of
high-containment laboratories, in particular since maintenance of
essential pressure differentials using electrically driven fans
provides an important barrier for preventing the uncontrolled release
of agents.[Footnote 65] Lapses in electrical power that occurred at a
CDC laboratory raise concerns about standards in high-containment
laboratory facility design, management of construction, and operations.
[Footnote 66]
On June 8, 2007, the CDC campus in Atlanta experienced lightning
strikes in and around its new BSL-4 facility, and both the Georgia
Power-supplied primary power and CDC-supplied backup power from its
centrally-located generator plant were unavailable.[Footnote 67] The
high-containment laboratory facility, not operational at the time, was
left with only emergency battery power--which can provides limited
electrical power for functions such as emergency lighting to aid in
evacuation. Among other things, the outage shut down the high-
containment laboratory's negative air pressure system.[Footnote 68]
While investigating the power outage, the CDC later determined that,
some time earlier, a critical grounding cable buried in the ground
outside the building had been cut by construction workers digging at an
adjacent site. The cutting of the grounding cable, which had hitherto
gone unnoticed by CDC facility managers, compromised the electrical
system of the facility that housed the BSL-4 laboratory.[Footnote 69]
With the grounding cable cut, the lightning strikes caused the circuit
breakers in the building's switchgear to disengage or open, resulting
in a loss of primary power to the building. In addition, when the
circuit breakers disengaged, the CDC's backup generators were
electrically isolated from the building and could not supply the
building with power. It took approximately an hour for the CDC facility
staff to reset the circuit breakers in the building to reengage the
primary power.
Because of the June 2007 power outage incident, questions about the
design of the backup power system for the new facility resurfaced. When
the CDC designed the backup power system for the new BSL-4 facility, it
decided to use diesel generators centralized at CDC's utility plant
that also serve other facilities, as well as functions such as
chillers, on the campus. According to internal documents provided to
us, during the design phase for the facility, some CDC engineers had
questioned the choice of this remotely placed, integrated design rather
than a simpler design using local backup generators near the BSL-4
facility.
According to CDC facility officials, the full backup power capabilities
for the new BSL-4 facility were not in place at the time of the power
outage but were awaiting completion of other construction projects on
campus. Once these projects are completed, these officials said, the
new BSL-4 facility will have multiple levels of backup power, including
the ability to get power from a second central utility plant on campus,
if needed. But some CDC engineers that we talked with questioned the
degree of complexity in the design. They worried that an overly
integrated backup power system might be more susceptible to failure. As
a result of the power outage, CDC officials conducted a reliability
assessment for the entire campus power system, which included the
backup power design for the new BSL-4 facility. CDC concluded that its
existing centrally located generators and planned power-related
construction projects with equipment upgrades were more reliable and
cost-effective than scenarios that locate generators at individual
buildings.
CDC officials reported that its backup power system is tested monthly,
as required by building code. In commenting on our draft report, CDC
provided studies and data that showed the theoretical reliability of
the power system. However, CDC could not provide us documentation of
actual non-testing instances where the backup generator system operated
as designed. This incident highlighted the risks inherent in relying on
standard building codes to ensure the safety of high-containment
laboratories--as there are no building codes and testing procedures
specifically for high-containment laboratories.
In a second incident, on Friday January 4, 2008, CDC officials told us
that nearby construction again damaged the grounding system of the
building containing the new BSL-4 facility. The damage was observed
when it occurred, but the cable was not repaired until the following
week. While there was no loss of power to the BSL-4 facility, the
potential for repeating a grounding-related power failure existed until
repairs were made.
According to CDC officials, at the time of both incidents, the new BSL-
4 facility in building 18 was in preparation to become fully
operational. No laboratory work of any kind had been conducted inside
the BSL-4 laboratories, and no live agents were inside the facility as
the commissioning process was still ongoing and the laboratories were
not activated. However, given that the grounding cables were cut, it is
apparent that the building's integrity as it related to adjacent
construction was not adequately supervised. Further, according to CDC
officials, standard procedures under building codes do not require
monitoring of the integrity of the electrical grounding of the new BSL-
4 facility. CDC has now instituted annual testing of the electrical
grounding system as the result of its review of these incidents.
[Footnote 70]
According to CDC officials, a third incident occurred on July 11, 2008,
when a bird flew into the high voltage side of one of the Georgia Power
transformers on the CDC campus, causing a failure in the primary
electrical power supplied to buildings containing BSL-3 facilities. The
CDC's backup generators did not provide power because of the cascading
effects of a failure by one of the generators. As in the June 2007
incident, the facilities were left with only temporary battery power,
shutting down the fans powering the facility's negative air pressure
system. The generator problems were corrected by CDC in approximately
an hour, at about the same time that Georgia Power completed its
repairs and primary electrical power was restored.[Footnote 71]
Lessons Learned: BSL -3 and -4 Laboratory Safety Measures Must Be
Commensurate with the Level of Risk These Laboratories Present:
In any workplace building--regardless of the nature of its activities--
there are safety features to protect the physical safety of workers.
Various building codes cover many aspects of building design and
construction required to achieve this safety objective, but the codes
are subject to local interpretation. In general, the building codes
enable (1) personnel to safely evacuate and (2) rescue personnel or
firefighters to perform their jobs. By definition, additional hazards
beyond those anticipated by standard building codes potentially exist
in high-containment laboratories (BSL-3 and BSL-4), and they are
addressed in BMBL. However, according to CDC and NIH, BMBL is only
advisory.
BMBL contains principles and guidelines, but the document does not
provide specific detail on how functional requirements are to be
translated into design solutions. According to our experts, there have
been instances where modifications to laboratories were required after
construction to achieve the necessary compliance. A more active, early,
and continuing dialogue between builders, operators, and regulators may
be beneficial in avoiding such waste and is especially relevant where
tax dollars are committed to the creation or upgrading of high-
containment laboratories.
Because BMBL addresses issues relating to maintaining the containment
of biological agents to protect both workers and the wider public, its
guidelines are potentially more restrictive than the building codes.
According to our expert panel, a clear and unambiguous set of standards
stating the various capabilities that are required to maintain the
integrity of all high-containment laboratories is necessary. Such a set
of standards will need to integrate building codes with the BMBL
provisions or amendments thereto. These standards should be national--
not subject to local interpretation--and address the possibility that
one or more emergency or backup systems may fail. Most importantly, any
set of scenarios aimed at maintaining containment integrity must be
empirically evaluated to demonstrate its effectiveness. Adequate
oversight of any nearby activities--such as adjacent construction with
its potential to compromise buried utilities--must also be taken into
consideration when evaluating the safety measures required to manage
the risks of high-containment laboratories.
The CDC's BSL-4 laboratory was designed with multiple layers of
electrical power so that if primary power failed, a secondary source of
power would be in place for continuity of operations. Failure to
monitor the system's integrity, however, compromised the ability of
either power source to support critical operations. The power outages
at CDC demonstrate a need to create understanding throughout the
organization that effective biosafety involves layers of containment
and, furthermore, that the loss of any one layer is serious even though
the remaining layers, as intended, do maintain containment. Thus,
procedures are required to regularly assess the functional integrity of
every layer of containment and to initiate immediate corrective actions
as required. The fact that taken as a whole, containment is being
maintained is not a sufficient measure of system integrity: each
component must be individually assessed and its operational
effectiveness validated on a regular schedule.
Actions Taken by the Regulatory Agency--DSAT--Subsequent to the
Incident:
According to DSAT, since the CDC laboratory was not registered under
the select agent regulations at the time of the incident, no DSAT
action was required.[Footnote 72]
Incident 4: Release of Foot-and-Mouth Disease in the United Kingdom:
High-containment laboratories are highly sophisticated facilities that
require specialized expertise to design, construct, operate, and
maintain. Because these facilities are intended to contain dangerous
microorganisms, usually in liquid or aerosol form, even minor
structural defects--such as cracks in the wall, leaky pipes, or
improper sealing around doors--could have severe consequences.
Supporting infrastructure, such as drainage and waste treatment
systems, must also be secure.
In August 2007, foot-and-mouth disease contamination was discovered at
several local farms near Pirbright in the U.K., the site of several
high-containment laboratories that work with live foot-and-mouth
disease virus. Foot-and-mouth disease is one of the most highly
infectious livestock diseases and can have devastating economic
consequences. For example, a 2001 epidemic in the U.K. cost taxpayers
over £3 billion, including some £1.4 billion paid in compensation for
culled animals.[Footnote 73] Therefore, U.K. government officials
worked quickly to contain and investigate this recent incident.
Lesson Learned: Facilities Supporting High-Containment Laboratories
Must Ensure the Operational Effectiveness of Physical Infrastructure:
The investigation of the physical infrastructure at the Pirbright site
found evidence of long-term damage and leakage of the drainage system
servicing the site, including cracked and leaky pipes, displaced
joints, debris buildup, and tree root ingress. While the definitive
cause of the release has not been determined, it is suspected that
contaminated waste water from Pirbright's laboratories leaked into the
surrounding soil from the deteriorated drainage pipes and that live
virus was then carried off-site by vehicles splashed with contaminated
mud.
The cracked and leaky pipes found at Pirbright are indicative of poor
maintenance practice at the site. The investigation found that (1)
monitoring and testing for the preventive maintenance of pipe work for
the drainage system was not a regular practice on-site and (2) a
contributing factor might have been a difference of opinion over
responsibilities for maintenance of a key pipe within the drainage
system.
High-containment laboratories are expensive to build and expensive to
maintain. Adequate funding for each stage needs to be addressed.
Typically, in large-scale construction projects, funding for initial
construction comes from one source, but funding for ongoing operations
and maintenance comes from another. For example, NIAID recently funded
13 BSL-3 laboratories as regional biocontainment laboratories (RBL) and
2 BSL-4 laboratories as national biocontainment laboratories (NBL).
According to NIAID, it contributed to the initial costs for planning,
design, construction, and commissioning and provided funding to support
the operation of these facilities. For these laboratories, the
universities are partially responsible for funding maintenance costs.
[Footnote 74]
The Pirbright incident shows that beyond initial design and
construction, ongoing maintenance plays a critical role in ensuring
that high-containment laboratories operate safely and securely over
time. Because even the smallest of defects can affect safety, ensuring
the continuing structural integrity of high-containment laboratories is
an essential recurring activity.
The failure of part of the physical infrastructure at the U.K.'s
Pirbright facility and the outbreak of foot-and-mouth disease highlight
the importance of ongoing maintenance of such facilities, together with
clear lines of responsibility regarding shared infrastructure
facilities. In addition, this incident and other incidents emphasize
the importance of regulators and laboratories working in partnership to
either ensure that funding to maintain the infrastructure is available
or alter work programs and eliminate activities that cannot be
performed safely.
