GAO 

United States Government Accountability Office

Report to Congressional Requesters

HIGH-CONTAINMENT 

LABORATORIES 

National Strategy for 

Oversight Is Needed 

September 2009 

GAO-09-574 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

September 2009

HIGH-CONTAINMENT LABORATORIES

National Strategy for Oversight Is Needed 

Highlights of GAO-09-574, a report to 

congressional requesters 

U.S. laboratories working with 

dangerous biological pathogens 

(commonly referred to as highcontainment 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 Recommends

GAO is recommending that (1) the 

National Security Advisor name an 

entity charged with governmentwide strategic evaluation of highcontainment 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. 

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 highcontainment 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 highcontainment 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. 

View GAO-09-574 or key components. 

For more information, contact Nancy 

Kingsbury at (202) 512-2700 or 

kingsburyn@gao.gov. 
Page i GAO-09-574 

Contents 

Letter 1

Background 3 

The Number of BSL-4 and BSL-3 Laboratories and Their Workforce 

Is Increasing in Different Sectors throughout the United States 19 

No Federal Agency Has the Mission to Track the Expansion of All 

High-Containment Laboratories and Regulate Biosafety in the 

United States 32 

Lessons Learned from Four Incidents Highlight the Risks Inherent 

in the Expansion of High-Containment Laboratories 36 

Conclusions 66 

Recommendations for Executive Action 68 

Agency Comments and Our Evaluations 69 

Appendix I Scope and Methodology 73 

Appendix II Expert Panel 75 

Appendix III List of Select Agents and Toxins as of 

November 17, 2008 76 

Appendix IV Biological Agents Recommended for BSL-3 

Containment That Are Not Select Agents 79 

Appendix V The Army’s Requirements for High-Containment 

Laboratories in 2001 80 

Appendix VI CDC’s Integrated Approach to Biocontainment at 

High-Containment Laboratories 82 

High-Containment Laboratories 
Appendix VII Comments from the Department of Health and 

Human Services 84 

Appendix VIII Comments from the Department of Agriculture 92 

Appendix IX GAO Contact and Staff Acknowledgments 96 

Related GAO Products 97 

Tables 

Table 1: Recommended Biosafety Levels for Laboratories Working 

with Human Pathogens 5 

Table 2: Recommended Biosafety Levels for Activities in Which 

Experimentally or Naturally Infected Vertebrate Animals 

Are Used 7 

Table 3: Entities Registered with DSAT That Maintain BSL-4 

Laboratories, by Calendar Year and Sector 21 

Table 4: BSL-3 Laboratories Maintained by Entities Registered with 

DSAT, by Calendar Year and Sector 25 

Table 5: BSL-3 Laboratories Maintained by Entities Registered with 

APHIS, by Calendar Year and Sector 26 

Table 6: BSL-3 Laboratories in the State Public Health System 27 

Table 7: Individuals with Active Access Approvals from DSAT and 

APHIS, by End of Calendar Year and Sector 29 

Table 8: DSAT Budget and Staff for Select Agent Oversight 

Program by Fiscal Year 30 

Table 9: APHIS’s Budget and Staff for Select Agent Oversight 

Program 31 

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 32 

Table 11: Agents Requiring BSL-2 Containment, Rarely BSL-3 

Containment 79 

Table 12: Agents Typically Requiring BSL-3 Containment 79 

Page ii GAO-09-574 High-Containment Laboratories
Figures 

Figure 1: Entities Registered with DSAT That Maintain BSL-4 

Laboratories, by Calendar Year and Sector 23 

Figure 2: BSL-3 Laboratories Maintained by Entities Registered 

with DSAT, by Calendar Year and Sector 25 

Figure 3: BSL-3 Laboratories Maintained by Entities Registered 

with APHIS, by Calendar Year and Sector 28 

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 

Page iii GAO-09-574 High-Containment Laboratories
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 

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Page iv GAO-09-574 High-Containment Laboratories
Page 1 GAO-09-574 

 

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.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.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. 

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 highcontainment 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, milestonedriven 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. 

High-Containment Laboratories 
 

In 2007, we reported on issues associated with the proliferation of highcontainment laboratories in the United States, including risks posed by 

biosafety incidents that have occurred in the past.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.4

 In this context, you asked us to address the following 

questions:5

1. To what extent, and in what areas, has the number of highcontainment laboratories increased in the United States? 

2. Which federal agency is responsible for tracking the expansion of highcontainment laboratories and determining the associated aggregate 

risks? 

3. What lessons can be learned from highly publicized incidents at highcontainment 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 

 

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, 

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. 

