High-Containment Laboratories: National Strategy for Oversight Is Needed
Published: 2009-09-21T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: U.S. laboratories working with dangerous biological pathogens (commonly referred to as high-containment laboratories) have proliferated in recent years. As a result, the public is concerned about the oversight of these laboratories. The deliberate or accidental release of biological pathogens can have disastrous consequences. GAO was asked to determine (1) to what extent, and in what areas, the number of high-containment laboratories has increased in the United States, (2) which federal agency is responsible for tracking this expansion and determining the associated aggregate risks, and (3) lessons learned from highly publicized incidents at these laboratories and actions taken by the regulatory agencies. To carry out its work, GAO surveyed and interviewed federal agency officials, (including relevant intelligence community officials), consulted with experts in microbiology, reviewed literature, conducted site visits, and analyzed incidents at high-containment laboratories.
section_title: What GAO Found
paragraphs: The recent expansion of high-containment laboratories in the United Statesbegan in response to the need to develop medical countermeasures after the anthrax attacks in 2001. Understandably, the expansion initially lacked a clear, governmentwide coordinated strategy. In that emergency situation, the expansion was based on individual agency perceptions of the capacity their high-containment labs required as well as the availability of congressionally approved funding. Decisions to fund the construction of high-containment labs were made by multiple federal agencies in multiple budget cycles. Federal and state agencies, academia, and the private sector considered their individual requirements, but an assessment of national needs was lacking. Even now, after more than 7 years, GAO was unable to find any projections based on a governmentwide strategic evaluation of future capacity requirements set in light of existing capacity; the numbers, location, and mission of the laboratories needed to effectively counter biothreats; and national public health goals. Such information is needed to ensure that the United States will have facilities in the right place with the right specifications. Furthermore, since no single agency is in charge of the expansion, no one is determining the aggregate risks associated with this expansion. As a consequence, no federal agency can determine whether high-containment laboratory capacity may now meet or exceed the national need or is at a level that can be operated safely. If an agency were tasked, or a mechanism were established, with the purpose of overseeing the expansion of high-containment laboratories, it could develop a strategic plan to (1) ensure that the numbers and capabilities of potentially dangerous high-containment laboratories are no greater than necessary, (2) balance the risks and benefits of expanding such laboratories, and (3) determine the type of oversight needed. Four highly publicized incidents in high-containment laboratories, as well as evidence in scientific literature, demonstrate that (1) while laboratory accidents are rare, they do occur, primarily due to human error or systems (management and technical operations) failure, including the failure of safety equipment and procedures, (2) insiders can pose a risk, and (3) it is difficult to control inventories of biological agents with currently available technologies. Taken as a whole, these incidents demonstrate failures of systems and procedures meant to maintain biosafety and biosecurity in high-containment laboratories. For example, they revealed the failure to comply with regulatory requirements, safety measures that were not commensurate with the level of risk to public health posed by laboratory workers and pathogens in the laboratories, and the failure to fund ongoing facility maintenance and monitor the operational effectiveness of laboratory physical infrastructure. Oversight plays a critical role in improving biosafety and ensuring that high-containment laboratories comply with regulations. However, some aspects of the current oversight programs provided by the Departments of Health and Human Services and Agriculture are dependent upon entities monitoring themselves and reporting incidents to federal regulators. Since 2001, personnel reliability programs have been established to counter insider risks, but their cost, effectiveness, and impact has not been evaluated.

section_title: Letter
paragraphs: 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. 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.  According to the National Institute of Allergy and Infectious Diseases  (NIAID), these high-containment laboratories were needed to support its  research agenda for developing medical countermeasures against  biothreats. Scientific research on these dangerous pathogens and the  mechanisms by which they cause disease underpins the nation’s ability to  successfully combat infectious diseases and is essential to the  development of new and improved diagnostics, treatments, and preventive  measures for a variety of infectious diseases.
In 2007, we reported on issues associated with the proliferation of high- containment laboratories in the United States, including risks posed by  biosafety incidents that have occurred in the past. 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. In this context, you asked us to address the following  questions:  1.  To what extent, and in what areas, has the number of high- containment laboratories increased in the United States? 2.  Which federal agency is responsible for tracking the expansion of high- containment laboratories and determining the associated aggregate  risks? 3.  What lessons can be learned from highly publicized incidents at high- containment laboratories and actions taken by the regulatory  agencies?
To answer these questions, we interviewed federal agency officials as well  as experts in microbiology, reviewed literature, conducted site visits, and  surveyed 12 federal agencies to determine if they have a mission to track  high-containment laboratories in the United States. We also interviewed  officials from relevant intelligence agencies to determine if they have a  mission to determine insider risks in high-containment laboratories. The  expert panel (see appendix II) that reviewed this report comprised  scientists with substantive expertise in microbiological and select agent  research and the operation of high-containment laboratories.
We conducted our work from September 2005 through June 2009 in  accordance with generally accepted government auditing standards. Those  standards require that we plan and perform the audit to obtain sufficient,  appropriate evidence to provide a reasonable basis for our findings and  conclusions based on our audit objectives. We believe that the evidence  obtained provides a reasonable basis for our findings and conclusions  based on our audit objectives. (See appendix I for our scope and  methodology and appendix II for a list of the experts who reviewed this  report.)
subsections: section_title: Background
subsections: section_title: Level of Risk in High- Containment Laboratories
paragraphs: 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.
section_title: Biosafety Levels for Laboratories Working with Human Pathogens
paragraphs: In the United States, laboratories working with human pathogens are  classified by the type of agents used; activities being conducted; and the  risks those agents pose to laboratory personnel, the environment, and the  community. The Department of Health and Human Services (HHS) has  developed and provided biosafety guidelines outlined in the manual titled  Biosafety in Microbiological and Biomedical Laboratories (BMBL). 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)  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.
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.
section_title: Animal Biosafety Level Criteria for Vertebrate Animals
paragraphs: 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.
section_title: Agricultural Biosafety Levels
paragraphs: 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.
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.
section_title: Containment Levels for Plants
paragraphs: Currently, the BMBL does not provide any comparable classification levels  for laboratories working with plant pathogens.
section_title: Federal Agency Involvement in High- Containment Laboratories and Related Issues
paragraphs: 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. Examples include the following:    The Centers for Disease Control and Prevention (CDC) has its own high- containment laboratories. The Division of Select Agents and Toxins  (DSAT), located within the Coordinating Office for Terrorism  Preparedness and Emergency Response at CDC, regulates federal, state,  academic, commercial, and private laboratories throughout the United  States that possess, use, or transfer select agents. CDC also funds some  laboratory activities carried out in state public health laboratories,  commonly referred to as the Laboratory Response Network (LRN).
The Department of Agriculture (USDA) has its own laboratories, and  APHIS regulates laboratories working with select agents and toxins posing  a risk to animal and plant health or animal and plant products.
The National Institutes of Health (NIH), working through its various  institutes, funds biomedical research, some of which requires high  containment laboratories. NIH has containment and biosafety  requirements that apply to this and other research that it funds when the  research uses recombinant deoxyribonucleic acid (rDNA) molecules. The  NIH rDNA Guidelines provide greenhouse containment standards for  rDNA-containing plants, as well as plant-associated microorganisms and  small animals. NIH has its own high-containment laboratories and has  funded the construction of high-containment laboratories at academic  institutions.
The Food and Drug Administration (FDA) has its own laboratories and  regulates manufacturing of biological products, some of which require  high-containment laboratories.
The Department of Commerce regulates the export of agents and  equipment that have both military and civilian uses and that are often  found in high-containment laboratories.
The Department of Defense (DOD) has its own laboratories and funds  research requiring high-containment laboratories.
The Department of Labor’s Occupational Safety and Health Administration  (OSHA) regulates and inspects private-sector employee safety and health  within high-containment biological laboratories and regulates federal  employee safety and health in these laboratories. However, OSHA does not  have statutory responsibility for the occupational safety and health of (1)  contractor employees performing work at government-owned, contractor- operated sites owned by the Department of Energy (DOE) or (2) state and  local government employees.
The Department of State (DOS) regulates the export of agents and  equipment from defense-related high-containment laboratories. DOS also  maintains a listing of some high-containment laboratories as part of U.S.  commitments under the Biological and Toxin Weapons Convention.
The Department of Justice’s (DOJ) Federal Bureau of Investigation (FBI)  utilizes high-containment laboratories when its forensic work involves  dangerous biological agents and conducts security risk assessments for  the DSAT and APHIS select agent programs.
The Department of Homeland Security (DHS) has its own high- containment laboratories and funds a variety of research requiring high- containment laboratories.
The Department of Energy (DOE) has several BSL-3 laboratories doing  research to develop detection and response systems to improve  preparedness for a biological attack.
The Department of the Interior has its own BSL-3 laboratories for work  with infectious animal diseases.
The Department of Veterans Affairs has BSL-3 laboratories for diagnostic  and research purposes.