Actions Taken by the U.K. Regulatory Agency Subsequent to the Incident:
Since the outbreak of foot-and-mouth disease originating from
Pirbright, a number of regulatory decisions have been made:
1. The U.K. government undertook a review of the regulatory framework
governing work with animal pathogens that resulted in a November 2007
report. The government accepted all the report's recommendations, which
included (1) moving regulation of work with animal pathogens from Defra
to HSE and (2) developing a single regulatory framework covering work
with human and animal pathogens based on the model provided by the
Genetically Modified Organisms (Contained Use) Regulations 2000. This
framework adopts a risk-based approach to regulation.
2. The Specified Animal Pathogens Order (SAPO) was amended in April
2008 to give inspectors increased powers, including the power to serve
improvement and prohibition notices on entities (called duty holders in
the U.K.) to remedy poor standards in such areas as containment and
management. At the same time, HSE entered into an agency agreement with
Defra to inspect premises where work with SAPO agents is carried out
before Defra issues licenses; the license conditions are based on
recommendations from HSE. Furthermore, HSE inspectors investigate any
accidents and also proactively inspect facilities to ensure compliance
with the license conditions.
3. Both organizations at Pirbright (Institute for Animal Health (IAH)
and Merial) had their licenses amended or withdrawn following the
outbreak. The IAH license was amended to allow diagnostic work (in the
epidemiology building) and a limited amount of research in the
arbovirology building. No animal work has been licensed to date,
although new animal house facilities are nearing completion, and work
may be licensed later this year.
4. All the drainage systems on-site have been tested and relined, and a
new dual containment system has been laid to connect laboratories to a
refurbished heat treatment plant. This new system is not yet
operational, although it is in the final stages of commissioning. In
the meantime, no laboratory or manufacturing effluent is discharged to
the relined drainage system unless it has been heat treated by
autoclaving (IAH) or been through a validated heat treatment cycle
(Merial). The only effluent going to the drain and to the final
chemical treatment plant is shower water, which should not contain
virus as all activities are carried out in cabinets or in enclosed
systems.
5. A newly refurbished building on the IAH has recently been licensed
to allow small scale research on a number of SAPO 4 viruses.
6. Merial was fully relicensed following amendments to its procedures
and joint Defra and HSE inspections. The new licenses are more detailed
than the original versions and impose many more license conditions on
the company.
7. No enforcement action has been taken against either organization
following the outbreak of foot and mouth disease. The enforcing body
(part of the local council) decided that there was insufficient
evidence to prosecute either IAH or Merial.
Conclusions:
High-containment laboratories provide facilities that are needed for
basic research, development of detection technologies, and diagnostic
and medical countermeasures for biothreats. Accordingly, facilities are
specialized and cannot easily be converted from one function to
another. Medium-to long-term advance planning for the appropriate
capacity levels is therefore essential, as is knowledge of existing
capacity. Such advance planning needs to take into account the (1)
projected future balance between biodefense and more traditional public
health work, (2) the specific infectious disease problems and targets
that the expansion is meant to address, and (3) targets for the
laboratory expansion's timetable or benchmarks as to when specific
capacities need to be available. We were unable to identify any
governmentwide strategic evaluation of these issues for high-
containment laboratories.
Furthermore, since no single agency is in charge of the current
expansion, no one is determining the associated aggregate risks posed
by the expansion. As a consequence, no federal agency can determine
whether high-containment laboratory capacity may now be less than,
meet, or exceed the national need or is at a level that can be operated
safely.
If an agency were tasked or a mechanism were established with the
purpose of overseeing the expansion of high-containment laboratories,
it could develop a strategic plan to (1) ensure that the number and
capabilities of potentially dangerous high-containment laboratories are
no greater or less than necessary, (2) balance the risks and benefits
of expanding such laboratories, and (3) determine the type of oversight
needed.
Such an agency or mechanism could analyze the biothreat problems that
need to be addressed by additional BSL-3 and -4 laboratories, the
scientific and technical capabilities and containment features that
such laboratories need to have, how the laboratories should be
distributed geographically, and how the activities of the laboratories
would be coordinated to achieve intended goals.
Standards for several key issues have not been developed. The agency or
mechanism responsible for overseeing the expansion of high-containment
laboratories could also be responsible for coordinating with the
scientific community to develop guidelines for high-containment
laboratory design, construction, and commissioning and training
standards for laboratory workers; providing definitions for exposure;
developing appropriate inventory control measures; and providing
guidance on the most efficient approach to personnel reliability
programs.
The oversight agency or mechanism could also address issues related to
the ongoing funding needs of high-containment laboratories. While NIAID
has provided funding to build RBLs and NBLs, these laboratories are
expected to compete for funding from NIH to sustain their research. It
is unclear what will happen to these facilities, their trained
personnel, and their technology if no such funding is available.
Further, as these facilities and other high-containment laboratories
age, adequate funding sources must be identified for upgrades and
maintenance, or the risks that they pose may outweigh their benefits.
Once laboratories have been commissioned and begin operating,
continuing maintenance and testing/validation programs are needed to
ensure that operating standards and regulatory compliance are
maintained. As facilities age, the costs of such programs will rise and
are likely to consume an increasing proportion of budgets. Although
this affects federal, industrial, and academic laboratories, the impact
is likely to be greatest on academic laboratories. Although federal
laboratories are subject to annual funding, they tend to have programs
that have long-term commitments and are not usually subject to major
changes even if principal investigators (scientists) relocate.
Industrial laboratories exhibit similar stability of operations once
they are committed to projects and programs. In all these cases,
maintenance budgets are less tied to funding for research than are
those of academic laboratories, which are highly dependent on research
grant funding to support both infrastructure maintenance as well as
research programs. Indeed, the two activities may compete for available
money. Relocation of a principal investigator who is the recipient of
research grant funding can create problems for the institute in
maintaining the laboratory facilities. Given the high costs of creating
high-containment laboratories, consideration also needs to be given to
the issue of their maintenance and support as distinct from funding for
research activity.
The four incidents at USAMRIID, TAMU, CDC, and Pirbright exemplify a
number of failures of systems and procedures that are meant, in
combination, to maintain the biosafety of high-containment laboratories
to protect laboratory workers and the public. DSAT and APHIS could
examine these incidents and apply the lessons learned across the
program.
These incidents have been described and analyzed in detail both because
they are recent and because detailed information was available about
the various factors involved. Unfortunately, the incidents and their
causal factors are not unique, and the scientific literature contains
information about many incidents occurring over decades that often
involved similar factors and the failure to maintain adequate
biosafety.
Overall, the safety record of high-containment laboratories has been
good, although a number of weaknesses have become apparent over time.
Consequently, along with expansion there needs to be a commensurate
development of both operational and oversight procedures to address
known deficiencies and, as far as practicable, proactively evaluate
future risks.
Laboratory operators, in collaboration with regulators, need to develop
and work through potential failure scenarios and use that information
to develop and put in place mechanisms to challenge procedures,
systems, and equipment to ensure continuing effectiveness.
Recommendations for Executive Action:
We recommend that the National Security Advisor, in consultation with
the Secretaries of Health and Human Services (HHS), Agriculture (USDA),
Defense (DOD), and Homeland Security (DHS); the National Intelligence
Council; and other executive departments as deemed appropriate identify
a single entity charged with periodic governmentwide strategic
evaluation of high-containment laboratories that will:
(1) determine:
* the number, location, and mission of the laboratories needed to
effectively meet national goals to counter biothreats;
* the existing capacity within the United States;
* the aggregate risks associated with the laboratories' expansion; and:
* the type of oversight needed:
and (2) develop, in consultation with the scientific community,
national standards for the design, construction, commissioning, and
operation of high-containment laboratories, specifically including
provisions for long-term maintenance.
We recommend that the Secretaries of HHS and USDA develop (1) a clear
definition of exposure to select agents and (2) a mechanism for sharing
lessons learned from reported laboratory accidents so that best
practices--for other operators of high-containment laboratories--can be
identified.
Should the Secretaries consider implementing a personnel reliability
program for high-containment laboratories to deal with insider risk, we
recommend that they evaluate and document the cost and impact of such a
program.
Recognizing that biological agent inventories cannot be completely
controlled at present, we also recommend that the Secretaries of HHS
and USDA review existing inventory control systems and invest in and
develop appropriate technologies to minimize the potential for insider
misuse of biological agents.
Agency Comments and Our Evaluations:
We obtained written comments on a draft of our report from the
Secretaries of HHS and USDA. The Executive Office of the President:
National Security Council did not provide comments. HHS and USDA
concurred with our recommendations that were directed to them (see
appendixes VII and VIII). HHS officials also provided general comments,
including some concerns that are discussed in appendix VII. In
addition, DOD, HHS, and USDA officials provided technical comments,
which have been addressed in the body of our report, as appropriate.
We are sending copies of this report to the Executive Office of the
President; the Attorney General; and the Secretaries of Agriculture,
Defense, Health and Human Services, and Homeland Security. In addition,
the report will be available at no charge on the GAO Web site at
[hyperlink, http://www.gao.gov].
If you or your staffs have any questions about this report, please
contact me at (202) 512-2700 or kingsburyn@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 report. GAO staff who made major contributions
to this report are listed in appendix IX.
Signed by:
Nancy Kingsbury, Ph.D.
Managing Director, Applied Research and Methods:
List of Requesters:
The Honorable Joseph I. Lieberman:
Chairman:
The Honorable Susan M. Collins:
Ranking Member:
Committee on Homeland Security and Governmental Affairs:
United States Senate:
The Honorable Henry A. Waxman:
Chairman:
The Honorable John D. Dingell, Jr.
Chair Emeritus:
The Honorable Joe Barton:
Ranking Member:
Committee on Energy and Commerce:
House of Representatives:
The Honorable Bart T. Stupak:
Chairman:
The Honorable Greg Walden:
Ranking Member:
Subcommittee on Oversight and Investigations:
Committee on Energy and Commerce:
House of Representatives:
The Honorable Darrell E. Issa:
Ranking Member:
Committee on Oversight and Government Reform:
House of Representatives:
The Honorable John F. Tierney:
Chairman:
The Honorable Jeff Flake:
Ranking Member:
Subcommittee on National Security and Foreign Affairs:
Committee on Oversight and Government Reform:
House of Representatives:
The Honorable Daniel E. Lungren:
Ranking Member:
Subcommittee on Emerging Threats, Cybersecurity, and Science and
Technology:
Committee on Homeland Security:
House of Representatives:
The Honorable Michael T. McCaul:
Ranking Member:
Subcommittee on Intelligence, Information Sharing and Terrorism Risk
Assessment:
Committee on Homeland Security:
House of Representatives:
The Honorable David E. Price:
Chairman:
Subcommittee on Homeland Security:
Committee on Appropriations:
House of Representatives:
The Honorable Richard Burr:
United States Senate:
The Honorable John Linder:
House of Representatives:
[End of section]
Appendix I: Scope and Methodology:
To determine the extent of expansion in the number of high-containment
laboratories and the areas experiencing growth, we interviewed agency
officials and experts and reviewed documents provided by agencies and
scientific literature. To determine which federal agency has the
mission to track and determine the aggregate risks associated with the
proliferation of BSL-3 and BSL-4 laboratories in the United States, we
surveyed 12 federal agencies that are involved with these laboratories
in some capacity--for example, research, oversight, or monitoring.