Page 2 GAO-09-574 High-Containment Laboratories
 

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 HighContainment 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 

Page 3 GAO-09-574 High-Containment Laboratories
 

developed and provided biosafety guidelines outlined in the manual titled 

Biosafety in Microbiological and Biomedical Laboratories (BMBL).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) 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. 

 

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. 

Page 4 GAO-09-574 High-Containment Laboratories
 

Table 1: Recommended Biosafety Levels for Laboratories Working with Human Pathogens 

Biosafety 

level Agent Practices 

Primary barriers and 

safety equipment 

Facilities (secondary 

barriers) 

1 Not known to consistently 

cause diseases in healthy 

adults 

Standard microbiological 

practices 

None required Laboratory bench and sink 

required 

2 • Agents associated with 

human disease 

• Routes of transmission 

include percutaneous 

injury, ingestion, and 

mucous membrane 

exposure 

BSL-1 practice plus 

• limited access 

• biohazard warning 

signs 

• “sharps” precaution 

• biosafety manual 

defining any needed 

waste decontamination 

or medical surveillance 

policies 

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 

BSL-1 plus 

• autoclavea available 

3 • Indigenous or exotic 

agents with potential 

for aerosol 

transmission 

BSL-2 practice plus 

• controlled access 

• decontamination of all 

waste 

• decontamination of 

laboratory clothing 

before laundering 

• baseline serum 

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 

BSL-2 plus 

• physical separation 

from access corridors 

• self-closing, doubledoor access 

• exhaust air not 

recirculated 

• negative airflow into 

laboratory 

4 • 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 

BSL-3 practices plus 

• clothing change before 

entering 

• shower on exit 

• all material 

decontaminated on exit 

from facility 

Primary barriers: 

• all procedures 

conducted in class III 

BSCs or class I or II 

BSCs in combination 

with full-body, airsupplied positive 

pressure personnel unit 

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. 

Page 5 GAO-09-574 High-Containment Laboratories
 

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.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. 

 

8

Variola major virus, by international agreement, can only be worked on in two specific 

facilities in the world. 

Page 6 GAO-09-574 High-Containment Laboratories
 

Table 2: Recommended Biosafety Levels for Activities in Which Experimentally or Naturally Infected Vertebrate Animals Are 

Used 

ABSL Agents Practices 

Primary barriers and safety 

equipment 

Facilities (secondary 

barriers) 

1 Not known to consistently 

cause diseases in healthy 

adults 

Standard animal care and 

management practices, 

including appropriate medical 

surveillance programs 

As required for normal care of 

each species 

Standard animal facility: 

• no recirculation of 

exhaust air 

• directional air flow 

recommended 

• hand washing sink is 

available 

2 • Associated with human 

disease 

• Hazard: percutaneous 

exposure, ingestion, or 

mucous membrane 

exposure. 

ABSL-1 practice plus: 

• limited access 

• biohazard warning signs 

• “sharps” precautions 

• biosafety manual 

• decontamination of all 

infectious wastes and 

animal cages prior to 

washing 

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 

ABSL-1 plus: 

• autoclave available 

• hand washing sink 

available 

• mechanical cage washer 

recommended 

3 • Indigenous or exotic 

agents with potential for 

aerosol transmission 

• Disease may have 

serious health effects 

ABSL-2 practice plus: 

• controlled access 

• decontamination of 

clothing before 

laundering 

• cages decontaminated 

before bedding removed 

• disinfectant foot bath as 

needed 

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 

ABSL-2 facility plus: 

• physical separation from 

access corridors 

• self-closing, double-door 

access 

• sealed penetrations 

• sealed windows 

• autoclave available in 

facility 

4 • Dangerous/exotic agents 

that pose high risk of lifethreatening disease 

• Aerosol transmission or 

related agents with 

unknown risk of 

transmission 

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 

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 

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. 

Page 7 GAO-09-574 High-Containment Laboratories
 

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.9

Agricultural Biosafety 

Levels 

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 HighContainment 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.10 Examples include the following: 

 

9

A vivarium is an indoor enclosure for keeping and raising living animals and plants and 

observing them under natural conditions. 

10Some 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. 

Page 8 GAO-09-574 High-Containment Laboratories
 

• The Centers for Disease Control and Prevention (CDC) has its own highcontainment 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.11 CDC also funds some 

laboratory activities carried out in state public health laboratories, 

commonly referred to as the Laboratory Response Network (LRN).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. 

 

11Select 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. 

12The 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 capcaity to respond to chemical terrorism was developed. 