The Environmental Protection Agency (EPA) has its own BSL-3  laboratories and also coordinates the use of various academic, state, and  commercial high-containment laboratories nationwide as part of its  emergency response mission (eLRN, environmental laboratory Response  Network).
section_title: Laws, Regulations, and Guidance Pertinent to High-Containment Laboratories
paragraphs: 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. The following is a short summary of pertinent laws, regulations,  and guidance.
subsections: section_title: Pertinent Laws
paragraphs: Following the Oklahoma City bombing in 1995, Congress passed the  Antiterrorism and Effective Death Penalty Act of 1996 to deter terrorism,  among other reasons. Section 511 of title V of this act gave authority to  the HHS Secretary to regulate the transfer, between laboratories, of  certain biological agents and toxins. It directed the Secretary to  promulgate regulations identifying a list of biological agents and toxins— called select agents—that have the potential to pose a severe threat to  public health and safety, providing procedures governing the transfer of  those agents, and establishing safeguards to prevent unauthorized access  to those agents for purposes of terrorism or other criminal activities. In  response to this act, the HHS Secretary established the select agent  program within the CDC.
In reaction to the September 11, 2001, terrorist attacks and the subsequent  anthrax incidents, Congress passed several laws to combat terrorism (to  prevent theft, unauthorized access, or illegal use) and, in doing so,  significantly strengthened the oversight and use of select agents. The USA  PATRIOT Act made it a criminal offense for certain restricted persons— including some foreign aliens, persons with criminal records, and those  with mental defects—to transport or receive select agents. The act also  made it a criminal offense for any individual to knowingly possess any  biological agent, toxin, or delivery system in type or quantity not justified  by a peaceful purpose. Subsequently, Congress passed the Public Health  Security and Bioterrorism Preparedness and Response Act of 2002  (Bioterrorism Act), 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;  requiring coordination/concurrence between USDA and HHS on select  agents and toxins regulated by both agencies (“overlap” agents and  toxins);  requiring the Secretaries of USDA and HHS to establish and maintain a list  of each biological agent and toxin (select agent and toxin) that has the  potential to pose a severe threat to public health and safety, animal or  plant health, or animal or plant products and directing the Secretaries of  HHS and Agriculture to biennially review and republish the select agent  list, making revisions as appropriate to protect the public;  requiring the Secretaries by regulation to provide for registration of  facilities for the possession, use, and transfer of select agents and toxins,  not just for those facilities sending or receiving select agents;  requiring the Attorney General (delegated to the FBI’s Criminal Justice  Information Services Division) to check criminal, immigration, national  security, and other electronic databases with information submitted in the  registration process for all individuals and nongovernmental entities to  determine if the registrant is a restricted person as defined in the USA  PATRIOT Act or has been reasonably suspected by federal law  enforcement or intelligence agencies of committing a federal crime of  terrorism or having known involvement in an organization that engages in  terrorism or is an agent of a foreign power (this is called a security risk  assessment);  requiring the Secretaries to establish a national database that includes the  names and locations of registered entities; the lists of agents and toxins  such entities possess, use, or transfer; and information regarding the  characterizations of such agents and toxins;  requiring the Secretaries to promulgate regulations that include safeguard  and security requirements for persons possessing, using, or transferring a  select agent or toxin commensurate with the risk such an agent or toxin  poses to public, animal, and plant health and safety, including required  notification to the Secretaries and law enforcement agencies of theft, loss,  or release of a listed agent or toxin; and    establishing civil money penalties for persons violating the regulations and  additional criminal penalties for knowingly possessing a select agent or  toxin without registering it or knowingly transferring a select agent or  toxin to an unregistered person.  (See appendix III for the list of select agents and toxins as of November  11, 2008.)
section_title: Pertinent Regulations and Guidance
paragraphs: 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.
Subsequently, the Bioterrorism Act strengthened HHS’s authority to  regulate facilities and individuals that possessed biological agents and  toxins that pose a severe threat to public health and safety, and the  Agricultural Bioterrorism Act granted comparable authority to the USDA  to establish a parallel set of requirements for facilities and individuals that  handle agents and toxins that pose a severe threat to animal or plant  health or animal or plant products. USDA delegated its authority to the  Animal and Plant Health Inspection Service (APHIS). Both CDC and  APHIS issued similar regulations governing the select agent program;  these regulations became effective on April 18, 2005. CDC issued  regulations for select agents posing a threat to public health and safety.  APHIS issued separate but largely identical regulations for select agents  posing a threat to plants and animals. CDC and APHIS share  oversight/registration responsibilities for overlap select agents that pose  threats to both public health and animal health and animal products.
In developing a list of select agents and toxins that have the potential to  pose a severe threat to public health and safety, the HHS Secretary was  required by the Bioterrorism Act to consider the criteria listed below. The  Secretary directed the CDC to convene an interagency working group to  determine which biological agents and toxins required regulation based on  the following criteria:  the effect on human health of exposure to the agent or toxin;  the degree of contagiousness of the agent or toxin and the methods by  which the agent or toxin is transferred to humans;  the availability and effectiveness of pharmacotherapies and immunizations  to treat and prevent any illness resulting from infection by the agent or  toxin; and    any other criteria, including the needs of children or other vulnerable  populations, that the Secretary considers appropriate.
Similarly, the Agricultural Bioterrorism Act required the USDA Secretary  (delegated to APHIS) to consider the following criteria when selecting  biological agents to be included in the list of select agents that pose a  severe threat to animal or plant health or animal or plant products:  the effect of exposure to the agent or toxin on animal or plant health and  on the production and marketability of animal or plant products;  the pathogenicity of the agent or the toxicity of the toxin and the methods  by which the agent or toxin is transferred to animals and plants;  the availability and effectiveness of pharmacotherapies and prophylaxis to  treat and prevent any illness caused by an agent or toxin; and    any other criteria that the Secretary considers appropriate to protect  animal or plant health, or animal or plant products.
Individuals and entities are required to register with CDC or APHIS prior  to possessing, using, or transferring any select agents or toxins. Prior to  registering, entities must designate a responsible official who has the  authority and responsibility to act on behalf of the entity. Receiving a  certificate of registration from the HHS Secretary or the Administrator of  APHIS is contingent on CDC’s or APHIS’s review of the application  package (APHIS/CDC Form 1) and the security risk assessment conducted  by the FBI (composed of database checks and consisting of a report of  criminal convictions and involuntary commitments greater than 30 days  only) on the individual or nongovernmental entity (federal, state, or local  govermental entities are exempt), the responsible official, and any  individual who owns or controls the nongovernmental entity. Registration  may also be contingent upon inspection of the facility. Submission of  additional information—such as a biosecurity, biosafety, or incident  response plan—is required prior to receiving a certificate of registration.  Registration is valid for one physical location and for a maximum of 3  years.
For facilities registered with CDC or APHIS that possess, use, or transfer  select agents, the regulations require the following:  1.  All individuals in the facility needing access to select agents and toxins  must be approved by the Administrator of APHIS or the HHS Secretary  following a security risk assessment by the FBI prior to having access  (access approval is valid for 5 years).  2.  The facility must develop and implement a written security plan  sufficient to safeguard the select agent or toxin against unauthorized  access, theft, loss, or release.  3.  The facility must develop and implement a written biosafety plan  commensurate with the risk of the agent or toxin; the plan must  contain sufficient information on biosafety and containment  procedures. 4.  The facility must develop and implement a written incident response  plan that fully describes the facility’s response procedures for the  theft, loss, or release of a select agent or toxin; inventory  discrepancies; security breaches; severe weather; workplace violence;  bomb threats; suspicious packages; and other possible emergencies at  the facility. 5.  The facility must provide training on biosafety and security to  individuals with access to select agents and to individuals not  approved for access who will work in or visit areas where select  agents or toxins are handled and stored. 6.  The facility must maintain records relating to the activities covered by  the select agent regulations. 7.  The facility must immediately notify CDC or APHIS and appropriate  federal, state, or local law enforcement agencies upon discovering a  theft or loss of a select agent or toxin, and notify CDC or APHIS upon  discovering the release of a select agent or toxin.
As a matter of policy, CDC or APHIS inspects the premises and records of  applicants, including a review of all required plans, before issuing the  initial certificate of registration to ensure that the entity is compliant with  the select agent regulations. Also, CDC and APHIS must be allowed to  inspect, without prior notification, any facility where select agents or  toxins are possessed, used, or transferred. CDC and APHIS perform site  visits in cases where an entity may be adding a select agent or toxin, new  laboratory facility, or new procedure that requires verification of the  entity’s biosafety plans and procedures. Other inspections performed by  CDC and APHIS include follow-up inspections based on observations from  audits performed by federal partners, compliance inspections, and  investigations of reported incidents that may have involved biosafety or  security concerns that could affect public, animal, and plant health and  safety. CDC and APHIS use specific checklists to guide their inspections.  CDC and APHIS developed these checklists from the select agent  regulations and the BMBL, and they are available at  www.selectagents.gov. The BMBL has become the code of practice for  laboratory principles, practices, and procedures.
If CDC or APHIS discovers possible violations of the select agent  regulations, several types of enforcement actions may occur:    Administrative actions: CDC and APHIS may deny an application or  suspend or revoke a registered entity’s certificate of registration if the  individual or entity, responsible official, or owner of the entity is  reasonably suspected of criminal violations or does not comply with the  select agent regulations or if denial, suspension, or revocation is necessary  to protect public, animal, or plant health and safety. A suspension can be  for all select agent work at a registered entity or be specific to particular  agents.