The survey requested information on whether the agency (1) has a
mission to track the number of high-containment laboratories, (2) has a
need to know the number of operating BSL-3 and BSL-4 laboratories, and
(3) knows that number. The agencies that received our survey included
the Department of Agriculture; the Department of Commerce; the
Department of Defense; the Department of Energy; the Environmental
Protection Agency; the Department of Health and Human Services,
including the Centers for Disease Control and Prevention (CDC); the
Department of Homeland Security; the Department of the Interior; the
Department of Justice, including the Federal Bureau of Investigation;
the Department of Labor, including the Occupational Safety and Health
Administration; the Department of State; and the Department of Veterans
Affairs. In addition, we sent our survey to intelligence agencies,
including the Central Intelligence Agency, the National Counter-
Terrorism Center, the Defense Intelligence Agency, and the Office of
Intelligence Analysis within DHS.
To supplement existing information on the current number of BSL-3 and
BSL-4 laboratories in the United States, we surveyed 724 individuals,
who were identified through various open sources as knowledgeable
contacts on biosafety laboratories, through a self-administered
electronic questionnaire posted on the World Wide Web between April
2007 and May 2007. We obtained responses from 295 respondents, for an
overall response rate of 41 percent. Several important limitations
should be noted about our survey. First, the universe of BSL-3 and -4
laboratories is unknown. While we used multiple sources to develop our
list of potential respondents, there are likely other laboratories that
we were unable to identify. Second, there may be duplicate responses in
cases where multiple persons responded to the survey for a single
institution. The data from our questionnaire are sufficiently reliable
to demonstrate that there are BSL-3 or -4 laboratories that do not work
with select agents.
We also met with officials of the Division of Select Agents and Toxins
and the Animal and Plant Health Inspection Service to gain additional
information about the expansion of high-containment laboratories.
Finally, we reviewed documents these agencies provided, including
pertinent legislation, regulations, and guidance, and reviewed
scientific literature on risks associated with high-containment
laboratories.
To develop lessons learned from recent incidents at four high-
containment laboratories, we interviewed academic experts in
microbiological research involving human, animal, and plant pathogens
and conducted site visits at selected federal, civilian, military,
academic, and commercial BSL-3 and BSL-4 laboratories, including the
sites involved in the recent incidents. Specifically, we conducted site
visits at CDC and Texas A&M University (TAMU); talked to United Kingdom
officials at the Health Safety Executive and the Department for
Environment, Food, and Rural Affairs; and reviewed documents and
inspection reports.
To discuss the incidents at TAMU and CDC, we conducted site visits and
interviewed the relevant officials. During our site visit to CDC, we
interviewed relevant officials, including the officials of CUH2A, Inc.--
the contractor who designed the backup power system for the new BSL-4
laboratory in Atlanta--as well as the expert hired by this firm to
conduct the reliability study for the backup power system.
We conducted our work from September 2005 through June 2009 in
accordance with generally accepted government auditing standards. Those
standards require that we plan and perform the audit to obtain
sufficient, appropriate evidence to provide a reasonable basis for our
findings and conclusions based on our audit objectives. We believe that
the evidence obtained provides a reasonable basis for our findings and
conclusions based on our audit objectives.
[End of section]
Appendix II: Expert Panel:
The expert panel that reviewed this report comprised scientists with
substantive expertise in microbiological and select agent research and
the operations of high-containment laboratories. The following were the
panel members:
Peter Emanuel, Ph.D.
Office of Science and Technology Policy:
Executive Office of the President:
Gigi Kwik Gronvall, Ph.D.
Center for Biosecurity of the University of Pittsburgh Medical Center:
University of Pittsburgh:
George V. Ludwig, Ph.D.
U.S. Army Medical Research and Material Command:
Ft. Detrick, Maryland:
Jack Melling, Ph.D., Retired:
U.K. Microbiological Research Authority:
Porton Down, United Kingdom:
Alan Jeff Mohr, Ph.D., Retired:
Life Sciences Division:
U.S. Army, Dugway Proving Ground:
Tooele, Utah:
Suresh D. Pillai, Ph.D.
Texas A&M University:
College Station, Texas:
Janet Shoemaker:
American Society for Microbiology:
Washington, D.C.
[End of section]
Appendix III: List of Select Agents and Toxins as of November 17, 2008:
HHS Select Agents and Toxins:
Abrin:
Botulinum neurotoxins:
Botulinum neurotoxin producing species of Clostridium:
Cercopithecine herpesvirus 1 (Herpes B virus):
Clostridium perfringens epsilon toxin:
Coccidioides posadasii/Coccidioides immitis:
Conotoxins:
Coxiella burnetii:
Crimean-Congo haemorrhagic fever virus:
Diacetoxyscirpenol:
Eastern Equine Encephalitis virus:
Ebola virus:
Francisella tularensis:
Lassa fever virus:
Marburg virus:
Monkeypox virus:
Reconstructed 1918 Influenza virus [Footnote 75]
Ricin:
Rickettsia prowazekii:
Rickettsia rickettsii:
Saxitoxin:
Shiga-like ribosome inactivating proteins:
Shigatoxin:
South American Haemorrhagic Fever viruses:
- Flexal:
- Guanarito:
- Junin:
- Machupo:
- Sabia:
Staphyloccoccal enterotoxins:
T-2 toxin:
Tetrodotoxin Tick-borne encephalitis complex (flavi) viruses:
- Central European Tick-borne encephalitis:
- Far Eastern Tick-borne encephalitis:
- Kyasanur Forest disease:
- Omsk Hemorrhagic Fever:
- Russian Spring and Summer encephalitis:
Variola major virus (Smallpox virus) and Variola minor virus (Alastrim)
Yersinia pestis:
USDA Select Agents and Toxins:
African horse sickness virus:
African swine fever virus:
Akabane virus:
Avian influenza virus (highly pathogenic):
Bluetongue virus (exotic):
Bovine spongiform encephalopathy:
Camel pox virus:
Classical swine fever virus:
Ehrlichia ruminantium (Heartwater):
Foot-and-mouth disease virus:
Goat pox virus:
Japanese encephalitis virus:
Lumpy skin disease virus:
Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1):
Menangle virus:
Mycoplasma capricolum subspecies capripneumoniae (contagious caprine
pleuropneumonia):
Mycoplasma mycoides subspecies mycoides small colony (MmmSC)
(contagious bovine pleuropneumonia):
Peste des petits ruminants virus:
Rinderpest virus:
Sheep pox virus:
Swine vesicular disease virus:
Vesicular stomatitis virus (exotic): Indiana subtypes VSV-IN2, VSV-IN3:
Virulent Newcastle disease virus[Footnote 76]
Overlap Select Agents and Toxins:
Bacillus anthracis:
Brucella abortus:
Brucella melitensis:
Brucella suis:
Burkholderia mallei (formerly Pseudomonas mallei):
Burkholderia pseudomallei (formerly Pseudomonas pseudomallei):
Hendra virus:
Nipah virus:
Rift Valley fever virus:
Venezuelan Equine Encephalitis virus:
USDA Plant Protection and Quarantine (PPQ) Select Agents and Toxins:
Peronosclerospora philippinensis (Peronosclerospora sacchari):
Phoma glycinicola (formerly Pyrenochaeta glycines):
Ralstonia solanacearum race 3, biovar 2:
Schlerophthora rayssiae var zeae:
Synchytrium endobioticum:
Xanthomonas oryzae pv. Oryzicola:
Xylella fastidiosa (citrus variegated chlorosis strain):
[End of section]
Appendix IV: Biological Agents Recommended for BSL-3 Containment That
Are Not Select Agents:
There are a number of biological agents causing severe illness or death
that are not select agents. Some non-select-agents are recommended for
work, research, and production safely under BSL-2 containment (BMBL,
5th Edition). These agents are listed in table 11. Several of these non-
select-agents may require BSL-3 containment for specific reasons,
including production of aerosols or large-scale production of these
organisms (BMBL, 5th Edition). These agents are listed in table 12.
Table 11: Agents Requiring BSL-2 Containment, Rarely BSL-3 Containment:
Agent: Bordetella pertussis;
Disease: pertussis (whooping cough)[A].
Agent: Neisseria gonorrhoeae;
Disease: gonorrhea.
Agent: M;
Disease: meningitis, septicemia.
Agent: Salmonella typhi;
Disease: typhoid fever[A].
Agent: Hepatitis B, C, D viruses;
Disease: hepatitis B[A] , hepatitis C, hepatitis D.
Agent: Human herpes virus;
Disease: herpes simplex et al.
Agent: Lyssaviruses;
Disease: rabies[A].
Agent: Retroviruses;
Disease: HIV.
Source: BMBL, 5th Edition.
[A] These agents currently have vaccines available to the public.
[End of table]
Table 12: Agents Typically Requiring BSL-3 Containment:
Agent: Chlamydia psittaci;
Disease: psittacosis.
Agent: Hanta virus;
Disease: Hanta virus pulmonary syndrome.
Agent: Mycobacterium tuberculosis complex;
Disease: tuberculosis.
Agent: Non-contemporary human influenza Strains (H2N2);
Disease: H2N2 influenza.
Agent: Lymphocytic choriomeningitis virus;
Disease: aseptic meningitis, encephalitis.
Agent: SARS coronavirus;
Disease: SARS[A].
Agent: West Nile virus;
Disease: "West Nile virus" encephalitis.
Source: BMBL, 5th Edition.
[A] CDC has proposed that this agent be added to the select agents and
toxins list.
[End of table]
[End of section]
Appendix V: The Army's Requirements for High-Containment Laboratories
in 2001:
According to DOD officials, DOD did not have a policy document specific
to biological select agents and toxins (BSAT) or high-containment
laboratories in 2001.
In 2001, all U.S. Army high-containment laboratories working with
select agents were registered with CDC (under 42 C.F.R. § 72.6). Army
safety regulations in place at that time required the following:
1. A hazard analysis must be conducted to determine safety precautions,
necessary personnel protection, engineering features, and procedures to
prevent exposure for all agents. The Army utilized the risk analysis
technique of maximum credible events, which examines the consequences
of realistic worst-case scenarios.
2. Facilities must have standard operating procedures, training and
proficiency requirements, medical surveillance, emergency preparedness
procedures (including advance notification to local, state, regional,
and federal emergency response personnel), hazard labeling, disposal
and maintenance controls, and protective equipment for all work with
agents.