Page 9 GAO-09-574 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, contractoroperated 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 highcontainment laboratories and funds a variety of research requiring highcontainment 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 

Page 10 GAO-09-574 High-Containment Laboratories
 

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.13 The following is a short summary of pertinent laws, regulations, 

and guidance. 

Following the Oklahoma City bombing in 1995, Congress passed the 

Antiterrorism and Effective Death Penalty Act of 1996 to deter terrorism, 

among other reasons.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. 

Pertinent Laws 

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 Act15 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 

 

13Other 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. 

14Pub. L. No. 104-132, 110 Stat. 1214, 1284 (April 24, 1996). 

15United 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). 

Page 11 GAO-09-574 High-Containment Laboratories
 

Security and Bioterrorism Preparedness and Response Act of 2002 

(Bioterrorism Act),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;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); 

 

16Pub. L. No. 107-188, 116 Stat. 594, 637-662 (June 12, 2002). 

17Subtitle 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). 

Page 12 GAO-09-574 High-Containment Laboratories
 

• 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 Select Agent Program Regulations 

Guidance 

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.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 

 

1861 Fed. Reg. 55190 (Oct. 24, 1996). 

Page 13 GAO-09-574 High-Containment Laboratories
 

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, 2005.19 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; 

 

1942 C.F.R. Part 73 (CDC); 7 C.F.R. Part 331 (APHIS-plant); 9 C.F.R. Part 121 (APHISanimal). 

Page 14 GAO-09-574 High-Containment Laboratories
 

• 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,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. 

 

20The 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. 

Page 15 GAO-09-574 High-Containment Laboratories
 

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 

www.selectagents.gov. The BMBL has become the code of practice for 

laboratory principles, practices, and procedures. 

Page 16 GAO-09-574 High-Containment Laboratories
 

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: 

http://oig.hhs.gov/fraud/enforcement/cmp/agents_toxins.asp and 

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. 

Page 17 GAO-09-574 High-Containment Laboratories
 

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 

Page 18 GAO-09-574 High-Containment Laboratories
 

research involving rDNA are set by the NIH Guidelines for Research 

Involving Recombinant DNA Molecules (NIH rDNA Guidelines).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. 

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 

The Number of BSL-4 

and BSL-3 

Laboratories and 

Their Workforce Are 

Increasing in 

Different Sectors 

throughout the United 

States 

 

21In 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. 

Page 19 GAO-09-574 High-Containment Laboratories
 

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 BSL4 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 entities22 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 

 

22An 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. 

Page 20 GAO-09-574 High-Containment Laboratories
 

laboratory (a glovebox, rather than a conventional laboratory)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.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 

Number of BSL-4 laboratories by sector 

Year 

Total number 

of entities 

Federal 

government 

State/local 

government Academic

Private 

(nonprofit) 

Commercial

(for profit)

2004 5 2 0 2 1 0

2005 5 2 0 2 1 0

2006 5 2 0 2 1 0

2007 5 2 0 2 1 0

2008 5 2 0 2 1 0

2009 7 4 0 2 1 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. 

Since the anthrax attacks in 2001, seven new BSL-4 facilities are in the 

planning, construction, or commissioning stage. Four of these facilities are 

 

23A 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. 

24Although the select agent regulations were not finalized until 2005, interim final rules 

required registration in 2003. 

Page 21 GAO-09-574 High-Containment Laboratories
 

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.25

The total number of BSL-4 laboratorieswill increase from 7 to 13 when 

these laboratories become operational. 26 The locations of the BSL-4 

 

25According to CDC, while this laboratory is being built as a BSL-4 laboratory, it will 

operate as a BSL-3 laboratory. 

26The 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. 

Page 22 GAO-09-574 High-Containment Laboratories
 

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 

Southwest Foundation for 

Biomedical Research

San Antonio, TX

NIAID Rocky Mountain Lab

Hamilton, MT

NIAID Integrated Research Facility

Fort Detrick, MD

Virginia Division of Consolidated 

Laboratory Services

Richmond, VA

Boston University NBL

Boston, MA

DOD USAMRIID 

Fort Detrick, MD

DHS National Bio and 

Agro-Defense Facility (NBAF)

Manhattan, KS 

Source: GAO design based on NIAID information. Art Explosion (map), open sources.

Foundation for

Research

TX

MT

Virg

Lab

Rich

Boston University NBL

Boston, MA

Manhattan, KS

DHS National Biodefense Analysis 

and Countermeasures Center

Fort Detrick, MD

Operational

Not Operational

 BIOHAZARD WASTE

Georgia State University

Atlanta, GA

 BIOHAZARD WASTE BIOHAZARD WASTE BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

CDC

Atlanta, GA

University of Texas Medical Branch 

Galveston, TX

 BIOHAZARD WASTE

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. 