Civil Money Penalties or Criminal Enforcement: CDC refers possible  violations of the select agent regulations to the HHS Office of Inspector  General (OIG). The HHS-OIG can levy civil money penalties (for an  individual, up to $250,000 for each violation and, for an entity, up to  $500,000 for each violation) or recommend criminal enforcement  (imprisonment for up to 5 years, a fine, or both). As of April 29, 2009,  CDC’s DSAT had referred 48 entities to the HHS-OIG for violating select  agent regulations. HHS-OIG had levied $1,997,000 in civil money penalties  against 13 of these entities. Information regarding these entities can be  found on the following Web sites:  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.
The laws and regulations discussed above provide requirements for  individuals and entities possessing, using, or transferring select agents and  toxins but do not apply universally to high-containment laboratories.  However, guidance for operating high-containment laboratories that is not  legally mandatory is available. Pertinent guidance includes HHS’s BMBL  manual and the NIH Guidelines for Research Involving Recombinant  DNA Molecules.
HHS’s BMBL Manual: The BMBL, prepared by NIH and CDC, categorizes  laboratories on four biosafety levels (BSL) based on risk criteria, with  BSL-4 laboratories being utilized for the study of agents that pose the  highest threat risk to human health and safety. The BMBL describes a code  of practice for biosafety and biocontainment in microbiological,  biomedical, and clinical laboratories. The BMBL serves as the primary  recognized source of guidance on the safe practices, safety equipment, and  facility containment needed to work with infectious agents. The first  publication was in 1984, and the most recent (5th edition) was published  electronically in 2007. The select agent regulations reference the BMBL as  a document to consider when entities are developing their written  biosafety plans. Even though the BMBL is issued as a guidance document,  DSAT and APHIS have incorporated certain elements of it into their  inspection checklists as a requirement of the select agent program.
The BMBL states that (1) biosafety procedures must be incorporated into  the laboratory’s standard operating procedures or biosafety manual, (2)  personnel must be advised of special hazards and are required to read and  follow instructions on practices and procedures, and (3) personnel must  receive training on the potential hazards associated with the work and the  necessary precautions to prevent exposure. Further, the BMBL (5th  edition) provides guidance on biosecurity, such as methods of controlling  access to areas where agents are used or stored. The BMBL also states  that a plan must be in place for informing police, fire, and other emergency  responders concerning the type of biological materials in use in the  laboratory areas.
NIH Guidelines for Research Involving Recombinant DNA  Molecules: Some of the work in BSL-3 and BSL-4 laboratories in the  United States involves rDNA, and the standards and procedures for  research involving rDNA are set by the NIH Guidelines for Research  Involving Recombinant DNA Molecules (NIH rDNA Guidelines).  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.
section_title: The Number of BSL-4 and BSL-3 Laboratories and Their Workforce Are Increasing in Different Sectors throughout the United States
paragraphs: Since 2001, the number of BSL-4 and BSL-3 laboratories in the United  States has increased, and this expansion has taken place across federal,  state, academic, and private sectors and throughout the United States.  Federal officials and experts believe that while the number of BSL-4  laboratories in the United States is known, the number of BSL-3  laboratories is unknown. Information about the number, location,  activities, and ownership is available for high-containment laboratories  that are registered with the DSAT or APHIS select agent programs but not  for those outside the program.
A number of issues are associated with determining the overall number of  BSL-3 and BSL-4 laboratories. In our discussions with federal agency  officials and experts and in our review of the literature, we found that the  total number depended upon how the question was phrased. While data  were generally available on the number of facilities or sites that contained  a BSL-3 or BSL-4 laboratory, the precise number of independent rooms  within those facilities qualifying as BSL-3 or BSL-4 laboratories was not  generally specified. Some facilities contain more than one actual  laboratory. For example, while CDC has two facilities with BSL-4 capacity,  one of the facilities actually contains two separate BSL-4 laboratories,  while the other has four separate BSL-4 laboratories. These officials and  experts also told us that counting the number of laboratories is  problematic because the definition of the term “laboratory” varies. A more  meaningful measure is determining the net square footage of working BSL- 4 space. However, this information is often not available. In addition, there  also are methodological issues associated with determining whether a  laboratory is operational or not.
The expansion of high-containment laboratories in the United States began  in response to the emergency situation resulting from the anthrax attacks  in 2001. Understandably, the expansion initially lacked a clear,  governmentwide coordinated strategy. In that emergency situation, the  expansion was based on the perceptions of individual agencies about the  capacity required for their high-containment laboratory activities as well  as the availability of congressionally approved funding. Decisions to fund  the construction of high-containment laboratories were made by multiple  federal agencies in multiple budget cycles. Federal and state agencies,  academia, and the private sector considered their individual requirements,  but a robust assessment of national needs was lacking. Since each agency  has a different mission, an assessment of needs, by definition, is at the  discretion of the agency. We have not found any national research agenda  linking all these agencies that would have allowed for such a national  needs assessment. Even now, after more than 7 years, we have not been  able to find any detailed projections based on a governmentwide strategic  evaluation of future capacity requirements in light of existing capacity; the  numbers, location, and mission of the laboratories needed to effectively  counter biothreats; and national public health goals. Without this  information, there is little assurance of having facilities in the right places  with the right specifications to meet a governmentwide strategy.
subsections: section_title: The Number of BSL-4 Laboratories Is Increasing in Some Sectors
paragraphs: For most of the past 50 years, there were only two entities with BSL-4  laboratories in the United States: federal laboratories at USAMRIID at Fort  Detrick, Maryland, and at the CDC in Atlanta, Georgia. Between 1990 and  2000, three new BSL-4 laboratories were built: (1) the first BSL-4 university  laboratory (a glovebox, rather than a conventional laboratory) 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. 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.
Since the anthrax attacks in 2001, seven new BSL-4 facilities are in the  planning, construction, or commissioning stage. Four of these facilities are  in the federal sector, two are in the academic sector, and one is in the  state/local government sector.
The following are the BSL-4 facilities in the planning, construction, or  commissioning stage in the federal sector:  (1) NIAID Integrated Research Facility, Fort Detrick, Maryland;  (2) DHS National Biodefense Analysis and Countermeasure Center, Fort  (3) DHS National Bio- and Agro-Defense Facility (NBAF), Manhattan,  (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.
The total number of BSL-4 laboratorieswill increase from 7 to 13 when  these laboratories become operational.  The locations of the BSL-4  laboratories that are currently registered, under construction, or in the  planning stage are shown in figure 1.
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.
section_title: BSL-3 Laboratories Are Being Built in All Sectors throughout the United States
paragraphs: CDC officials stated that unlike the case with BSL-4 laboratories,  operators might build BSL-3 laboratories and not work with select agents.  For example, when building new laboratories or upgrading existing ones,  many laboratory owners may build to meet BSL-3 level containment, often  in anticipation of future work, even though they intend for some time to  operate at the BSL-2 level with BSL-2 recommended agents. Consequently,  CDC officials acknowledged that they do not know the total number of  BSL-3 laboratories in the United States that are not registered to possess,  use, or transfer select agents.
In April 2007, we conducted a Web-based survey—based on a search of  publicly available sources—of contacts knowledgeable about high- containment laboratories (for example, biosafety officers). 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).
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.
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.)
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. 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.
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.
Additionally, NIAID recently funded the construction of 13 BSL-3 Regional  Biocontainment Laboratories (RBL) within the academic research  community at the following universities:  (1)  (2)  (3)  (4)  (5)  (6)  (7)  (8)  (9)  (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,  Colorado State University, Fort Collins, Colorado;  Duke University Medical Center, Durham, North Carolina;  George Mason University, Fairfax, Virginia;  University of Hawaii, Manoa, Hawaii;  University of Louisville, Louisville, Kentucky;  University of Medicine and Dentistry of New Jersey; Newark,   New Jersey;  Tufts University, Grafton, Massachusetts;  Tulane National Primate Research Center, Covington, Louisiana;  University of Alabama, Birmingham, Alabama;  Tennessee.
NIAID is constructing RBLs to provide regional BSL-3 laboratory capacity  to support NIAID’s Regional Centers of Excellence for Biodefense and  Emerging Infectious Diseases Research. The RBLs are distributed  regionally around the country.
Figure 3 shows the sites of NIAID-funded RBLs in the United States.
section_title: The Workforce in BSL-3 and BSL-4 Laboratories Is Increasing
paragraphs: 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.
In 2004, 8,335 individuals had access approvals. This number increased to  10,365 by 2008. 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.
subsections: section_title: Budget and Resources for Select Agent Oversight Program
paragraphs: The increase in the number of entities and high-containment laboratories  that work with select agents has implications for federal oversight. As part  of regulatory requirements, DSAT and APHIS staff inspect each entity  prior to issuing a certificate of registration to ensure that the entity is in  compliance with the select agent regulations. In addition, as part of the  entity’s renewal process, which occurs every 3 years, DSAT and APHIS  inspectors are required to reinspect the entity. APHIS performs additional  annual compliance inspections between the 3-year renewal cycles even if  there is no change. DSAT performs additional inspections when an entity  adds a select agent or toxin, a new laboratory facility, or a new procedure  that requires verification of the entity’s biosafety plans and procedures.
As mentioned previously, the number of entities and the number of BSL-3  laboratories working with select agents increased between 2004 and 2008.  As a result of this increase, DSAT now has to inspect more entities.