3. Quarterly inspections for biosafety level (BSL)-1 and BSL-2
laboratories and monthly inspections for BSL-3 and BSL-4 laboratories
must be conducted.
4. All mishaps must be reported and investigated. Medical surveillance
of all workers present must begin immediately after a mishap.
5. Access control procedures were required to keep people not needed to
operate biological laboratories from entering.
6. Federal, state, and local laws must be obeyed when transporting
agents.
7. Components that contract out biological defense work must prepare
written procedures that set guidelines for facilities, safety,
inspections, and risk analysis. They were also required to monitor
contractor performance in meeting safety requirements, which includes
pre-award inspections, annual inspections of BSL-3 facilities and
semiannual inspections of BSL-4 facilities, documentation of safety
training programs, designation of an individual responsible for safety,
and storage and disposal procedures. Contractors working at BSL-3 and
BSL-4 facilities must prepare a plan for controlling laboratory
mishaps.
8. Facilities must have published safety plans and monitoring
procedures that they coordinated with federal, state, and local
emergency services and practiced with emergency groups. An occupational
health program, including medical surveillance examinations, was also
required.
9. The regulations also set out operational requirements, including
laboratory techniques, based on biosafety level, and emergency
procedures, such as establishing evacuation procedures and an emergency
alarm system.
10. Facilities must abide by personal protective equipment requirements
(based on biosafety level), decontamination and disposal requirements
and shipping restrictions, and facility specifications based on
biosafety level and engineering controls.
These regulations are located at 32 C.F.R., parts 626 and 627. Army
pamphlet 385-69 also prescribes the minimum safety criteria and
technical requirements and is used in conjunction with these
regulations.[Footnote 77] Additionally, since USAMRIID was designated a
"restricted area" in 1995, a National Agency Check was also required
for general unescorted access for all staff. The USAMRIID Special
Immunizations Clinic provided baseline medical and occupational health
evaluations of fitness to work in the laboratories and provided
vaccines. Annual medical interviews, physical exams, and laboratory
reassessments were conducted for changes in health, medication, and
duties.
According to information provided to us by USAMRIID, security clearance
was not and is not required to work in high-containment laboratories,
and having a security clearance did not by itself allow access to high-
containment laboratories. In 2001, there was no centralized requirement
for inventory control and accountability. Individual scientists
maintained their own stocks and accountability.
CDC's regulations in 2001 (42 C.F.R. § 72.6) focused on the transfer of
select agents and thus did not focus on personnel security or insider
risk or inventory control of select agents. While Army regulations
required that the consequences of realistic worst case scenarios be
examined, insider risk was not considered in such examinations.
[End of section]
Appendix VI: CDC's Integrated Approach to Biocontainment at High-
Containment Laboratories:
In commenting on the draft report, HHS officials stressed the
importance of the Centers for Disease Control and Prevention's (CDC)
integrated "three-legged approach" to biocontainment at high
containment laboratories. They provided the following technical details
of their biocontainment experiences.
"According to CDC officials, monitoring one-pass directional airflow
through negatively pressurized containment zones, enclosed and
separated by airtight doors and structure, with HEPA filtration on both
the supply side (one HEPA filter) and the exhaust side (two HEPA
filters), along with robust Operations and Maintenance protocols (O&M)
provides a sound facility design and construction component for CDC's
'three-legged' approach to biocontainment. This approach, which is
described in Section II of the BMBL, stresses that laboratory practice
and technique is the most important element of a comprehensive
containment strategy, in conjunction with appropriate safety equipment
(as a primary barrier) and facilities design/construction and
engineering (as a secondary containment barrier). CDC maintains that
while directional airflow and negative pressure in BSL-4 laboratories
is a critical engineering component of a normal 'safe' operating
environment, engineering systems do fail from time-to-time, for various
reasons.
"In the event of a loss of power to the supply and exhaust fans and
controls that maintain negative pressure conditions in CDC's BSL-4
laboratories, the laboratories go to a 'static pressure' status,
whereby secondary containment is maintained by the airtight door
gaskets, airtight construction of interior walls, floors, and ceiling
within the BSL-4 laboratory block, and because the HEPA filters on the
supply side and exhaust ducts are functionally impermeable to air for
certain periods of time under static pressure conditions. In effect
proper design, construction and O&M render the CDC BSL-4 laboratories
into airtight boxes during a complete loss of normal and standby power
during these events. Containment was also preserved because CDC's
laboratorians are properly trained in safe laboratory practices and
procedures, and BSL equipment and safety protocols (primary barriers)
functioned as intended. Equipment within the BSL-4 laboratories include
biological safety cabinets, centrifuges, and heavy-duty personal
protective suits (i.e., 'space suits').
"In the lightning and bird strike incidents outlined above [see pp. 58-
61], secondary engineering controls failed due to temporary
construction-related impacts, rather than typical operations
conditions, and all but UPS-generated life safety required power was
lost in B [building] 18. However, because CDC had appropriated and
effective laboratory practice and safety equipment and practices in
place, and because a static pressure condition had been maintained (as
a secondary barrier), the chance of an accidental release of dangerous
pathogens into the environment so as to cause a significant risk to CDC
workers or the surrounding community did not exist.
"According to CDC officials, the lightning and bird strike incidents
are not typical of O&M-related incidents that CDC has experienced over
the years since they are directly related to the intense construction
activities at the Roybal Campus that have been ongoing since
approximately 2000, and are expected to largely conclude in
approximately 2011. The construction activities are the execution of
the Agency's 10-Year Master Plan to replace the many 50-year old
buildings, including laboratories and infrastructure at the Roybal and
Chamblee Campuses. CDC date [data] indicates that even with the
lightning and bird strike incidents, the Roybal Campus electrical
distribution system has had a 99.9997 percent reliability rate, or
approximately 10 hours of documented down-time due to power outages
during 78,840 hours of total run time (2000-2008). CDC expects to
reduce electrical system downtime once construction activities have
ceased."
[End of section]
Appendix VII: Comments from the Department of Health and Human
Services:
Note: GAO comments supplementing those in the report text appear at the
end of this appendix.
Department Of Health & Human Services:
Office Of The Secretary:
Assistant Secretary for Legislation:
Washington, DC 20201:
July 20, 2009:
Nancy Kingsbury, Ph.D.
Managing Director:
Applied Research and Methods:
U.S. Government Accountability Office:
441 G Street N.W.
Washington, DC 20548:
Dear Ms. Kingsbury:
Enclosed are comments on the U.S. Government Accountability Office's
(GAO) report entitled: "HIGHCONTAINMENT LABORATORIES: Coordinated
National Oversight is Needed" (GAO-09-574).
The Department appreciates the opportunity to review this report before
its publication.
Sincerely,
Signed by:
Barbara Pisaro Clark:
Acting Assistant Secretary for Legislation:
Attachment:
[End of letter]
General Comments From The Department Of Health And Human Services (HHS)
On The Government Accountability Office's (GAO) Draft Report Entitled,
"High-Containment Laboratories: Coordinated National Oversight Is
Needed" (GAO-09-574):
The Department of Health and Human Services (HHS) thanks GAO for the
opportunity to review and comment on this draft report. HHS concurs
with GAO's recommendations that have been directed to the Secretary of
HHS and respectfully submits the following comments about the report.
Knowing the Total Number of All BSL-3 Laboratories Could be Beneficial
But Has Not Been Mandated
In the section titled, "BSL-3 Labs Are Being Built in All Sectors
Throughout the United States," GAO implies that the Centers for Disease
Control and Prevention (CDC) should know the total number Biosafety
Level-3 laboratories (BSL-3 laboratories) in the United States. [See
comment 1] Though it could be beneficial to know where all the BSL-3
laboratories are located across the country, it is important to point
out prominently in this report that there is no executive or
legislative mandate directed at any federal agency to know this
information. The select agent programs at CDC and the United States
Department of Agriculture (USDA)/Animal and Plant Health Inspection
Service (APHIS) know the identity and location of all laboratories (BSL-
2, BSL-3, and BSL-4) that possess, use, or transfer select agents,
which is a tremendous data resource. They maintain this information
because it was required by the Public Health Security and Bioterrorism
Preparedness and Response Act of 2002. However, there is no such
reporting requirement for laboratories that do not work with select
agents. Knowing information about the location of all BSL-3
laboratories could be beneficial, but instituting new regulatory
reporting requirements possibly could create a burden on private sector
laboratories and would require new federal resources. To this end, HHS
will recommend to appropriate entities to engage in a more in-depth
policy debate on this issue. [See comment 2]
Suggestions for Presenting Information About Power Outages at CDC:
Because it does not appear that the report includes some important
details that were provided in previously submitted responses, comments,
and other written documents, HHS does not concur with GAO's assessment
of Incident 3 and GAO's related findings. [See comment 3]
We urge GAO to point out that the lightning strike that occurred on
June 8, 2007 on CDC's campus affected BSL-4 laboratories that were not
yet operational; no laboratory work of any kind had been conducted
inside the BSL-4 laboratories in Building 18 prior to the lightening
strike incident. In addition, no infectious pathogens were stored in
this space because the commissioning process was still ongoing and the
laboratories were not yet activated. It is important to note that there
was never a threat to any laboratory workers, CDC employees, or the
public. Conveying this information is critical so that readers will
have a clear understanding about the outage.
We also urge GAO to note that even if the laboratories had been
operational, there still would not have been any threat of exposure to
any laboratory workers, CDC employees, or the public. The draft report
currently does not discuss a very important facility design approach
that ensures biocontainment, which is an approach that is embraced by
CDC and implemented in the design and operations of the Building 18
high-containment laboratory. This approach is the "multi-tiered," or
integrated "three-legged" containment, method that stresses three
components: (1) laboratory practice and technique; (2) appropriate
safety equipment as a primary containment barrier; and (3) facilities
design, construction, and engineering as a secondary containment
barrier.
The approach, which is described in Section II of Biosafety in
Microbiological and Biomedical Laboratories 5s` edition (BMBL),
stresses that laboratory practices and techniques are the most
important elements of a comprehensive containment strategy. CDC
maintains that all three components are necessary when analyzing the
effectiveness of biocontainment in BSL laboratories and that no single
component failure will necessarily constitute the loss of containment.
Although this detail was covered during meetings with GAO and would be
beneficial to include, this information is not currently reflected in
the report.
We do question GAO's assessment that problems with primary power
failures of BSL-4 laboratories could have "devastating consequences"
(Lessons Learned section for Incident 3). Because it is unclear how GAO
defines "devastating," it may be overstating the problem about the
impact of a loss of power. All air in a BSL-4 laboratory is filtered
before entering both the inside and outside environments and the
workers in the laboratory are protected from aerosols through the
positive pressure suits or sealed biological safety cabinets. Please
note that the systems are designed to maintain containment, and many
system components are redundant and overlapping. Thus, the loss of one
component does not necessarily result in loss of overall containment.