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. 

Page 23 GAO-09-574 High-Containment Laboratories
 

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. 

BSL-3 Laboratories Are 

Being Built in All Sectors 

throughout the United 

States 

In April 2007, we conducted a Web-based survey—based on a search of 

publicly available sources—of contacts knowledgeable about highcontainment laboratories (for example, biosafety officers).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).28

 

27The response rate for the survey was 41 percent. See appendix I for additional details. 

28Entities may define a laboratory as one room or a series of rooms. 

Page 24 GAO-09-574 High-Containment Laboratories
 

Figure 2: BSL-3 Laboratories Maintained by Entities Registered with DSAT, by 

Calendar Year and Sector 

Laboratories

Entities

0

200

400

600

800

1,000

1,200

1,400

1,600

2004 2005 2006 2007 2008

Number

Source: GAO analysis based on NIAID information.

Year

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 

Sector 

Year 

Number of 

entities 

Number of 

laboratories 

Federal 

government

State/local 

government Academic 

Private

(nonprofit)

Commercial

(for profit)

2004 150 415 130 118 120 28 19

2005 210 782 192 171 299 76 44

2006 237 1,086 271 220 438 95 62

2007 238 1,176 347 254 388 119 68

2008 242 1,362 395 295 474 125 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). 

Page 25 GAO-09-574 High-Containment Laboratories
 

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 

Sector 

Year 

Number of 

entities 

Number of 

laboratories 

Federal 

government

State/local 

government Academic 

Private

(nonprofit)

Commercial

(for profit)

2004 41 290 179 10 42 20 39

2005 42 293 179 10 48 20 36

2006 44 299 179 15 49 20 36

2007 45 303 179 15 48 20 41

2008 37a 281 179 8 45 20 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. 

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.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.30

 

29Association of Public Health Laboratories, Public Health Laboratory Issues in Brief: 

Bioterrorism Capacity (Washington D.C., April 2005). 

30Personal communication from APHL, March 2009. 

Page 26 GAO-09-574 High-Containment Laboratories
 

Table 6: BSL-3 Laboratories in the State Public Health System 

Calendar year State public health BSL-3 laboratories

2001 69

2002 71

2003 139

Source: Association of Public Health laboratories, 2005. 

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.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. 

 

31We 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 (GAO/HEHS-00-180, Sept. 11, 2000) and Infectious Disease 

Outbreaks: Bioterrorism Preparedness Efforts Have Improved Public Health Response 

Capacity, But Gaps Remain (GAO-03-654T, Apr. 9, 2003). 

Page 27 GAO-09-574 High-Containment Laboratories
 

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 

University of Hawaii at Manoa 

Honolulu, HI

University of Louisville 

Louisville, KY

Tufts University School of 

Veterinary Medicine 

Grafton, MA

University of Medicine and 

Dentistry of New Jersey 

Newark, NJ

University of Pittsburgh 

Pittsburgh, PA

University of Alabama-Birmingham 

School of Medicine 

Birmingham, AL

University of Chicago 

Argonne, IL

George Mason University 

Fairfax, VA

University of Tennessee 

Memphis, Tennessee

Tulane National Primate Research Center 

Covington, LA

University of Missouri, Columbia 

College of Veterinary Medicine 

Columbia, MO

Operational

Not Operational

 BIOHAZARD WASTE

Source: GAO design based on NIAID information. Art Explosion (map).

Duke University Medical Center 

Durham, NC

oa 

University of Lo

Louisville, KY

Vet

Gra

Univ

Pitts

University of Alabama-B

University of Chicago

Argonne, IL

Georg

Fairfa

Columbia, MO

Duke Univers

Durham, NC

 BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

 BIOHAZARD WASTE

Colorado State University 

Fort Collins, CO

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. 

Page 28 GAO-09-574 High-Containment Laboratories
 

Table 7: Individuals with Active Access Approvals from DSAT and APHIS, by End of Calendar Year and Sector 

Sector 

Year 

Number of 

individualsa

Federal 

government

State/local 

government Academic

Private 

(nonprofit)

Commercial

(for-profit)

2004 8,335 2,629 1,986 2,309 784 627

2005 9,603 2,776 2,280 2,760 982 805

2006 10,134 2,912 2,420 3,006 975 821

2007 10,473 3,067 2,517 3,090 1,004 795

2008 10,365 3,006 2,384 3,110 1,036 829

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. 

In 2004, 8,335 individuals had access approvals. This number increased to 

10,365 by 2008.32 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. 

 

32DSAT 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. 