As shown in table 8, DSAT had a budget of $14 million and had 25 full-time  equivalent inspectors (5 federal and 20 contract) in fiscal year 2004, when  the interim regulations first provided for certificates of registration.  However, its budget decreased between 2004 and 2008. In 2004, DSAT was  responsible for providing oversight to 150 entities with 415 BSL-3  laboratories. In 2008, DSAT provided oversight to 242 entities with 1,362  BSL-3 laboratories with a decreased budget and only 3 more inspectors (11  federal and 17 contract). No evaluations are available to determine how  this increased mission and decreased budget affected the quality of  oversight.
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.
section_title: No Federal Agency Has the Mission to Track the Expansion of All High- Containment Laboratories and Regulate Biosafety in the United States
paragraphs: 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.
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.
While some federal agencies do have a mission to track a subset of BSL-3  and -4 laboratories that work with select agents and know the number of  those laboratories, no single regulatory agency has specific responsibility  for biosafety in all high-containment laboratories in the United States.
According to some experts and federal agency officials, the oversight of  these laboratories is fragmented and relies on self-policing. For example, if  an entity is registered under the select agent regulations, DSAT or APHIS  provides oversight. On the other hand, if an entity receives federal funding  from NIH for rDNA research, the NIH Office of Biotechnology Activities  provides oversight. These agencies assume that all risks would be dealt  with by the entities’ self-regulation, consistent with the laboratory practice  guidelines developed by NIH and CDC.
subsections: section_title: Risks Associated with the Expansion of High- Containment Laboratories
paragraphs: 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. While some agencies have the  specific responsibility for determining threats from rogue nations and  foreign and domestic terrorists, we found that no agency has the mission  to proactively determine the threat from insiders.
According to most experts, there is a baseline risk associated with any  high-containment laboratory. With expansion, the aggregate risks increase.  However, no agency has the mission to determine whether the risks  associated with expansion increase in proportion to the number of  laboratories or at some different rate or whether factors such as location  and resource limitations may affect the risk ratio. Because CDC and USDA  regulations require that entities registering with the select agent program  assess only the risks associated with their individual laboratories, CDC  and USDA do not have the mission to determine the aggregate risks  associated with the expansion of high-containment laboratories that work  with select agents.
High-containment laboratories can pose health risks for individual  laboratory workers as well as the surrounding community. However, the  relative risk profile of new versus more established laboratories is not  known. According to CDC officials, the risks from accidental exposure or  release can never be completely eliminated, and even laboratories within  sophisticated biological research programs—including those most  extensively regulated—have had and will continue to have safety failures.
In addition, while some of the most dangerous agents are regulated under  the CDC-APHIS select agent program, high-containment laboratories also  work with agents not covered under this program. Laboratories outside  the select agent program, especially those working with emerging  infectious diseases, can also pose biosafety risks from accidental exposure  or release. Several of these biological agents are listed in the BMBL as  requiring BSL-3 practices, including West Nile Virus and Hantavirus. (See  appendix IV for a list of biological agents recommended to be handled in  BSL-3 laboratories that are not select agents).
Consequently, laboratories having capabilities to work with biological  agents, even though they do not posses select agents, are not currently  subject to oversight. These laboratories also have associated biosecurity  risks because of their potential as targets for terrorism or theft by either  internal or external perpetrators. laboratories outside the select agent  program also represent a capability that can be paired with dangerous  pathogens and skilled but ill-intentioned scientists to become a threat.
section_title: Unlike the United Kingdom, the United States Has No Laws to Assist in Tracking High- Containment Laboratories
paragraphs: Currently, no laws in the United States specifically focus on all high- containment laboratories. In the United Kingdom (U.K.), by contrast, new  high-containment laboratories that work with human, animal, or  genetically modified (GM) pathogens need to notify the U.K. regulator (the  Health and Safety Executive (HSE)) and receive either consent (for GM  human pathogens) or license (for animal pathogens) before they  commence their activities.
Prior to construction of the facility, there is no requirement to inform HSE  (except for planning authorities, who look at land use and building  quality); however, in practice, HSE staff are involved at the design stage  and at various points during the construction process. According to HSE  staff, this early involvement has been extremely helpful in ensuring that  new facilities meet the standards set out in the legislation and supporting  guidance (related to the management, design, and operation of high- containment laboratories).
This involvement has also enabled HSE to address the application of new  technologies in high-containment laboratories (e.g., alkaline hydrolysis for  waste destruction as an alternative to incineration). While the legislation  in the U.K. states that a BSL-4 laboratory must have an incinerator on site  for disposal of animal carcasses, HSE staff told us that they have been  involved in discussions relating to new facilities where the entities wanted  to replace the incinerator with an alkaline hydrolysis system. Similarly, all  BSL-4 laboratories use cabinet lines (for human pathogens). HSE staff  have been in discussion with entities about proposals to move to a suited  system rather than rely entirely on primary containment. HSE staff told us  that they are recognizing that technologies change and there may be good  reasons to move away from established procedures, assuming that the  alternatives being proposed provide a high degree of assurance that  biosafety and biosecurity will not be compromised by the changes.
In April 2010, the U.K. plans to implement a single regulatory framework  for human, animal, and genetically modified pathogens that will include a  legal requirement for duty holders to consult the regulatory authority prior  to construction and for HSE to be a statutory consultee as part of the  planning authorization.
section_title: Lessons Learned from Four Incidents Highlight the Risks Inherent in the Expansion of High- Containment Laboratories
paragraphs: We reviewed four incidents that highlight the risks inherent in the  expansion of high-containment laboratories: alleged insider misuse of a  select agent and laboratory; Texas A&M University’s (TAMU) failure to  report to CDC exposures to select agents in 2006; power outages at CDC’s  high-containment laboratories in 2007 and 2008; and the release of foot- and-mouth disease virus in 2007 at the Pirbright facility in the U.K.
We reviewed these incidents in detail because they represented different  types of risk associated with high-containment laboratories and because a  significant amount of information was available concerning them.  According to the experts we talked with, many other incidents and  accidents have occurred, mainly as a result of human error or equipment  failure. Fortunately, most incidents/accidents do not have serious  consequences for the health of laboratory workers, the general population,  or the environment. The experts we spoke with also stated that it is highly  probable that many incidents go unreported and unrecorded because of  the lack of such serious consequences. Such underreporting represents  lost opportunities to analyze and learn lessons that can provide a basis for  continuing improvement and maintenance of laboratory safety.
We are not making any generalizations about the magnitude of the  problem involving other laboratories. However, the lessons we have  identified highlight ways to improve biosafety and biosecurity. These  lessons also have implications for institutional and federal oversight.
subsections: section_title: Incident 1: Alleged Insider Misuse of a Select Agent and Laboratory
paragraphs: 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. The  letters led to the first U.S. cases of anthrax disease related to bioterrorism,  and the subsequent investigation by FBI has been called “Amerithrax.”
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. USAMRIID is the only DOD laboratory with the capability to  study highly dangerous pathogens requiring maximum containment at  BSL-4. Dr. Ivins had helped develop an anthrax vaccine for U.S. troops and  was in charge of producing large quantities of wet anthrax spores for  research.
Immediately following the anthrax mailings in 2001, FBI took  contaminated evidence to USAMRIID for analysis. Dr. Ivins was tasked by  USAMRIID management to analyze the samples of spores sent through the  mail and was also a technical consultant to the FBI in the early months of  investigation. In March 2003, Dr. Ivins and two of his colleagues at  USAMRIID received the Decoration for Exceptional Civilian Service—the  highest award given to DOD civilian employees—for helping solve  technical problems in the manufacturing of licensed anthrax vaccine.
In December 2001, one of Dr. Ivins’ coworkers told Dr. Ivins that she  observed on several occasions unsafe handling procedures by Diagnostic  System Division personnel. She also told him that she might have been  exposed to anthrax spores when handling an anthrax-contaminated letter.  Dr. Ivins began sampling areas in the laboratory space that might have  been contaminated with anthrax. He took samples from the shared office  areas and later decontaminated her desk, computer, keypad, and monitor.  However, he neither documented this incident in the Army record log  book nor notified his superiors. He later acknowledged to Army officials  that this was a violation of protocol. Dr. Ivins’ behavior was detailed in an  Army investigation conducted in response to a second round of sampling  he conducted in April, but his name did not surface at that time as a  suspect in the anthrax attacks.
After a spill incident inside of suite B-3 in building 1425 in April 2002, Dr.  Ivins conducted a second round of unauthorized sampling of his shared  office space and cold side areas outside of suite B-3. These findings were  reported and sparked a buildingwide sampling inspection. An inspection  conducted by the Army 7 months after the anthrax mailing found that suite  B-3 in building 1425 at USAMRIID was contaminated with anthrax in four  rooms of suite B-3 (306, 304, cold room, and 313 (Dr. Ivins’s laboratory))  and that the bacteria had escaped from secure to unprotected areas in the  building. All the areas outside of suite B-3 that tested positive were  associated with Dr. Ivins and members of the Bacteriology Division. The  inspection report stated that “safety procedures at the facility and in  individual laboratories were lax and inadequately documented; that safety  supervision sometimes was carried out by junior personnel with  inadequate training; and that exposures of dangerous bacteria at the  laboratory, including anthrax, had not been adequately reported.” (See  appendix V for additional information on the U.S. Army’s requirements for  high-containment laboratories at the time of the 2001 anthrax incidents.)