[See comment 4]
Also, the draft report should include several important details
regarding the critical differences, purpose, and functions
differentiating code-required emergency power and legally required
standby power. These differences are important when planning and
designing electrical distribution systems for biological laboratories
and other science buildings and should be carefully considered when
performing an analysis of such a system. Comments and other written
data concerning this topic were provided to GAO. [See comment 5]
Serological Testing Can Indicate an Exposure if Interpreted Properly:
In discussing the Texas A&M University incident, the GAO report
addresses the issue of using serological testing to monitor potential
exposures to select agents. When used properly, serological testing can
be an effective method for detecting exposures to infectious agents,
including select agents. A serum titer that is higher than a baseline
titer is not necessarily considered an exposure. The rise in titer is
the most important aspect of identifying infection, assuming that a pre-
exposure serum is also tested. The titer should be at least 4 times
higher than a baseline to be considered an exposure, and the timeframe
in which the testing was done (relative to the baseline) is also
important. Antibody titers generally rise after clinical symptoms
appear. Many nuances to the proper interpretation of serological
testing exist (e.g., the appropriate use and interpretation of these
tests; and identification of type of antibody [IgM and IgG]). All of
these factors need to be considered to best interpret serological
testing. Before finalizing findings and conclusions on this issue, GAO
may find it helpful to get assistance from specialists in serological
testing. [See comment 6]
The report also indicates that more guidance is needed for the
regulated community in using this method. CDC and APHIS jointly
developed the Select Agents and Toxins Theft, Loss and Release
Information Document to provide guidance to the regulated community on
what constitutes an occupational exposure to a select agent, including
guidance on the interpretation of serological testing [hyperlink,
http://www.selectagents.gov/resources/CDC-
APHIS_Theft_Loss_Release_Information_Document.pdf].
However, the Select Agents and Toxins Theft, Loss and Release
Information Document is not the only tool used by the HHS and USDA
select agent programs to communicate with registered entities on
occupational health issues such as serological testing: As part of the
oversight process, select agent programs routinely review occupational
health plans. In addition, select agent liaisons are routinely
available to discuss occupational health issues with responsible
officials and other members of the regulated community.
Recommendations for the National Security Advisor:
HHS is committed to working with the National Security Advisor should a
government-wide, strategic evaluation of high-containment laboratories
be undertaken.
To inform this discussion, we note that national goals to counter
biothreats may change over time. Laboratories are built to last 50
years or longer, so assessing whether current laboratory capacity will
be appropriate for future needs is difficult. A BSL-3 laboratory can be
used for BSL-2 work, but it is impossible, without renovating it, to
use a BSL-2 laboratory for BSL-3 work. Therefore, it is more desirable
to build for the maximum biosafety containment that is anticipated
(e.g., BSL-3) while using a realistic estimate for future needs (e.g.,
more than 50 years). Otherwise, it would be impossible to work with
highly pathogenic microorganisms-such as severe acute respiratory
syndrome (SARS)-quickly. One may need to reconsider the suggestion that
an oversight organization could address the needs and distribution of
laboratories, and coordinate the intended goals, because the needs will
change yearly. Coordination may not be easy because federal agencies
have different agendas, timelines, and budgets. [See comment 7]
The issue of how many laboratories should exist and where these
laboratories should be located is complex. It is important to consider
the uses of such laboratories in the future. For example, having a BSL-
3 laboratory available in an institution is considered a bonus when it
needs to be used quickly for new and emerging needs such as SARS. It is
essential to have laboratory capacity for optimizing emergency response
and public health threats. However, the overall need should be
determined by taking into account the ability to respond effectively
and quickly to natural and manmade infectious-disease emergencies
across a wide region or area; the ability to create new science around
the identification, characterization, and control of re-emerging or
novel infectious-disease threats; and the ability to quickly develop
appropriate countermeasures.
This report may not identify all gaps in high-containment laboratory
facilities in clinical settings, including large community hospitals
and tertiary-care facilities. Many believe that these types of clinical
facilities often have inadequate containment measures for certain high-
risk work. Expansion of laboratories does not automatically mean that
too many laboratories exist, nor does it mean that the distribution and
supply of existing high-containment laboratories is adequate or
optimum. Any future evaluations of capacity and supply should examine
the needs of the clinical laboratories related to their high-
containment capacity. [See comment 8]
GAO recommends that the National Security Advisor identify a single
entity to evaluate high containment laboratories. This entity should
not only validate the number and capacity of the laboratories (to
determine whether these factors are appropriate and meet the needs of
the country), but identify the risks and determine what kind of
oversight is needed.
Regarding the concern of risks associated with expanding high-
containment laboratories and their resulting capacity, such risks
should be carefully balanced by (1) the rewards associated with the
enhanced epidemiology and surveillance capacity; (2) the improved
ability to respond to emergencies; and (3) the improved ability to
mitigate outbreaks and control infectious diseases.
An amazing success story is the expansion of the Laboratory Response
Network (LRN) during the past decade: now all 50 states, the District
of Columbia, and several territories have BSL-3 capabilities. This
development has been crucial in ensuring a safer and more robust
response capability, and it has clearly enhanced our ability to
identify, characterize, and respond to public health threats.
Specifically, the LRN has greatly enhanced our response to seasonal
influenza, H5N1, SARS, white-powder and toxin events, threat letters,
and novel H1N1 influenza A virus.
GAO also recommends that there be a government-wide effort to develop
national standards for designing, constructing, commissioning, and
operating high-containment laboratories. Some national standards for
design, construction, commissioning, and operation of these
laboratories have been included in the BMBL. However, it may be more
beneficial to share lessons learned in the trade than to create
standards, which may not apply in all situations. In addition, many of
these laboratories are already constructed and being maintained, so it
would need to be determined how such standards would apply to them.
[See comment 10]
Recommendations for the Secretary of HHS:
GAO Recommendation: We recommend that the Secretaries of HHS and USDA
develop (1) a clear definition of exposure to select agents; and (2) a
mechanism for sharing lessons learned from reported laboratory
accidents so that best practices can be identified and shared with
other operators of high containment laboratories.
HHS Response: HHS agrees that it is important for select-agent
registered entities to have a clear understanding of what constitutes
an exposure to select agents. CDC's and APHIS' select agent programs
have seriously considered the issue of select agent exposures. The
APHIS/CDC Select Agents and Toxins Theft, Loss and Release Information
Document that was published on January 18, 2009, contains a definition
for occupational select agent exposures [Hyperlink,
http://www.selectagents.gov/resources/CDCAPHIS_Theft_Loss_Release_Inform
ation_Document.pdf]. This definition, which is derived from the
occupational exposure definition in the OSHA Bloodborne Pathogens
Standard (29 CFR Part 19101030b), is as follows:
"Occupational exposure: Any event which results in any person in a
registered entity facility or lab not being appropriately protected in
the presence of an agent or toxin. This may include reasonably
anticipated skin, eye, mucous membrane, or parenteral contact with
blood or other potential infectious materials that may result from the
performance of a person's duties. For example, a sharps injury from a
needle being used in select agent or toxin work would be considered an
occupational exposure."
The Select Agents and Toxins Theft, Loss and Release Information
Document will also assist the regulated community in analyzing
incidents for select agent exposures. Through 20 possible scenarios, it
describes how this definition is applied to incidents that may occur in
select agent facilities. We will review the Select Agents and Toxins
Theft, Loss and Release Information Document and consider adding the
occupational health response recommendations in Scenario 20.
HHS also agrees that lessons learned from laboratory accidents should
be synthesized and shared with the broader laboratory community. The
APHIS/CDC Form 3 collects information on thefts, losses, and releases
of select agents. CDC will work with APHIS to synthesize the data that
have been gathered about releases in laboratories registered with the
select agent programs, and it will publish and share this analysis in a
public report. Please note that HHS and USDA have the ability to gather
such data only for laboratories that work with select agents. A
separate mechanism must be identified to gather information about
releases in laboratories that do not work with select agents.
GAO Recommendation: Should the Secretaries consider implementing a
personnel-reliability program for high-containment laboratories to
address insider risk, we recommend that they evaluate and document the
cost and impact of such a program.
HHS Response: HHS agrees that there must be a careful analysis of the
costs, risks, and benefits of personnel-reliability programs before
such a requirement is instituted for the select agent program. The
Working Group on Strengthening the Biosecurity of the United States,
established by Executive Order 13486 and signed by President George W.
Bush on January 9, 2009, also addresses this issue. The draft report
was provided to the White House on July 9, 2009. HHS will work with its
partners at USDA to carefully evaluate the value, feasibility, cost,
and impact of implementing such a program. As part of the evaluation,
HHS and USDA will consider the recommendations from this working group
regarding personnel-reliability programs.
GAO Recommendation: Recognizing that biological agent inventories
cannot be completely controlled right now, we also recommend that the
Secretaries of HHS and USDA review existing inventory-control systems
and invest in and develop appropriate technologies to help minimize the
potential risk for an insider to misuse biological agents.
HHS Response: HHS agrees that inventory-control systems must be
improved to minimize the potential risk for an insider to misuse
biological agents. The Select Agent Regulations include requirements
related to maintaining inventory logs of select agents. However, some
have called for additional guidance from the select agent programs on
requirements related to working stocks versus select agents that are
held long term in storage. CDC's and APHIS' select agent programs have
worked together to provide registered entities with additional guidance
on the inventory requirements for working stocks and select agents that
are held long term in storage. On February 12, 2009, CDC's and APHIS'
select agent programs posted guidance on the definition of "long-term
storage" as used in the Select Agent Regulations. This guidance is
available on the National Select Agent Program's website at the
following address: [hyperlink,
http://www.selectagents.gov/complianceAssistance.htm]. Also, we will
carefully review any recommendations regarding inventory control from
the Working Group on Strengthening the Biosecurity of the United States
and consider how to implement those recommendations.
The following are GAO's responses to the Department of Health and Human
Service's (HHS) comments in a letter dated July 20, 2009.
GAO Comments:
1. We agree with HHS. Our report acknowledges that no executive or
legislative mandate currently requires any agency to gather this
information and we are making a recommendation in this regard.
2. We agree that instituting new regulatory reporting requirements
about the location of all BSL-3 laboratories could create a burden on
private sector laboratories and would require new federal resources.
3. Our report did acknowledge information from CDC officials stating
that at the time of both incidents, the new BSL-4 facility was not
fully operational and that no agents were inside the facility. However,
we believe that CDC is missing the point. Given that grounding cables
were cut, it is apparent that the building's integrity as it related to
adjacent construction was not adequately supervised. CDC officials
stated that standard procedures under building codes did not require
monitoring of the integrity of the new BSL-4 facility's electrical
grounding. This incident highlighted the risks inherent in relying on
standard building codes to ensure the safety of high-containment
laboratories--as there are no building codes and testing procedures
specifically for those laboratories. We agree with CDC that high-
containment laboratories include a three-legged and multi-tiered
approach to containment. However, to have a fully safe system of
containment, any failure of one tier or one of the legs needs to be
rapidly identified and corrected. Our focus in this incident was on
CDC's power system and lessons that can be learned for other high-
containment labs.