Page 29 GAO-09-574 High-Containment Laboratories
 

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. 

Budget and Resources for 

Select Agent Oversight 

Program 

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 

Total DSAT staff DSAT inspectors 

Fiscal 

year 

DSAT budget (current 

dollars in millions)a

Federal staffb

Contract staffcFederal inspectors Contract inspectors

2004 $14.2 18 58 5 20

2005 $13.5 17 63 6 23

2006 $13.0 16 64 9 22

2007 $14.3 18 60 10 17

2008 $12.1 22 64 11 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. 

Page 30 GAO-09-574 High-Containment Laboratories
 

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. 

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 

APHIS Staff 

Fiscal year 

APHIS budget (current 

dollars in millionsa

) Federal staffb Contract staff

Federal inspectors 

(staff years)c

Contract 

inspectors

2004 - - 0 3 0

2005 $2.5 6 0 4 0

2006 $3.5 18 0 5 0

2007 $3.5 18 0 5 0

2008 $4.2 18 0 5 0

2009 $5.2 22 0 5 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. 

Page 31 GAO-09-574 High-Containment Laboratories
 

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.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. 

No Federal Agency 

Has the Mission to 

Track the Expansion 

of All HighContainment 

Laboratories and 

Regulate Biosafety in 

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 Mission to track Know the number 

Department of Commerce No No 

Department of Defense No No 

Department of Energy No No 

Department of Health and Human Services No No 

Department of Homeland Security No No 

Department of Interior No No 

Department of Justice No No 

Department of Labor No No 

Department of State No No 

Department of Veterans Affairs No No 

Environmental Protection Agency No No 

U.S. Department of Agriculture No No 

Source: GAO Survey of Federal Agencies Involved with BSL-3 and BSL-4 laboratories, 2007. 

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. 

 

33Aggregate risks are defined as the sum total of all the risk elements associated with 

operating a high-containment laboratory. 

Page 32 GAO-09-574 High-Containment Laboratories
 

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.34

Risks Associated with the 

Expansion of HighContainment 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.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 

 

34HHS 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. 

35Some 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. 

Page 33 GAO-09-574 High-Containment Laboratories
 

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 HighContainment Laboratories 

Currently, no laws in the United States specifically focus on all highcontainment 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. 

Page 34 GAO-09-574 High-Containment Laboratories
 

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 highcontainment 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.36

 

36The 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. 

Page 35 GAO-09-574 High-Containment Laboratories
 

Lessons Learned from 

Four Incidents 

Highlight the Risks 

Inherent in the 

Expansion of HighContainment 

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 footand-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.37 The 

 

37The 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. 

Page 36 GAO-09-574 High-Containment Laboratories
 

letters led to the first U.S. cases of anthrax disease related to bioterrorism, 

and the subsequent investigation by FBI has been called “Amerithrax.”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.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 

 

38The 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. 

39USAMRIID 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. 

Page 37 GAO-09-574 High-Containment Laboratories
 

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 investigation40 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 

 

40Department of the Army, “AR 15-6 Investigation Into Anthrax Contamination at 

USAMRIID,” May 16, 2002. 

Page 38 GAO-09-574 High-Containment Laboratories
 

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.’”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 

 

41Application and Affidavit for Search Warrant Case Number 08-432, available at 

www.fbi.gov/page2/amerithrax-affidavits/07-524-M-01.pdf. (accessed on June 29, 2009)

Page 39 GAO-09-574 High-Containment Laboratories
 

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. 

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. 

Lessons Learned: Insider Risk 

and Inventory Control of 

Biological Agents 

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 

Page 40 GAO-09-574 High-Containment Laboratories
 

address insider threats, we are not aware of any evaluation of the 

effectiveness of these measures.42 While there are clearly major difficulties 

in imposing such controls in research laboratories, insider risk needs to be 

recognized and evaluated.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.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.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 reliabilit

program is unnecessary at 

y 

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 

42While 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. 

43In 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). 

44Moreover, 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. 

45Report of the National Science Advisory Board for Biosecurity, Enhancing Personnel 

Reliability among Individuals with Access to Select Agents (Washington, D.C.: May 2009). 

Page 41 GAO-09-574 High-Containment Laboratories
 

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 

Page 42 GAO-09-574 High-Containment Laboratories
 

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 Security46 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.”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 

 

46Memorandum 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. 

47DOD, Report of the Defense Science Board Task Force, Department of Defense 

Biological Safety and Security Program (Washington, D.C., May 2009), p. 39. 

Page 43 GAO-09-574 High-Containment Laboratories
 

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.” 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.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.” 