In 2005, the FBI investigation began to shift to a particular laboratory at  USAMRIID, and it began to focus on Dr. Ivins as a suspect in 2007.  According to the FBI, Dr. Ivins had the necessary expertise and equipment  to make the anthrax powder in his laboratory. Specifically, at the time of  the anthrax mailings, Dr. Ivins possessed extensive knowledge of various  anthrax production protocols. He was adept at manipulating anthrax  production and purification variables to maximize sporulation and  improve the quality of anthrax spore preparations. He also understood  anthrax aerosolization dosage rates and the importance of purity,  consistency, and spore particle size due to his responsibility for providing  liquid anthrax spore preparations for animal aerosol challenges. He also  had used lyophilizers, biological safety cabinets, incubators, and  centrifuges in vaccine research. Such devices are considered essential for  the production of the highly purified, powdered anthrax spores used in the  fall 2001 mailings.
According to the FBI’s application for a search warrant, at the time of the  attack, Dr. Ivins “(1) was the custodian of a large flask of highly purified  anthrax spores that possess certain genetic mutations identical to the  anthrax used in the attacks; (2) Ivins has been unable to give investigators  an adequate explanation for his late night laboratory work hours around  the time of both anthrax mailings; (3) Ivins has claimed that he was  suffering serious mental health issues in the months preceding the attacks,  and told a coworker that he had ‘incredible paranoid, delusional thoughts  at times’ and feared that he might not be able to control his behavior; (4)  Ivins is believed to have submitted false samples of anthrax from his  laboratory to the FBI for forensic analysis in order to mislead  investigators; (5) at the time of the attacks, Ivins was under pressure at  work to assist a private company that had lost its FDA approval to  produce an anthrax vaccine the Army needed for U.S. troops, and which  Ivins believed was essential for the anthrax program at USAMRIID; and (6)  Ivins sent an e-mail to a friend a few days before the anthrax attacks  warning her that ‘Bin Laden terrorists for sure have anthrax and sarin gas’  and have ‘just decreed death to all Jews and all Americans,’ language  similar to the anthrax letters warning ‘WE HAVE THIS ANTHRAX ...  DEATH TO AMERICA ... DEATH TO ISRAEL.’” The FBI stated that in late  2005, forensic science (genetic analysis) used to trace the anthrax used in  the 2001 attack had genetic markers consistent with the anthrax spores  kept in a flask in the refrigerator in Dr. Ivins’s laboratory at Ft. Detrick,  Maryland, to spores in the letters.
During this time, Dr. Ivins kept his security clearance and passed a  polygraph-assisted interrogation (also known as a “lie detector test”) in  which he was questioned about his possible participation in the anthrax  attacks. In November 2007, he was denied access to all high-containment  laboratories and, in March 2008, to all laboratories at USAMRIID. It should  be noted that while Dr. Ivins was denied access to the high-containment  suites in November 2007, he was certified at that time into the personnel  reliability program. On July 10, 2008, Dr. Ivins attended a briefing on a new  pneumonic plague vaccine under development at the Army’s laboratory.  After this briefing, he was escorted to a psychiatric evaluation off the  installation by local authorities, and his access rights to the entirety of  USAMRIID were withdrawn by the laboratory commander. An order was  subsequently issued to installation security to prevent Dr. Ivins from  entering the installation unescorted. A written bar order was signed with a  plan to serve the document to Dr. Ivins. Before service of the order  occurred, he died of a drug overdose on July 29, 2008.
subsections: section_title: Lessons Learned: Insider Risk and Inventory Control of Biological Agents
paragraphs: This incident highlights two lessons: (1) an ill-intentioned insider can pose  a risk not only by passing on confidential information but also by  removing dangerous material from a high-containment laboratory, and (2)  it is impossible to have completely effective inventory control of biological  material with currently available technologies. It is impossible to know the  exact number of bacteria or virus in a laboratory’s inventory or working  stocks at any specific time. At Ft. Detrick, ineffective procedures for the  control of inventories and the unlimited use of laboratory facilities  allegedly allowed Dr. Ivins the opportunity to pursue his own ends. As the  number of high-containment laboratories increases, there will be an  increase in the pool of scientists with expertise and, thus, the  corresponding risk from insiders may also increase.
Insiders Can Misuse Material and Facilities  There are arguably two aspects to insider risk: the motive of the insider  and the ability to misuse material and laboratory facilities. These two  elements need to be understood if effective countermeasures are to be  instituted in a proportionate manner. In this case, assuming Dr. Ivins was  the culprit, no one can conclusively determine what motivated his actions  since he committed suicide before his motive could be determined.
With regard to the ability to misuse the facility, FBI records show that Dr.  Ivins had unlimited access to material and laboratory facilities. However, it  is still unclear whether the spores in the letters came directly from the  flask under Dr. Ivins’s control or involved some further illicit culturing. In  either case, material was illegally removed and laboratory facilities were  misused—at a minimum, to dry and process the spores. It follows that  research laboratories clearly represent a significant capability that can be  potentially misused, and this capability is growing with the increasing  number of high-containment laboratories. While efforts to strengthen  inventory controls, assess and monitor personnel, and prevent facility  misuse (for example, by video monitoring) have been undertaken to  address insider threats, we are not aware of any evaluation of the  effectiveness of these measures. While there are clearly major difficulties  in imposing such controls in research laboratories, insider risk needs to be  recognized and evaluated.
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.
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. In its report, the board recommended that “it is appropriate to  enhance personnel reliability measures for individuals with access to  select agents, but promulgation of a formal, national personnel reliability  program is unnecessary at this time.”
On February 11, 2004, DOD issued a directive (5210.88), “Safeguarding  Biological Select Agents and Toxins” (BSAT). This directive established  security policies and assigned responsibilities for safeguarding select  agents and toxins. Specifically, this directive established, among other  things, the following DOD policy:  “Individuals who have a legitimate need to handle or use biological select  agents and toxins, or whose duties afford access to storage and work  areas, storage containers and equipment containing biological select  agents or toxins shall be screened initially for suitability and reliability.  This means that they shall be emotionally and mentally stable,  trustworthy, and adequately trained to perform the assigned duties and  shall be the subject of a current and favorably adjudicated National  Agency Check with Local Agency Checks and Credit Checks for military  and contractor employees and an Access National Agency Check with  credit checks and written inquiries for civilian employees with a  reinvestigation every 5 years and they shall be evaluated on a continuing  basis using the criteria issued by the [Under Secretary of Defense for  Intelligence.]”
On April 18, 2006, DOD issued Instruction 5210.89, “Minimum Security  Standards for Safeguarding Select Agents and Toxins.” This instruction  established, among other things, the criteria and requirements for  personnel regarding a biological personnel reliability program (BPRP).  The purpose of a BPRP is to (1) ensure that each individual, who has  authorized access to BSAT and/or supervises personnel with access to  biological restricted areas and BSAT, including responsible and certifying  officials, meets the highest standards of integrity, trust, and personal  reliability and (2) identify any potential risk to public health, safety, and  national security.
Following the announcement of the FBI anthrax investigation at  USAMRIID, the Secretary of the Army organized a task force on August 7,  2008, to evaluate the U.S. Army biological surety program, including  safety, security, and personnel reliability. In response, the Inter-Service  Council for Biosecurity and Biosafety, General Officer Steering  Committee, issued a report on December 12, 2008. This report focused on  seven areas: transportation of select agents and toxins; biological safety;  biological security/physical security; inspection; personnel reliability  program/foreign personnel; inventory/accountability of select agents and  toxins; and training of personnel. Review of all seven areas indicated that  armed service policies, regulations, standards, and procedures in effect  before 2008 met or exceeded all federal and DOD requirements. The  services, however, agreed on the need to establish common standards in  each area. In addition, on March 10, 2008, the Interagency Security  Committee Standard defined the criteria and process to be used in  determining the facility security level of a federal facility as the basis for  implementing governmentwide facility security standards.
In October 2008, the office of the Under Secretary of Defense for  Acquisition, Technology, and Logistics asked the Defense Science Board  Task Force on DOD Biological Safety and Security 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.”
In October 2008, the White House Office of Science and Technology Policy  asked the National Science Advisory Board for Biosecurity (NSABB) to  recommend strategies for enhancing personnel reliability among  individuals with access to biological select agents and toxins. Specifically,  the NSABB was asked to identify the optimal framework for ensuring  personnel reliability so that the need for biosecurity was balanced with  rapid progress in the life sciences. The NSABB concluded in its report that  “there is currently insufficient evidence of the effectiveness of personnel  reliability program measures towards mitigating the risk of an insider  threat to warrant the additional significant burden on research  institutions.”  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.  The executive order asked the working group to submit to the President,  no later than 180 days after the date of the order, an unclassified report,  with a classified annex as required, that sets forth the following:  “a summary of existing laws, regulations, guidance, and practices with  respect to security and personnel assurance reviewed under subsection  (a) of this section and their efficiency and effectiveness;  recommendations for any new legislation, regulations, guidance, or  practices for security and personnel assurance for all federal and  nonfederal facilities;    options for establishing oversight mechanisms to ensure a baseline  standard is consistently applied for all physical, facility, and personnel  security and assurance laws, regulations, and guidance at all federal and  nonfederal facilities; and    a comparison of the range of existing personnel security and assurance  programs for access to biological select agents and toxins to personnel  security and assurance programs in other fields and industries.”
The working group submitted its draft report and recommendations to the  White House on July 9, 2009. According to HHS, the draft report is to be  formally reviewed and accepted by the co-chairs—the Secretaries of  Defense and Health and Human Services—before it is made public.