4. We modified the language in our report to note that a loss of power
could have serious consequences under certain circumstances.
5. While we agree that critical differences, purposes, and functions
differentiating code-required emergency power and legally required
standby power are important when planning and designing electrical
distribution systems for biological laboratories and other science
buildings, this does not materially affect our findings.
6. We disagree with CDC that the titer should be at least four times
higher than the baseline level to be considered an exposure. Most
importantly, any increase in titers involving an agent that is being
worked on at a laboratory should be taken seriously and investigated.
The laboratory safety aspect of antibody titers is clearly different
from those that apply to a general clinical situation. The increase in
titers may indicate natural exposure to the agent (depending on the
agent and location of the lab) or result from inconsistencies
associated with laboratory testing. Most serological assays for select
agents are not commonly conducted in clinical laboratories and are
primarily performed in research laboratories. As such, these assays may
not be properly controlled and validated. Assay-to-assay variation may
be high, especially if experience is limited. Additionally, such assays
are not particularly robust unless baseline specimens are available for
comparison testing and serum samples are collected within relatively
short time frames (for example, 3 to 6 months).
7. We agree with HHS that national goals may change over time.
Therefore, it is important that the strategic evaluation of high-
containment laboratories be undertaken periodically. We have modified
our recommendation to include periodic evaluation.
8. Our report recommends that a single entity be charged with
governmentwide strategic evaluation of high-containment laboratories.
While we agree that there are several challenges, having a single
agency would facilitate a coordinated response.
9. We agree that future evaluations of laboratory capacity and supply
should examine the needs of the clinical laboratories related to their
high-containment capacity. However, knowing the number of laboratories
is a key requirement to making such evaluation effective.
10. We disagree. We believe that national standards contribute to
ensuring that all high-containment laboratories meet minimum standards.
National standards are valuable not only in relation to new laboratory
construction but also in ensuring compliance for periodic upgrades. We
agree that BMBL provides guidance on design and construction; however,
the guidance does not provide standards that must be adhered to. While
sharing lessons learned can be beneficial to meeting standards, it is
not an adequate substitute for the standards themselves. If existing
laboratories do not meet national standards, we believe that these
laboratories need to be brought into compliance.
[End of section]
Appendix VIII: Comments from the Department of Agriculture:
USDA:
United States Department of Agriculture:
Office of the Secretary:
Washington, DC 20250:
August 19, 2009:
Dr. Sushil Sharma, Assistant Director:
Applied Research and Methods:
Center for Technology and Engineering:
U.S. Government Accountability Office:
441 G Street, NW:
Washington, DC 20548:
Dear Dr. Sharma:
The U.S. Department of Agriculture (USDA) appreciates the opportunity
to review and provide comments on the GAO Draft Report, "High
Containment Laboratories: Coordinated National Oversight Is Needed" (09-
574). We have addressed the Recommendations for Executive Action that
pertain to USDA.
GAO Recommendation:
We recommend that the National Security Advisor, in consultation with
the Secretaries of Health and Human Services, Agriculture, Defense, and
Homeland Security; the National Intelligence Council; and other
executive departments as deemed appropriate identify a single entity
charged with governmentwide strategic evaluation of high-containment
labs that will (1) determine the number, location, and mission of the
labs needed to effectively meet national goals to counter biothreats;
the existing capacity within the United States; the aggregate risks
associated with the labs' expansion; and the type of oversight needed;
and (2) develop, in consultation with the scientific community,
national standards for the design, construction, commissioning, and
operation of high-containment labs, specifically including provisions
for long-term maintenance.
USDA Response:
USDA agrees with this Recommendation, and will work with the National
Security Advisor and other agencies to determine the appropriate body
that should he charged with governmentwide strategic evaluation for
high-containment labs. Further, USDA will also work cooperatively on
establishing national standards for the design, construction,
commissioning, and operation of high-containment laboratories.
Two interdepartmental work groups have also reviewed issues related to
oversight of high- and maximum-containment laboratories. The Trans-
Federal Task Force on Optimizing Biosafety and Biocontaiment Oversight
(co-chaired by USDA and the Department of Health and Human Services
(HHS)) focused its evaluation on Federal facilities, while the
Biosecurity Working Group (formed in response to Executive Order 13486,
"Strengthening Laboratory Biosecurity in the United States,") focused
on security and personnel reliability for Federal, State, and private
facilities. The Trans-Federal Task Force, and the Biosecurity Working
Group will be submitting their recommendations to Congress and the
White House on similar issues. The recommendations submitted from these
evaluations may affect the scope of work discussed in these GAO
recommendations.
GAO Recommendation:
We recommend that the Secretaries of Health and Human Services and
Agriculture develop (1) a clear definition of exposure to select agents
and (2) a mechanism for sharing lessons learned from reported lab
accidents so that best practices for other operators of high-
containments labs can be identified.
USDA Response:
USDA agrees with this Recommendation. However, USDA believes that the
Federal Select Agent Program (i.e., HHS' Centers for Disease Control
and Prevention's (CDC) Division of Select Agents and Toxins, and USDA's
Animal and Plant Health Inspection Service's (APHIS) Agriculture Select
Agent Program) has provided a sufficiently clear definition of
occupational exposure: "any event which results in any persons in a
registered entity, facility or lab not being appropriately protected in
the presence of an agent or toxin. This may include reasonably
anticipated skin, eye. mucous membrane, or parenteral contact with
blood or other potential infectious materials that may result from the
performance of a person's duties. For example, a sharps injury from a
needle being used in select agent or toxin work would be considered an
occupational exposure." This definition is derived from the
Occupational Safety and Health Administration Bloodborne Pathogens
Standard in title 29, Code of Federal Regulations (29 CFR), part 1910-
1030h) and is jointly published in the "Select Agents and Toxins Theft,
Loss and Release Information Document," dated January 18, 2008. The
document is currently posted on the Federal Select Agent Web site.
USDA agrees with GAO that reported laboratory incidents can be
summarized and published in a format that can help other entities learn
from the incidents. USDA's APHIS will work with CDC to develop and
complete an effective process, by December 2010.
GAO Recommendation:
Should the Secretaries consider implementing a personnel reliability
program for high containment labs to deal with insider risk, we
recommend that they evaluate and document the cost and impact of such a
program.
USDA Response:
USDA agrees with this Recommendation. Should the Secretary of USDA
consider implementing a personnel reliability program as part of our
regulatory responsibilities, we will evaluate and document the cost and
impact of such a program. The Biosecurity Working Group will address
the issue of implementing personnel reliability programs in high-
containment laboratories, and will provide additional information and
possible recommendations on personnel reliability programs to be
implemented in registered facilities.
Further, USDA currently has a personnel reliability program for its own
laboratories, as outlined in "USDA Departmental Manual 9610-001: USDA
Security Policies and Procedures for Biosafety Level - 3 Facilities,"
which sets the policy on suitability requirements for USDA and non-USDA
personnel requiring access to BSL-3 facilities. This document will soon
be revised. However, as stated before, should USDA implement a new
personnel reliability program, the agency will consider the cost and
impact of such a program.
GAO Recommendation:
Recognizing that biological agent inventories cannot be completely
controlled at present, we also recommend that the Secretaries of Health
and Human Services and Agriculture review existing inventory control
systems and invest in and develop appropriate technologies to minimize
the potential for insider misuse of biological agents.
USDA Response:
USDA agrees with this Recommendation, and will review inventory control
systems used by regulated laboratories and other laboratories working
with pathogens. The Biosecurity Working Group has addressed inventory
control systems in its review, and its report will probably include
some recommendations on this issue. USDA and HHS will review existing
inventory control systems within the context of the Federal Select
Agent Program by December 2010 and will decide, by December 2011,
whether to change existing regulations.
Pertinent to the issue of inventory control, the Federal Select Agent
Program has developed a guidance document on long-term storage. This
document, "Guidance on the Definition of Long Term Storage as Used in
the Select Agent Regulations." is posted on the Federal Select Agent
Program Web site. Based on comments from multiple public meetings, the
document will be expanded to include more specific guidance on working
stocks, inventory procedures. and examples of inventory systems. We
will have this guidance updated by December 2010.
Sincerely,
Signed by:
Ann Wright:
Deputy Under Secretary:
Marketing and Regulatory Programs:
[End of section]
Appendix IX: GAO Contact and Staff Acknowledgments:
GAO Contact:
Nancy Kingsbury, (202) 512-2700 or kingsburyn@gao.gov:
Staff Acknowledgments:
In addition to the contact named above, Sushil Sharma, Ph.D., Dr PH
(Assistant Director), Amy Bowser, George Depaoli, Terrell Dorn, Jeff
McDermott, Jean McSween, Jack Melling, Ph.D., Corey Scherrer, Linda
Sellevaag, and Elaine Vaurio made key contributions to this report.
[End of section]
Related GAO Products:
Biological Research: Observations on DHS's Analyses Concerning Whether
FMD Research Can Be Done as Safely on the Mainland as on Plum Island
[hyperlink, http://www.gao.gov/products/GAO-09-747]. Washington, D.C.:
July 30, 2009.
Biosafety Laboratories: BSL-4 Laboratories Improved Perimeter Security
Despite Limited Action by CDC. [hyperlink,
http://www.gao.gov/products/GAO-09-851]. Washington, D.C.: July 7,
2009.
Biosafety Laboratories: Perimeter Security Assessment of the Nation's
Five BSL-4 Laboratories. [hyperlink,
http://www.gao.gov/products/GAO-08-1092]. Washington, D.C.: September
17, 2008.
High-Containment Biosafety Laboratories: DHS Lacks Evidence to Conclude
that Foot-and-Mouth Disease Research Can be Done Safely on the U.S.
Mainland. [hyperlink, http://www.gao.gov/products/GAO-08-821T].
Washington, D.C.: May 22, 2008.
High-Containment Biosafety Laboratories: Preliminary Observations on
the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in
the United States. [hyperlink,
http://www.gao.gov/products/GAO-08-108T]. Washington, D.C.: October 4,
2007.
Biological Research Laboratories: Issues Associated with the Expansion
of Laboratories Funded by the National Institute of Allergy and
Infectious Diseases. [hyperlink,
http://www.gao.gov/products/GAO-07-333R]. Washington, D.C.: February
22, 2007.
Homeland Security: Management and Coordination Problems Increase the
Vulnerability of U.S. Agriculture to Foreign Pests and Disease.
[hyperlink, http://www.gao.gov/products/GAO-06-644]. Washington, D.C.:
May 19, 2006.