 

48Report of the National Science Advisory Board for Biosecurity, Enhancing Personnel 

Reliability among Individuals with Access to Select Agents, May 2009, 

http://oba.od.nih.gov/biosecurity/nsabb_past_meetings.html (accessed August 5, 2009). 

49Executive Order 13486, January 9, 2009, “Strengthening Laboratory Biosecurity in the 

United States.” 

Page 44 GAO-09-574 High-Containment Laboratories
 

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. 

Page 45 GAO-09-574 High-Containment Laboratories
 

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.50

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. 

Actions Taken by the 

Regulatory Agency—DSAT—

Subsequent to the Incident 

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. 

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 

Barriers to Reporting 

Laboratory Accidents 

 

50Microorganism 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. 

Page 46 GAO-09-574 High-Containment Laboratories
 

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.51 Symptoms did not start to appear in the exposed worker until 

more than a month after the exposure, and then the symptoms were flulike. 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 documentation52 acquired through 

Texas’s freedom of information law, uncovered the lapse in reporting. This 

prompted TAMU to notify DSAT. 

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.53 According to DSAT, TAMU failed to report to 

DSAT that it was conducting aerosolization work with Brucella. Therefore, 

Training of Laboratory

Personnel 

 

51The CDC inspected laboratories at TAMU on February 22, 2006, and documented 47 

facility “departures” but did not note any of the violations later uncovered. 

52The Sunshine Project, Mandate for Failure, The State of Institutional Biosafety 

Committees in an Age of Biological Weapons Research (Austin, Texas, Oct. 4, 2004). 

53According 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. 

Page 47 GAO-09-574 High-Containment Laboratories
 

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.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.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).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. 

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 

Medical Provider Lacked 

Information to Diagnose 

Possible Infection Quickly 

 

54Although TAMU did not notify DSAT that it was conducting aerosolization work with 

Brucella, TAMU still had the responsibility to train the staff. 

55Although 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. 

56ID50 is the dose needed to infect 50 percent of exposed individuals. 

Page 48 GAO-09-574 High-Containment Laboratories
 

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.57

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 

Confusion over the Definition 

of Exposure 

 

57On 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 http://edocket.access.gpo.gov/2009/pdf/E9-16536.pdf

Page 49 GAO-09-574 High-Containment Laboratories
 

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 onehalf 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. 

Page 50 GAO-09-574 High-Containment Laboratories
 

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.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. 

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. 

Lessons Learned: Barriers to 

Reporting, Compliance with 

Regulations Regarding 

Training, Informing Medical 

Providers, and Defining 

Exposure 

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 

 

58See www.selectagents.gov/resources/CDCAPHIS_Theft_loss_Release_Information_Document.pdf. 

Page 51 GAO-09-574 High-Containment Laboratories
 

combination thereof.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 laboratoryacquired 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.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. 

 

59For 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). 

60High-Containment Biodefense Research Laboratories, Meeting Report and Center 

Recommendations, Biosecurity and Bioterrorism, vol. 5, 1 (New Rochelle, N.Y., March 

2007). 

Page 52 GAO-09-574 High-Containment Laboratories
 

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.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. Nonlaboratory 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 

 

61Department 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). 

Page 53 GAO-09-574 High-Containment Laboratories
 

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 

Page 54 GAO-09-574 High-Containment Laboratories
 

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.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. 

 

62According 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.” 

Page 55 GAO-09-574 High-Containment Laboratories
 

To help clarify any confusion about what is considered a reportable theft, 

loss, or release, CDC released a new guidance document.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 serologybased 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 

 

63This document is available on the National Select Agent Registry Web site: 

http://www.selectagents.gov/resources/CDC-APHIS_Theft_Loss_Release_Information_Doc

ument.pdf

Page 56 GAO-09-574 High-Containment Laboratories
 

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. 

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. 

Actions Taken by the 

Regulatory Agency—DSAT—

Subsequent to the Incident 

Page 57 GAO-09-574 High-Containment Laboratories
 

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.64 The HHS OIG 

and TAMU disagreed on the number of violations. In February 2008, TAM

agreed to pay a $1 million fine, which was an unprecedented amount for a 

fine paid by any institution under the select agent program. 

U 

 

Incident 3: Power Failures 

at CDC’s HighContainment Laboratories 

Continuity of electrical power is vital for the safe functioning of highcontainment laboratories, in particular since maintenance of essential 

pressure differentials using electrically driven fans provides an important 

barrier for preventing the uncontrolled release of agents.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.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 

6442 U.S.C. § 262a(i) (Bioterrorism Act); 42 C.F.R. § 73.21. 

65For 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). 