While it may be possible to quantify the financial costs required to initiate  and maintain enhanced oversight procedures—such as controls of  inventories and laboratory usage—the impact of such procedures on work  output is unquantifiable but nevertheless very real. According to some  experts and high-containment laboratory scientists, intrusive personnel  reliability programs can also have an adverse impact on staff work  effectiveness.
Accordingly, the security benefits achieved by such procedures must be  evaluated to obtain some understanding of the cost/benefit ratio. Such an  evaluation could incorporate various stress tests and assessments of  procedures against a range of risk scenarios. Effective evaluation could  improve the cost/benefit ratio by concentrating on procedures with higher  returns on investment and could be more acceptable to laboratory  personnel by demonstrating objective benefits. Regular reevaluation is  critical to avoid adding oversight procedures on a subjective rather than  objective basis.
Inventory Procedures Did Not Impede Insider Misuse of Agents  Prior to the fall of 2001, there were no effective inventory control  procedures at USAMRIID—or indeed other institutions that worked with  select agents—that would have impeded insider misuse of such agents.  Anthrax spores were held in a liquid solution in a flask (RMR-1029) that  originally (October 22, 1997) contained 1000 ml of spore suspension with a  concentration of 3x10 spores/ml. While the flask had been under the  control of Dr. Ivins since 1997, other laboratory staff may also have had  access to it. However, no one in USAMRIID was specifically responsible  for monitoring the use of materials by scientists. According to USAMRIID  officials, Dr. Ivins’s laboratory notebook contained a record of the  amounts of material removed at various times between 1997 and 2004,  when the FBI finally removed the flask from USAMRIID. Additional  undocumented removals from the flask could have been disguised simply  by adding water to restore the volume. This would have reduced the spore  concentration, but this concentration was apparently never checked. Even  if it had been, experts told us that the normal biological experimental error  involved in counting spores could have disguised the loss of up to 5  percent of the material.
It is unclear whether the anthrax spores put in the letters came directly  from the flask after being dried or whether a very small and undetectable  quantity from the flask was cultured to produce enough new spores for the  letters. In either scenario, the self-replicating nature of microorganisms  and the inherent error associated with determining the absolute number of  microorganisms in solution make inventory control a formidable if not  impossible task with currently available technologies.
section_title: Actions Taken by the Regulatory Agency—DSAT— Subsequent to the Incident
paragraphs: 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.
section_title: Incident 2: Safety Violations by a University
paragraphs: 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.
subsections: section_title: Barriers to Reporting Laboratory Accidents
paragraphs: TAMU is registered with DSAT and approved for work on several select  agents. TAMU has several BSL-3 laboratories and works extensively on  animal diseases, including those caused by the select agents Brucella  melitensis, Brucella abortus, and Brucella suis. Brucella can cause  brucellosis in humans, a disease causing flu-like symptoms, such as fever  and fatigue. In severe cases, it can cause infections of the central nervous  system. TAMU is also registered for use of Coxiella burnetii, an animal  agent that can cause Q fever in humans.
In February 2006, a laboratory worker from a non-select-agent laboratory  was helping out with an experiment to aerosolize Brucella. The laboratory  worker had no familiarity with the specifics of working with Brucella but  did have experience working with the aerosol chamber. It was later  determined that the laboratory worker had been exposed to the agent  while cleaning the chamber after the experiment was run.
At the time of the exposure, neither the exposed worker nor anyone else  had any indication that an exposure had taken place. In fact, DSAT  inspectors were on campus days after the Brucella exposure for a routine  inspection but uncovered nothing that alerted them to what had  happened. Symptoms did not start to appear in the exposed worker until  more than a month after the exposure, and then the symptoms were flu- like. Confirmation of brucellosis was not made until another month had  passed and the symptoms had worsened. However, once the brucellosis  was identified, the worker notified appropriate authorities at TAMU. But  no report was subsequently made to DSAT (as required by federal  regulation), and a year passed before—by chance—an independent  watchdog group reviewing unrelated documentation acquired through  Texas’s freedom of information law, uncovered the lapse in reporting. This  prompted TAMU to notify DSAT.
section_title: Training of Laboratory Personnel
paragraphs: 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. According to DSAT, TAMU failed to report to  DSAT that it was conducting aerosolization work with Brucella. Therefore,  DSAT had no reason to verify training, experimental plans, and risk  assessments during its inspections.
According to select agent regulations, all staff—not only staff that have  access to select agents or toxins, but also staff that will work in or visit  areas where select agents are handled or stored—are required to be  trained in the specifics of any agent before they work with it. The training  must address the particular needs of the individual, the work they will do,  and the risks posed by the select agents and toxins. However, the worker  at TAMU did not receive training in the specifics of Brucella, including its  characteristics, safe handling procedures, and potential health effects.  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.  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).
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.
section_title: Medical Provider Lacked Information to Diagnose Possible Infection Quickly
paragraphs: At the time of the exposure to Brucella at TAMU on February 9, 2006, the  laboratory worker and others in the laboratory did not realize she had  been infected. In fact, DSAT conducted a routine inspection of TAMU on  February 22, 2006—13 days after the exposure—but had no way of  knowing that it had happened. According to the exposed worker, she first  fell ill more than 6 weeks after the exposure. At that time, the first  consultation with her physician indicated that she had the flu. Institutions  generally do not give medical providers information about the specific  agents that laboratory staff work with. Therefore, the physician was not  alerted to the possibility that the worker’s symptoms could be the result of  exposure to an infectious agent. After the symptoms persisted, a  consultation with an infectious disease specialist confirmed that the  laboratory worker’s blood contained an unknown microorganism. At that  point, the worker recalled her work with Brucella weeks earlier. The  Texas State Public Health Laboratory confirmed the infection with  Brucella on April 16, 2006—62 days after the exposure. During the interim,  the worker had resumed her normal activities.
By the time the diagnosis was made, the exposed laboratory worker had  become seriously ill. The delay in recognizing the infection resulted in  delay of appropriate treatment, thus aggravating her condition. Such a  misdiagnosis is not uncommon with infectious diseases, as the initial  symptoms often appear flu-like, and brucellosis is not generally endemic in  the population. According to DSAT, the worker might have developed an  even more severe infection, possibly affecting her central nervous system  or the lining of her heart, if the worker had not recalled the experiment  with Brucella and alerted her physician to this fact. The physician might  have been able to correctly diagnose the infection more quickly if the  physician had been informed of the agent the individual worked with.
In this incident, it was fortunate that transmission of brucellosis beyond  the initial exposed individual was difficult and that there was no risk of the  infection spreading to the surrounding community. Many other agents— including those that are not select agents (such as SARS coronavirus and  M. tuberculosis)—cause diseases that are transmitted from human to  human through coughing or fluid transfer.
section_title: Confusion over the Definition of Exposure
paragraphs: In addition to the incident of exposure to Brucella, DSAT noted that  TAMU failed to report several incidents of potential exposure to Coxiella  burnetii—a select agent and the causative agent for Q fever in humans.  While the Brucella exposure eventually became apparent because of  clinical symptoms in the laboratory worker, the C. burnetii incidents  raised questions about what constitutes sufficient evidence of an exposure  that the entity is required to report to DSAT.
For C. burnetii and other agents, periodically measuring the titer or  antibody levels within the blood serum of laboratory workers working  with those agents provides one indication of exposure. If a person’s titer  level is higher than his or her baseline level, then it may be concluded that  the person has been exposed to the agent. In response to the draft report,  HHS stated that the titer should be at least four times higher than baseline  to be considered an exposure. However, HHS did not provide any support  for its assertion, and we could not find any scientific support for picking  this level.
We consider that any titer elevation where that agent is being worked with  in the laboratory requires further detailed investigation. In addition, the  degree of titer elevation that can be considered as definitively diagnostic  needs to be scientifically validated on an agent-by-agent basis. However,  there are issues with using titer levels as an indication of exposure. For  example, determining when the exposure took place is not  straightforward, and methods for determining titers are not standardized  across laboratories.
TAMU has a program to monitor blood serum for those staff working with  C. burnetii. While humans are very susceptible to Q fever, only about one- half of all people infected with C. burnetii show signs of clinical illness.  During the DSAT inspection that was triggered by the uncovering of the  Brucella incident, DSAT came across clinical records showing that several  laboratory workers had elevated titers for C. burnetii. No reports of this  possible exposure had been sent to DSAT. DSAT noted this issue and, on  April 24, 2007, TAMU submitted the required Form 3 to DSAT.
However, as a result of subsequent discussion with the individuals who  had the elevated titers, TAMU officials began to doubt whether the  elevated titers resulted from exposures that had occurred at TAMU. In one  case, TAMU said, one of the infected laboratory workers had only recently  been hired by TAMU but had worked in a clinical laboratory in China  where C. burnetii was known to have been present. It is not clear how the  elevated titer related to the employee’s baseline titer taken at the time of  employment. In another case, the worker claimed to have been exposed  many years earlier and to have always registered high, although the actual  levels varied. DSAT officials disagreed with this interpretation and  believed the high titers resulted from exposures at TAMU.