Plum Island Animal Disease Center: DHS and USDA Are Successfully
Coordinating Current Work, but Long-Term Plans Are Being Assessed.
[hyperlink, http://www.gao.gov/products/GAO-06-132]. Washington, D.C.:
December 19, 2005.
Homeland Security: Much Is Being Done to Protect Agriculture from a
Terrorist Attack, but Important Challenges Remain. [hyperlink,
http://www.gao.gov/products/GAO-05-214]. Washington, D.C.: March 8,
2005.
Combating Bioterrorism: Actions Needed to Improve Security at Plum
Island Animal Disease Center. [hyperlink,
http://www.gao.gov/products/GAO-03-847]. Washington, D.C.: September
19, 2003.
Homeland Security: CDC's Oversight of the Select Agent Program.
[hyperlink, http://www.gao.gov/products/GAO-03-315R]. Washington, D.C.:
November 22, 2002.
[End of section]
Footnotes:
[1] Some use the term high-and maximum-containment laboratories to
refer to BSL-3 and BSL-4 laboratories. The terms animal biosafety level
(ABSL)-3 and ABSL-4 are used for laboratories that work with animals
infected with indigenous or exotic agents. The term BSL-3 Ag is used to
describe laboratories where studies are conducted employing large
agricultural animals. However, for purposes of this report, we are
using the term high-containment laboratories to refer to all these
laboratories.
[2] In the wake of the 2001 terrorist attacks, the National Institutes
of Health (NIH) convened the Blue Ribbon Panel on Bioterrorism and Its
Implications for Biomedical Research. Based on the panel's advice, NIH
developed three key documents to guide its biodefense research program;
these are the NIAID Strategic Plan for Biodefense Research, the NIAID
Research Agenda for Category A Agents (covering agents that pose the
gravest threat to human health, such as those that cause smallpox,
anthrax, botulism, and plague), and the NIAID Research Agenda for
Category B and C Agents (for agents whose biological properties make
them more difficult to deploy or less likely to cause widespread harm
than Category A agents). The strategic plan provided a blueprint to
construct three essential pillars of the biodefense research program:
(1) infrastructure needed to safely conduct research on dangerous
pathogens; (2) basic research on microbes and host immune defenses,
which serves as the foundation for applied research; and (3) targeted,
milestone-driven medical countermeasure development to create the
vaccines, therapeutics, and diagnostics that will be needed in the
event of a bioterror attack. To implement the biodefense agendas,
Congress increased NIH appropriations for biodefense research from $53
million in fiscal year 2001 to $1.5 billion in fiscal year 2003 and
approximately $1.7 billion in fiscal year 2005.
[3] GAO, High-Containment Biosafety Laboratories: Preliminary
Observations on the Oversight of the Proliferation of BSL-3 and BSL-4
Laboratories in the United States, [hyperlink,
http://www.gao.gov/products/GAO-08-108T] (Washington, D.C.: Oct. 4,
2007).
[4] G.K. Gronvall et. al., "Letter to Senator Edward Kennedy and
Senator Richard Burr," Center for Biosecurity, University of Pittsburgh
Medical Center, March 3, 2009.
[5] The request letter contained several questions. In agreement with
our requester, we revised the questions as stated.
[6] Department of Health and Human Services (Washington, D.C., 2007),
Biosafety in Microbiological and Biomedical Laboratories, 5th ed.
[7] Department of Health and Human Services, (Washington, D.C., 2002)
NIH Guidelines for Research Involving Recombinant DNA Molecules.
[8] Variola major virus, by international agreement, can only be worked
on in two specific facilities in the world.
[9] A vivarium is an indoor enclosure for keeping and raising living
animals and plants and observing them under natural conditions.
[10] Some of the federal agencies, such as the Department of Commerce
and the Department of Transportation, help regulate the transport of
hazardous biological agents and toxins that high-containment
laboratories handle.
[11] Select agents are biological agents and toxins (1) that have the
potential to pose a severe threat to public health and safety, to
animal or plant health, or to animal or plant products and (2) whose
possession, use, and transfer are regulated by select agent rules (7
C.F.R. Part 331, 9 C.F.R. Part 121, and 42 C.F.R. Part 73). The CDC and
USDA maintain a list of select agents and toxins.
[12] The LRN was established by the Department of Health and Human
Services, Centers for Disease Control and Prevention (CDC), in
accordance with Presidential Decision Directive 39, which outlined
national antiterrorism policies and assigned specific missions to
federal departments and agencies. Through collaborative efforts
involving LRN founding partners, the FBI, and the Association of Public
Health Laboratories, the LRN became operational in October 1999. Its
objective was to ensure an effective laboratory response to
bioterrorism by helping to improve the nation's public health
laboratory infrastructure. Several years later, the capacity to respond
to chemical terrorism was developed.
[13] Other laws regulate the transfer of various non-select agents that
could originate in or be sent to high-containment laboratories. We do
not discuss these regulations as they are not directly pertinent to
high-containment laboratories.
[14] Pub. L. No. 104-132, 110 Stat. 1214, 1284 (April 24, 1996).
[15] United and Strengthening America by Providing Appropriate Tools
Required to Intercept and Obstruct Terrorism Act of 2001, Pub. L. No.
107-56, 115 Stat. 271, 386 (Oct. 26, 2001).
[16] Pub. L. No. 107-188, 116 Stat. 594, 637-662 (June 12, 2002).
[17] Subtitle B, of title II, of the Bioterrorism Act provides
regulatory authority over select agents and toxins to the Secretary of
Agriculture. This subtitle is cited as the Agricultural Bioterrorism
Protection Act of 2002 (Agricultural Bioterrorism Act).
[18] 61 Fed. Reg. 55190 (Oct. 24, 1996).
[19] 42 C.F.R. Part 73 (CDC); 7 C.F.R. Part 331 (APHIS-plant); 9 C.F.R.
Part 121 (APHIS-animal).
[20] The terms biosafety and biosecurity are sometimes used
interchangeably; however, they are different. In this report, biosafety
refers to practices employed to lower the risk of accidental release of
dangerous pathogens in the laboratory or environmental release from the
laboratory, while biosecurity refers to steps taken to secure pathogens
from theft, unauthorized access, or illegal use.
[21] In the context of the NIH rDNA Guidelines, recombinant DNA
molecules are defined as either (1) molecules that are constructed
outside living cells by joining natural or synthetic DNA segments to
DNA molecules that can replicate in a living cell or (2) molecules that
result from the replication of those described in (1) above.
[22] An entity is defined in the select agent regulations as any
government agency (federal, state, or local), academic institution,
corporation, company, partnership, society, association, firm, sole
proprietorship, or other legal body. A private entity is a company
whose shares are not traded on the open market, as a commercial
entity's are.
[23] A glovebox (or glove box) is a sealed container that is designed
to allow one to manipulate objects while being in a different
atmosphere from the object. Built into the sides of the glovebox are
two gloves arranged in such a way that the user can place his or her
hands into the gloves and perform tasks inside the box without breaking
the seal or allowing potential injury. Part or all of the box is
usually transparent to allow the user to see what is being manipulated.
[24] Although the select agent regulations were not finalized until
2005, interim final rules required registration in 2003.
[25] According to CDC, while this laboratory is being built as a BSL-4
laboratory, it will operate as a BSL-3 laboratory.
[26] The 7 BSL-4 laboratories that are operational as of 2009 and the 7
new facilities that are not yet operational total 14. However, the new
USAMRIID Recapitalization Laboratory will replace an existing facility
at Ft. Detrick, making the total 13. Figure 1, however, includes both
the new and existing USAMRIID facilities since it shows both
operational and nonoperational laboratories as of June 2009.
[27] The response rate for the survey was 41 percent. See appendix I
for additional details.
[28] Entities may define a laboratory as one room or a series of rooms.
[29] Association of Public Health Laboratories, Public Health
Laboratory Issues in Brief: Bioterrorism Capacity (Washington D.C.,
April 2005).
[30] Personal communication from APHL, March 2009.
[31] We reported on the importance of building adequate laboratory
capacity to respond to both natural and terrorist-related outbreaks.
See West Nile Virus Outbreak: Lessons for Public Health Preparedness
([hyperlink, http://www.gao.gov/products/GAO/HEHS-00-180], Sept. 11,
2000) and Infectious Disease Outbreaks: Bioterrorism Preparedness
Efforts Have Improved Public Health Response Capacity, But Gaps Remain
[hyperlink, http://www.gao.gov/products/GAO-03-654T], Apr. 9, 2003.
[32] DSAT officials told us that their current database includes data
on (1) the number of workers approved to have access to select agents
and toxins by CDC or APHIS following a security risk assessment by the
FBI and (2) workers who work with select agents in BSL-2 laboratories.
However, DSAT officials are now working on a system that will be able
to show the number of workers by type of laboratory (for example, BSL-
2, BSL-3, and BSL-4) and type of worker (for example, laboratory staff
and support staff). In accordance with 42 C.F.R. 73.10, security risk
assessments are conducted on all individuals who wish to gain access to
select agents. Following the completion of that assessment, an
individual is granted access approval to select agents provided that
the individual is not identified as a restricted person as defined in
section 175b of title 18 of the United States Code.
[33] Aggregate risks are defined as the sum total of all the risk
elements associated with operating a high-containment laboratory.
[34] HHS has established a Trans-Federal Task Force on Optimizing
Biosafety and Biocontainment Oversight to undertake an intensive
analysis of the current framework of biosafety and biocontainment
oversight of research activities involving infectious agents and toxins
in high-and maximum-containment research facilities with the goal of
exploring strategies to address concerns voiced by Congress and the
general public. The task force is chaired by officials from HHS and
UDSA and comprises representatives from a broad range of federal
departments and agencies that have responsibility for and oversight of
the management of biohazard risks.
[35] Some intelligence agencies have a mission to track and a need to
know the number of all BSL-3 and BSL-4 laboratories or their
equivalents abroad. However, they do not know the total number of those
laboratories.
[36] The current legislation that authorizes work with these high
hazard pathogens is Control of Substances Hazardous to Health (COSHH)
Regulations 2002, Genetically Modified Organisms (Contained Use)
Regulations 2000 (as amended 2005), and Specified Animal Pathogens
Order 2008.
[37] The anthrax attacks came in two waves. The first set of anthrax
letters had a Trenton, New Jersey, postmark dated September 18, 2001,
exactly 1 week after the September 11, 2001, attacks. Three letters are
believed to have been mailed at this time to NBC News and the New York
Post, both located in New York City, and to the National Enquirer at
American Media, Inc., in Boca Raton, Florida. Two more anthrax letters,
bearing the same Trenton postmark, were dated October 9, 3 weeks after
the first mailing. The letters were addressed to two Democratic
Senators, Thomas Daschle of South Dakota and Patrick Leahy of Vermont.