66In 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. 

Page 58 GAO-09-574 High-Containment Laboratories
 

generator plant were unavailable.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.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.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 

 

67In 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.” 

68The 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. 

69A 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. 

Page 59 GAO-09-574 High-Containment Laboratories
 

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 

Page 60 GAO-09-574 High-Containment Laboratories
 

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.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.71

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 

Lessons Learned: BSL -3 and -4 

Laboratory Safety Measures 

Must Be Commensurate with 

the Level of Risk These 

Laboratories Present 

 

70In 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. 

71Power 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. 

Page 61 GAO-09-574 High-Containment Laboratories
 

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 highcontainment 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. 

Page 62 GAO-09-574 High-Containment Laboratories
 

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.72

Actions Taken by the 

Regulatory Agency—DSAT—

Subsequent to the Incident 

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 highcontainment 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.73 Therefore, U.K. 

government officials worked quickly to contain and investigate this recent 

incident. 

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. 

Lesson Learned: Facilities 

Supporting High-Containment 

Laboratories Must Ensure the 

Operational Effectiveness of 

Physical Infrastructure 

 

72On 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. 

73See 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, GAO-02-808 (Washington, 

D.C.: July 26, 2002). 

Page 63 GAO-09-574 High-Containment Laboratories
 

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.74

The Pirbright incident shows that beyond initial design and construction, 

ongoing maintenance plays a critical role in ensuring that highcontainment 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. 

 

74In 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. 

Page 64 GAO-09-574 High-Containment Laboratories
 

Since the outbreak of foot-and-mouth disease originating from Pirbright, a 

number of regulatory decisions have been made: 

Actions Taken by the U.K. 

Regulatory Agency Subsequent 

to the Incident 

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. 

Page 65 GAO-09-574 High-Containment Laboratories
 

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. 

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. 

Conclusions 

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. 

Page 66 GAO-09-574 High-Containment Laboratories
 

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 

Page 67 GAO-09-574 High-Containment Laboratories
 

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. 

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 

Recommendations for 

Executive Action 

(1) determine 

• the number, location, and mission of the laboratories needed to effectively 

meet national goals to counter biothreats; 

Page 68 GAO-09-574 High-Containment Laboratories
 

• 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 longterm 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. 

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. 

Agency Comments 

and Our Evaluations 

Page 69 GAO-09-574 High-Containment Laboratories
 

Page 70 GAO-09-574 High-Containment Laboratories 

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 

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. 

Nancy Kingsbury, Ph.D. 

Managing Director, Applied Research 

 and Methods 
 

Page 71 GAO-09-574 High-Containment Laboratories 

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 
 

Page 72 GAO-09-574 High-Containment Laboratories 

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 
Appendix I: Scope and Methodology 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 

Page 73 GAO-09-574 High-Containment Laboratories 
Appendix I: Scope and Methodology 

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. 

Page 74 GAO-09-574 High-Containment Laboratories
Appendix II: Expert Panel 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. 

Page 75 GAO-09-574 High-Containment Laboratories 
Appendix III: List of Select Agents and Toxins Appendix III: List of Select Agents and Toxins as of November 17, 2008 

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 1

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 

 

1

 Reconstructed replication competent forms of the 1918 pandemic influenza virus 

containing any portion of the coding regions of all eight gene segments. 

Page 76 GAO-09-574 High-Containment Laboratories
Appendix III: List of Select Agents and Toxins 

as of November 17, 2008 

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 virus2

Overlap Select Agents and Toxins 

Bacillus anthracis 

Brucella abortus 

 

2

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. 

Page 77 GAO-09-574 High-Containment Laboratories
Appendix III: List of Select Agents and Toxins 

as of November 17, 2008 

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) 

Page 78 GAO-09-574 High-Containment Laboratories
Appendix IV: Biological Agents Recommended 

for BSL-3 Containment That Are Not Select Appendix IV: Biological Agents 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 nonselect-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 Disease 

Bordetella pertussis pertussis (whooping cough)a

Neisseria gonorrhoeae gonorrhea 

M meningitis, septicemia 

Salmonella typhi typhoid fevera

Hepatitis B, C, D viruses hepatitis Ba, hepatitis C, hepatitis D 

Human herpes virus herpes simplex et al. 

Lyssaviruses rabiesa

Retroviruses HIV 

Source: BMBL, 5th Edition. 

a

These agents currently have vaccines available to the public. 