TAMU officials told us that they initially responded to the uncovering of  the elevated titer incidents by reporting to DSAT any subsequent elevated  titer level identified in its laboratory workers. TAMU also told us that it is  now unsure how to proceed; it has notified DSAT that, in its opinion, an  exposure suggested by an elevated titer should be defined as having  occurred only after clinical symptoms appear in the individual. TAMU has,  therefore, ceased reporting incidents where there are only elevated titers.  In the absence of clarity over the definition of exposure, TAMU officials  have chosen to define it as they see fit.
DSAT officials told us that they disagreed with TAMU’s interpretation.  Reporting exposures only after clinical symptoms develop could have  dangerous consequences for laboratory workers and even the public.  DSAT conducted multiple follow-up inspections to assist TAMU in  becoming compliant with the select agent regulations. In addition, on  January 18, 2008, DSAT and APHIS posted a guidance document on the  analysis of possible exposure incidents. 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.
section_title: Lessons Learned: Barriers to Reporting, Compliance with Regulations Regarding Training, Informing Medical Providers, and Defining Exposure
paragraphs: The common theme in the TAMU incidents was a lack of rigor in applying  fundamental safety and training procedures coupled with a culture that  embodied a reluctance to be open about problems both within the  organization and with the regulator. According to our experts, such  cultural reticence has historically been a factor in many previous incidents  and can be remedied only by appropriate leadership at the highest level of  the organization coupled with robust and continued action by the  regulator.
Barriers to Reporting Need to Be Identified and Overcome  According to the literature and discussions with federal officials and  experts, accidents in laboratories do occur, mostly as a result of human  error due to carelessness, inadequate training, poor judgment, fatigue, or a  combination thereof. In the case of theft, loss, occupational exposure, or  release of a select agent, the laboratory must immediately report certain  information to DSAT or APHIS.
It has been suggested that there is a disincentive to report laboratory- acquired infections and other mishaps at research institutions because it  could result in (1) negative publicity for the institution and the worker or  (2) scrutiny from a granting agency that might lead to a suspension of  research or an adverse effect on future funding.
In order to enhance compliance with reporting requirements, barriers  need to be identified, and targeted strategies need to be applied to remove  those barriers. The literature identifies a number of barriers, including  the lack of explicit standardized protocols;  the lack of effective training on protocols;  the lack of awareness that infection may have been laboratory-acquired;  reporting systems that may have required individuals to pass through  layers to reach the biosafety office (e.g., the supervisor, laboratory  manager, or principal investigator);  fear of punitive measures at the laboratory or institutional level;  individual or institutional embarrassment;    a poor relationship with medical support services (such as occupational  safety and health services); and  the lack of useful investigation/follow-up/feedback.
In addition, these incidents need to be analyzed so that (1) biosafety can  be enhanced by shared learning from mistakes and (2) the public can be  reassured that accidents are thoroughly examined and the consequences  of an accident are contained. One possible mechanism for analysis  discussed in the literature is the reporting system used for aviation  incidents that is administered by the National Transportation Safety Board  and the Federal Aviation Administration. When mistakes are made, they  are analyzed and learned from without being attributed to any one  individual. Although experts have agreed that some form of personal  anonymity would encourage reporting, it is not clear how this mechanism  would be applied to high-containment laboratories where, for example,  one may not know about the exposure or whether the event is significant  enough to be reported.
Compliance with Regulations Regarding Agent- and Experimental  Task-Specific Training Is Needed to Ensure Maximum Protection  The select agent regulations require safety risk assessments whenever  work with select agents is proposed. Risk assessments are of paramount  importance because the investigator, management, and biosafety  representatives must establish guidelines for safe, secure, and efficient  research. Personnel working with select agents need training to ensure  their own safety and that of coworkers and the surrounding community.  Training is specifically designed to address select agent characteristics  that include infectivity and pathogenicity. Training must also address  hazardous operations such as intentional aerosolization, centrifugation,  and homogenization. Some laboratories require inexperienced workers to  be mentored by personnel experienced in containment procedures, a  process that can take up to a year to complete. The mentor maintains a  checklist of important operations that must be performed in a responsible  manner before the worker will be allowed to work independently. Non- laboratory personnel who require access to high-containment laboratories  (inspection, maintenance, and calibration staff) must also receive training  that covers emergency response and agent-specific information.
If TAMU had provided effective, measurable staff training—including  protocol-specific training on agent characteristics for Brucella (infectivity  and pathogenicity), common routes of infection, and medical signs and  symptoms information—the worker might have been more aware of the  dangers involved when cleaning the aerosol chamber and could have been  protected from this exposure. Typical routes of infection differ for M.  tuberculosis and Brucella, and normal procedures, including gowning and  respiratory equipment, vary for the two agents. For example, the  laboratory worker wore protective glasses, but they were not tight fitting.  Experts told us that if procedures that are effective to avoid exposure to  live virulent M. tuberculosis were being followed correctly, these should  have been effective for Brucella despite the difference in the infectious  dose.
According to an expert who has managed high-containment laboratories,  there are risks involved in working alternately in BSL-2 and BSL-3  laboratories with their different levels of procedures and practices.  Laboratory workers may develop a routine with BSL-2 procedures that  may be difficult to consciously break when working with the more  dangerous agents and activities requiring BSL-3 containment. Adequate  training can help to minimize the risks involved.
Standardized Mechanisms for Informing Medical Providers about  the Agents Laboratory Staff Work with Must Be Developed  Severe consequences for the worker can result from delays in  (1) recognizing when an exposure has occurred or (2) medical providers  accurately diagnosing any resulting infection. Further, if the worker  acquires a disease that is easily spread through contact (direct physical  and/or respiratory), there can also be severe consequences for the  surrounding community.
According to the BMBL, the incidents causing most laboratory-acquired  infections are often accidental and unknown. Those involved can conclude  that an exposure took place only after a worker reports illness—with  symptoms suggestive of a disease caused by the relevant agent—some  time later. An infected person may be contagious for weeks until clinical  symptoms become apparent. It is important that exposure be identified as  soon as possible so that proper diagnosis and prompt medical treatment  can be provided. To do so, medical providers need to be informed, in a  standardized way, of all the agents that laboratory staff work with.
The issue of recognizing exposure and infection is not new, and  organizations have put in place systems and procedures that, while not  infallible, greatly facilitate such recognition. As part of the oversight  process, a review and evaluation of such procedures and their  effectiveness are likely to be beneficial.
Current Confusion over the Definition of Exposure Needs to Be  Addressed  According to our experts, a system that requires documentation of all  accidental releases of select agents by whatever means and ensures that  this information is available to the inspecting/oversight authority would  provide both a valuable database and the foundation for any further  investigation. Any accidental release in an area where unprotected  personnel are present should then be considered a de facto exposure and  be immediately reported to the oversight authority whether or not there is  any resulting infection. Laboratory personnel who contract any infection,  even if there is no evidence of exposure, should inform their physician  about their work, including details of the specific agent(s) that they work  with.
When we asked DSAT officials about the confusion over the definition of  an exposure, they agreed that the terms need to be clearly defined and  stated that they were drafting new guidance. DSAT officials noted,  however, that it is unwise to wait until clinical symptoms appear before  determining that an exposure has taken place, as this could potentially  endanger a worker’s life and, in the case of a communicable disease, the  lives of others. A DOD and NIH expert on this issue told us that correctly  interpreting the meaning of elevated titers—whose characteristics can  vary by agent, host, and testing laboratory—is challenging since many  serological testing methods have not been validated.
To help clarify any confusion about what is considered a reportable theft,  loss, or release, CDC released a new guidance document. Scenario 20 in  this document is an attempt to provide a simple approach by identifying  three possible explanations for an elevated titer. However, it fails to go far  enough and should state that an elevated titer of an agent that is being  worked with in the laboratory should be regarded as prima facie evidence  of exposure unless and until proved otherwise. Although clinical samples  should then be taken at once to look for evidence of active infection,  treatment of the person, as appropriate, should begin without delay to  protect the health of the individual and, in some cases, safeguard the  wider community.
Serological testing is an indirect diagnostic tool suggesting, but not  proving, exposure to an agent and is typically used to direct follow-up with  more conclusive tests. Because elevated titers can be due to reasons other  than active infection with a particular agent, the results need to be treated  with caution. Nevertheless, an elevated antibody titer in cases where that  agent is being worked with in the laboratory must always be a matter of  concern and action.
Serological testing is not definitive and scenario 20 does not provide clear  guidance with regard to follow-up actions. Accordingly, standard  operating procedures need to be developed by the institutions working  together with biosafety officers/responsible officials and occupational  health physicians to describe the appropriate course of action when  elevated titers are observed.
The use of serological testing as a method to identify potential exposures  to select agents must be approached with a high degree of caution. First,  guidelines must be very clear regarding the intended use of any serology- based screening program. If routine screening indicates elevated antibody  titers against a specific pathogen over baseline levels, it may suggest a  laboratory exposure to a pathogen; however, alternative explanations are  also feasible. The increase in titers may indicate natural exposure to the  agent (depending on the agent and location of the laboratory). The  increase could also result from inconsistencies associated with laboratory  testing. Most serological assays for select agents are not commonly  conducted in clinical laboratories and are mostly performed in research  laboratories. As such, these assays may not be properly controlled and  validated. Assay-to-assay variation may be high, especially if experience is  limited. Additionally, such assays are not particularly robust unless  baseline specimens are available for comparison testing and serum  samples are collected at relatively short intervals (for example, 3 to 6  months).