[38] The postal facilities in New Jersey and Washington, D.C., that
processed the senators' letters became heavily contaminated. Other mail
routed through these and other postal facilities also became
contaminated. Numerous federal facilities in the Washington, D.C.,
area--the U.S. Supreme Court and main State Department buildings--were
also found to be contaminated. The mail for these federal facilities
was believed to have either come in direct contact with the
contaminated letters or passed through sorting equipment at the postal
facility that processed the letters. In all, 22 individuals contracted
anthrax disease in four states (Connecticut, Florida, New Jersey, and
New York) and Washington, D.C. Five of the 22 individuals died.
[39] USAMRIID is an Army installation with BSL-3 and BSL-4
laboratories. These laboratories work with select agents and toxins.
USAMRIID is regulated by DOD because it is a military laboratory and by
CDC because it works with select agents and toxins.
[40] Department of the Army, "AR 15-6 Investigation Into Anthrax
Contamination at USAMRIID," May 16, 2002.
[41] Application and Affidavit for Search Warrant Case Number 08-432,
available at [hyperlink,
http://www.fbi.gov/page2/amerithrax-affidavits/07-524-M-01.pdf].
(accessed on June 29, 2009)
[42] While video monitoring addresses the threat of facility misuse to
a certain extent, expert review of the images would be essential to
determine if misuse is occurring.
[43] In 2003, we reported on the risks an insider can pose in a high-
containment laboratory working with animal diseases. See GAO, Combating
Bioterrorism: Actions Needed to Improve Security at Plum Island Animal
Disease Center, GAO-03-847 (Washington, D.C.: Sept. 19, 2003).
[44] Moreover, in reaction to the September 11, 2001, terrorist attack
and the subsequent anthrax incidents, Congress passed several laws (for
example, the USA PATRIOT Act and the Bioterrorism Preparedness and
Response Act of 2002) to combat terrorism and, in doing so,
significantly strengthened the oversight of select agents and increased
safeguards and security requirements.
[45] Report of the National Science Advisory Board for Biosecurity,
Enhancing Personnel Reliability among Individuals with Access to Select
Agents (Washington, D.C.: May 2009).
[46] Memorandum for Chairman, Defense Science Board, "Defense Science
Board Task Force on the Department of Defense Biological Safety and
Security Program," (Washington, D.C, October 3, 2008), p.39.
[47] DOD, Report of the Defense Science Board Task Force, Department of
Defense Biological Safety and Security Program (Washington, D.C., May
2009), p. 39.
[48] Report of the National Science Advisory Board for Biosecurity,
Enhancing Personnel Reliability among Individuals with Access to Select
Agents, May 2009, [hyperlink,
http://oba.od.nih.gov/biosecurity/nsabb_past_meetings.html] (accessed
August 5, 2009).
[49] Executive Order 13486, January 9, 2009, "Strengthening Laboratory
Biosecurity in the United States."
[50] Microorganism populations are constantly in a state of flux where
fractions of the total may be multiplying or dying off. This dynamic
situation, coupled with the extraordinarily high numbers of organisms
(billions per milliliter) and the inherent inaccuracies of assay
methods, make it unrealistic to assign conclusive numbers to microbial
populations in storage and working stocks.
[51] The CDC inspected laboratories at TAMU on February 22, 2006, and
documented 47 facility "departures" but did not note any of the
violations later uncovered.
[52] The Sunshine Project, Mandate for Failure, The State of
Institutional Biosafety Committees in an Age of Biological Weapons
Research (Austin, Texas, Oct. 4, 2004).
[53] According to the CDC, even though the worker was escorted, having
her help out with the aerosolization chamber during the Brucella
experiments constituted unauthorized access to a select agent (since
she was not authorized to work with Brucella) and violated regulations.
[54] Although TAMU did not notify DSAT that it was conducting
aerosolization work with Brucella, TAMU still had the responsibility to
train the staff.
[55] Although a person typically has to breathe in M. tuberculosis
bacteria to get an infection, Brucella can enter the system through
mucous membranes, such as those in the eyes. During the experiment, the
lab worker who was exposed had been wearing a respirator that filtered
the air she breathed, as is recommended for work with M. tuberculosis.
[56] ID50 is the dose needed to infect 50 percent of exposed
individuals.
[57] On July 13, 2009, DSAT published a notice in the Federal Register
proposing the addition of SARS-associated coronavirus (SARS-CoV) to the
list of select agents. The Federal Register notice can be found at
[hyperlink, http://edocket.access.gpo.gov/2009/pdf/E9-16536.pdf].
[58] See [hyperlink, www.selectagents.gov/resources/CDC-
APHIS_Theft_loss_Release_Information_Document.pdf].
[59] For additional information, see E.J. Baron and J. M. Miller,
"Bacterial and Fungal Infections Among Diagnostic Laboratory Workers:
Evaluating the Risks," Diagnostic Microbiology and Infectious Diseases,
epub; D.L Sewell, "Laboratory-Associated Infections and Biosafety,"
Clinical Microbiology Reviews, Vol. 8, No. 3 (1995); R.M. Pike et al.,
"Continuing Importance of Laboratory Acquired Infections," American
Journal of Public Health, Vol. 55, No. 2 (February 1965).
[60] High-Containment Biodefense Research Laboratories, Meeting Report
and Center Recommendations, Biosecurity and Bioterrorism, vol. 5, 1
(New Rochelle, N.Y., March 2007).
[61] Department of Transportation, Federal Aviation Administration, FAA
Procedures for Handling National Transportation Safety Board
Recommendations (Washington, D.C., Federal Aviation Administration,
March 22, 1995). Also see Federal Aviation Administration, Accident and
Incident Data (Washington, D.C., Sept. 29, 2006).
[62] According to DSAT, their "concern was not necessarily with TAMU's
interpretation of the titers, but rather, that TAMU lacked an effective
surveillance system. An elevated titer may result in the conclusion
that the person was exposed to the agent. However, the entity must
perform a follow-up investigation to determine if the elevated titer is
the result of: (1) previous exposure to the organism prior to work at
the entity; (2) possible exposure to the organism while doing non-work-
related activities; or exposure at the workplace."
[63] This document is available on the National Select Agent Registry
Web site: [hyperlink, http://www.selectagents.gov/resources/CDC-
APHIS_Theft_Loss_Release_Information_Document.pdf].
[64] 42 U.S.C. § 262a(i) (Bioterrorism Act); 42 C.F.R. § 73.21.
[65] For ease of reading, we have chosen not to include technically
detailed descriptions of CDC's primary and backup power systems. For
further information concerning the general requirements of backup
power, please see (1) National Fire Protection Association, NFPA 70,
National Electric Code 2008 Edition (Quincy, MA) (a) "Article 700
Emergency Systems;" (b) "Article 701 Legally Required Standby Systems;"
and (c) "Article 702 Optional Standby Systems" and (2) National Fire
Protection Association, NFPA 110, Standard for Emergency and Standby
Power Systems 2005 Edition (Quincy, MA).
[66] In commenting on our draft report, CDC stated that lapses in
electrical power are highly likely regardless of the cause and type of
laboratory or facility being served. CDC, as a result, employs an
integrated approach combining laboratory procedures/training, health
and safety protocols, and engineering/facility controls. CDC stated
that the BMBL treats engineering controls for high-containment
laboratories as secondary containment.
[67] In commenting on our draft report, CDC stated that "as a
consequence of the lightning strike, building 18 immediately
experienced a blackout except for areas served from the uninterruptible
power system (UPS) for the building. CDC operational staff immediately
responded to the loss of power by following operational protocols that
require the operator to investigate the possible cause of power loss
and resetting over-current devices, if necessary, to restore normal or
backup power, if required, to the building. After performing a brief
survey of building systems and areas, CDC operational staff proceeded
to the electrical switchgear room located on the triple sub-basement of
building 18. CDC operational staff noticed that both 480 main breakers
for the building were in a tripped status. The operator attempted to
manually reset both tripped main breakers without success, whereupon
the operator determined both breakers were restricted-open per system
safety interlock. Upon further analyses and review, CDC determined that
both main breakers tripped on ground fault current in excess of set
limits. After a thorough review of the electrical system, the main
breakers were reset and power was restored at the building in
approximately 1 hour."
[68] The laboratory's negative air pressure system is fan-operated and
is designed to prevent potentially contaminated air from leaving the
lab without first being treated to neutralize the contamination.
[69] A subsequent third-party investigation determined that the
grounding of another building housing CDC's older BSL-4 laboratories
was also compromised in a similar fashion.
[70] In commenting on the draft report, CDC stated that while
directional airflow and negative pressure in BSL-4 laboratories are
crucial engineering components of a normal "safe" operating
environment, engineering systems do fail from time to time for various
reasons. Therefore, CDC relies on a "three-legged" approach to
biocontainment (combining laboratory procedures/training, health and
safety protocols, and engineering controls) to ensure that material is
not released outside. Details on CDC's approach are included in
appendix VI. We agree that the three-legged approach offers multiple
layers of containment; however, CDC does not address the point we are
making about the weaknesses we have identified in its electrical
system.
[71] Power failures can also occur intentionally. We reported in 2003
on suspicious power failures at a high-containment laboratory working
with foreign animal diseases. See GAO-03-847, 20-21.
[72] On May 27-30, 2008, DSAT inspected this laboratory, which included
a review of the incident response plan in the event of a power outage.
On October 8, 2008, DSAT approved this laboratory for registration.
[73] See Department for Environment, Food, and Rural Affairs, Foot and
Mouth Disease: Applying the Lessons (London, U.K., National Audit
Office, Feb. 2, 2005). We also reported on this 2001 U.K. incident. See
GAO, Foot and Mouth Disease: To Protect U.S. Livestock, USDA Must
Remain Vigilant and Resolve Outstanding Issues, [hyperlink,
http://www.gao.gov/products/GAO-02-808] (Washington, D.C.: July 26,
2002).
[74] In commenting on our draft report, NIAID noted that the
cooperative awards were made to the NBLs in fiscal year 2006 to
"develop and maintain the research resources and facilities needed to
meet national, regional, and local biodefense and emerging infectious
diseases research needs." NIAID plans to continue support for these
awards.
[75] Reconstructed replication competent forms of the 1918 pandemic
influenza virus containing any portion of the coding regions of all
eight gene segments.
[76] A virulent Newcastle disease virus (avian paramyxovirus serotype
1) has an intracerebral pathogenicity index in day-old chicks (Gallus
gallus) of 0.7 or greater or has an amino acid sequence at the fusion
(F) protein cleavage site that is consistent with virulent strains of
Newcastle disease virus. A failure to detect a cleavage site that is
consistent with virulent strains does not confirm the absence of a
virulent virus.
[77] In 2007, Army regulation 385-10, the Army Safety Program, provided
policies on safety that included biological safety.
[End of section]
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