Table 12: Agents Typically Requiring BSL-3 Containment 

Agent Disease 

Chlamydia psittaci psittacosis 

Hanta virus Hanta virus pulmonary syndrome 

Mycobacterium tuberculosis complex tuberculosis 

Non-contemporary human influenza Strains 

(H2N2) 

H2N2 influenza 

Lymphocytic choriomeningitis virus aseptic meningitis, encephalitis 

SARS coronavirus SARSa

West Nile virus “West Nile virus” encephalitis 

Source: BMBL, 5th Edition. 

a

CDC has proposed that this agent be added to the select agents and toxins list. 

Page 79 GAO-09-574 High-Containment Laboratories 
Appendix V: The Army’s 

Requirements for HighContainment Laboratories in 

2001 

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 

Page 80 GAO-09-574 High-Containment Laborato
Appendix V: The Army’s 

Requirements for HighContainment Laboratories in 

2001 

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.1

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 highcontainment 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. 

 

1

In 2007, Army regulation 385-10, the Army Safety Program, provided policies on safety that 

included biological safety. 

Page 81 GAO-09-574 High-Containment Laborato
Appendix VI: CDC’s Integrated Approach to 

Biocontainment at High-Containment Appendix VI: CDC’s Integrated Approach to Laboratories 

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 ‘threelegged’ 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 constructionrelated impacts, rather than typical operations conditions, and all but UPSgenerated life safety required power was lost in B [building] 18. However, 

Page 82 GAO-09-574 High-Containment Laboratories 
Appendix VI: CDC’s Integrated Approach to 

Biocontainment at High-Containment 

Laboratories 

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.” 

Page 83 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the Appendix VII: Comments from the Department of Health and Human Services 

Department of Health and Human Services 

Note: GAO comments 

supplementing those in 

the report text appear at 

the end of this appendix. 

Page 84 GAO-09-574 High-Containment Laboratories 
Appendix VII: Comments from the 

Department of Health and Human Services 

See comment 1. 

See comment 2. 

See comment 3. 

Page 85 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the 

Department of Health and Human Services 

See comment 4. 

See comment 5. 

See comment 6. 

Page 86 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the 

Department of Health and Human Services 

See comment 7. 

See comment 8. 

See comment 9. 

Page 87 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the 

Department of Health and Human Services 

See comment 10. 

Page 88 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the 

Department of Health and Human Services 

Page 89 GAO-09-574 High-Containment Laboratories
Appendix VII: Comments from the 

Department of Health and Human Services 

Page 90 GAO-09-574 

The following are GAO’s responses to the Department of Health and 

Human Service’s (HHS) comments in a letter dated July 20, 2009. 

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. 

GAO Comments 

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 highcontainment 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 highcontainment 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. 

High-Containment Laboratories 
Appendix VII: Comments from the 

Department of Health and Human Services 

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 highcontainment 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. 

Page 91 GAO-09-574 High-Containment Laboratories
Appendix VIII: Comments from the Appendix VIII: Comments from the Department of Agriculture 

Department of Agriculture 

Page 92 GAO-09-574 High-Containment Laboratories 
Appendix VIII: Comments from the 

Department of Agriculture 

Page 93 GAO-09-574 High-Containment Laboratories
Appendix VIII: Comments from the 

Department of Agriculture 

Page 94 GAO-09-574 High-Containment Laboratories
Appendix VIII: Comments from the 

Department of Agriculture 

Page 95 GAO-09-574 High-Containment Laboratories
Appendix IX: 

A

GAO Contact and Staff 

cknowledgments 

Page 96 GAO-09-574 

Appendix IX: GAO Contact and Staff 

Acknowledgments 

Nancy Kingsbury, (202) 512-2700 or kingsburyn@gao.gov 

In addition to the contact named above, Sushil Sharma, Ph.D., DrPH 

(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. 

GAO Contact 

Staff 

Acknowledgments 

High-Containment Laboratories 
Related GAO Products 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 GAO-09-747. Washington, D.C.: July 30, 2009. 

Biosafety Laboratories: BSL-4 Laboratories Improved Perimeter 

Security Despite Limited Action by CDC. GAO-09-851. Washington, D.C.: 

July 7, 2009. 

Biosafety Laboratories: Perimeter Security Assessment of the Nation’s 

Five BSL-4 Laboratories. 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. 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. 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. 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. 

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.

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. 

GAO-05-214. Washington, D.C.: March 8, 2005. 

Combating Bioterrorism: Actions Needed to Improve Security at Plum 

Island Animal Disease Center. GAO-03-847. Washington, D.C.: September 

19, 2003. 

Homeland Security: CDC’s Oversight of the Select Agent Program. 

GAO-03-315R. Washington, D.C.: November 22, 2002. 

(460579) Page 97 GAO-09-574 High-Containment Laboratories
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