Similarly, a serological screening program used as a method to diagnose  infection or prevent the spread of contagious pathogens to the community  is unlikely to be successful unless samples are taken at short intervals, as  elevated antibody titers are usually detected after the period of maximum  contagiousness of most pathogens. Therefore, the most appropriate use  for a serological screening program would be to identify past exposures  and to facilitate remedial training or conduct retrospective risk analyses  that might lead to improved risk mitigation procedures and policies that  might prevent future exposures. It is critical that guidance on the use of  blood screening programs clearly identify the purpose of these programs  and also provide guidance on how information from these programs  should be used. Any suspicion of exposure should be reported and  investigated, and the result of that investigation should be reported, thus  providing a complete picture for DSAT and reducing subjective bias in  reporting.
The development of scientifically sound and standardized methods of  identifying exposure is critical so that individual laboratory owners are not  left to determine for themselves what is and what is not reportable. DSAT  and APHIS could provide specific guidance on exposure benchmarks for  each of the different select agents and toxins.
section_title: Actions Taken by the Regulatory Agency—DSAT— Subsequent to the Incident
paragraphs: On April 20, 2007, DSAT issued a cease-and-desist order suspending work  with Brucella species at TAMU. On June 30, 2007, DSAT suspended all  work with select agents at TAMU. The DSAT concerns included whether  TAMU had a plan to prevent unauthorized access to select agents and  toxins and a program that provided effective medical surveillance of  occupational exposures to select agents and toxins. DSAT conducted a  comprehensive site review and released a report in August 2007 that  detailed a long list of safety violations, including instances in which the  school did not immediately report or neglected to report laboratory  worker infections or exposure to Brucella or C. burnetii. It also extended  the suspension of research with select agents until the university  addressed the issues in the August report.
HHS’s Office of Inspector General (OIG) imposed a fine on TAMU for the  select agent violations. The HHS OIG was delegated authority to impose  civil monetary penalties of up to $250,000 against an individual and up to  $500,000 against any other person, including any entity. 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.
section_title: Incident 3: Power Failures at CDC’s High- Containment Laboratories
paragraphs: Continuity of electrical power is vital for the safe functioning of high- containment laboratories, in particular since maintenance of essential  pressure differentials using electrically driven fans provides an important  barrier for preventing the uncontrolled release of agents. 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.
On June 8, 2007, the CDC campus in Atlanta experienced lightning strikes  in and around its new BSL-4 facility, and both the Georgia Power-supplied  primary power and CDC-supplied backup power from its centrally-located  generator plant were unavailable. 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. 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. With the grounding cable  cut, the lightning strikes caused the circuit breakers in the building’s  switchgear to disengage or open, resulting in a loss of primary power to  the building. In addition, when the circuit breakers disengaged, the CDC’s  backup generators were electrically isolated from the building and could  not supply the building with power. It took approximately an hour for the  CDC facility staff to reset the circuit breakers in the building to reengage  the primary power.
Because of the June 2007 power outage incident, questions about the  design of the backup power system for the new facility resurfaced. When  the CDC designed the backup power system for the new BSL-4 facility, it  decided to use diesel generators centralized at CDC’s utility plant that also  serve other facilities, as well as functions such as chillers, on the campus.  According to internal documents provided to us, during the design phase  for the facility, some CDC engineers had questioned the choice of this  remotely placed, integrated design rather than a simpler design using local  backup generators near the BSL-4 facility.
According to CDC facility officials, the full backup power capabilities for  the new BSL-4 facility were not in place at the time of the power outage  but were awaiting completion of other construction projects on campus.  Once these projects are completed, these officials said, the new BSL-4  facility will have multiple levels of backup power, including the ability to  get power from a second central utility plant on campus, if needed. But  some CDC engineers that we talked with questioned the degree of  complexity in the design. They worried that an overly integrated backup  power system might be more susceptible to failure. As a result of the  power outage, CDC officials conducted a reliability assessment for the  entire campus power system, which included the backup power design for  the new BSL-4 facility. CDC concluded that its existing centrally located  generators and planned power-related construction projects with  equipment upgrades were more reliable and cost-effective than scenarios  that locate generators at individual buildings.
CDC officials reported that its backup power system is tested monthly, as  required by building code. In commenting on our draft report, CDC  provided studies and data that showed the theoretical reliability of the  power system. However, CDC could not provide us documentation of  actual non-testing instances where the backup generator system operated  as designed. This incident highlighted the risks inherent in relying on  standard building codes to ensure the safety of high-containment  laboratories—as there are no building codes and testing procedures  specifically for high-containment laboratories.
In a second incident, on Friday January 4, 2008, CDC officials told us that  nearby construction again damaged the grounding system of the building  containing the new BSL-4 facility. The damage was observed when it  occurred, but the cable was not repaired until the following week. While  there was no loss of power to the BSL-4 facility, the potential for repeating  a grounding-related power failure existed until repairs were made.
According to CDC officials, at the time of both incidents, the new BSL-4  facility in building 18 was in preparation to become fully operational. No  laboratory work of any kind had been conducted inside the BSL-4  laboratories, and no live agents were inside the facility as the  commissioning process was still ongoing and the laboratories were not  activated. However, given that the grounding cables were cut, it is  apparent that the building’s integrity as it related to adjacent construction  was not adequately supervised. Further, according to CDC officials,  standard procedures under building codes do not require monitoring of  the integrity of the electrical grounding of the new BSL-4 facility. CDC has  now instituted annual testing of the electrical grounding system as the  result of its review of these incidents.
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.
subsections: section_title: Lessons Learned: BSL -3 and -4 Laboratory Safety Measures Must Be Commensurate with the Level of Risk These Laboratories Present
paragraphs: In any workplace building—regardless of the nature of its activities—there  are safety features to protect the physical safety of workers. Various  building codes cover many aspects of building design and construction  required to achieve this safety objective, but the codes are subject to local  interpretation. In general, the building codes enable (1) personnel to safely  evacuate and (2) rescue personnel or firefighters to perform their jobs. By  definition, additional hazards beyond those anticipated by standard  building codes potentially exist in high-containment laboratories (BSL-3  and BSL-4), and they are addressed in BMBL. However, according to CDC  and NIH, BMBL is only advisory.
BMBL contains principles and guidelines, but the document does not  provide specific detail on how functional requirements are to be translated  into design solutions. According to our experts, there have been instances  where modifications to laboratories were required after construction to  achieve the necessary compliance. A more active, early, and continuing  dialogue between builders, operators, and regulators may be beneficial in  avoiding such waste and is especially relevant where tax dollars are  committed to the creation or upgrading of high-containment laboratories.
Because BMBL addresses issues relating to maintaining the containment  of biological agents to protect both workers and the wider public, its  guidelines are potentially more restrictive than the building codes.  According to our expert panel, a clear and unambiguous set of standards  stating the various capabilities that are required to maintain the integrity  of all high-containment laboratories is necessary. Such a set of standards  will need to integrate building codes with the BMBL provisions or  amendments thereto. These standards should be national—not subject to  local interpretation—and address the possibility that one or more  emergency or backup systems may fail. Most importantly, any set of  scenarios aimed at maintaining containment integrity must be empirically  evaluated to demonstrate its effectiveness. Adequate oversight of any  nearby activities—such as adjacent construction with its potential to  compromise buried utilities—must also be taken into consideration when  evaluating the safety measures required to manage the risks of high- containment laboratories.
The CDC’s BSL-4 laboratory was designed with multiple layers of  electrical power so that if primary power failed, a secondary source of  power would be in place for continuity of operations. Failure to monitor  the system’s integrity, however, compromised the ability of either power  source to support critical operations. The power outages at CDC  demonstrate a need to create understanding throughout the organization  that effective biosafety involves layers of containment and, furthermore,  that the loss of any one layer is serious even though the remaining layers,  as intended, do maintain containment. Thus, procedures are required to  regularly assess the functional integrity of every layer of containment and  to initiate immediate corrective actions as required. The fact that taken as  a whole, containment is being maintained is not a sufficient measure of  system integrity: each component must be individually assessed and its  operational effectiveness validated on a regular schedule.
section_title: Actions Taken by the Regulatory Agency—DSAT— Subsequent to the Incident
paragraphs: 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.
section_title: Incident 4: Release of Foot-and-Mouth Disease in the United Kingdom
paragraphs: High-containment laboratories are highly sophisticated facilities that  require specialized expertise to design, construct, operate, and maintain.  Because these facilities are intended to contain dangerous  microorganisms, usually in liquid or aerosol form, even minor structural  defects—such as cracks in the wall, leaky pipes, or improper sealing  around doors—could have severe consequences. Supporting  infrastructure, such as drainage and waste treatment systems, must also  be secure.
In August 2007, foot-and-mouth disease contamination was discovered at  several local farms near Pirbright in the U.K., the site of several high- containment laboratories that work with live foot-and-mouth disease virus.  Foot-and-mouth disease is one of the most highly infectious livestock  diseases and can have devastating economic consequences. For example,  a 2001 epidemic in the U.K. cost taxpayers over £3 billion, including some  £1.4 billion paid in compensation for culled animals. Therefore, U.K.  government officials worked quickly to contain and investigate this recent  incident.
subsections: section_title: Lesson Learned: Facilities Supporting High-Containment Laboratories Must Ensure the Operational Effectiveness of Physical Infrastructure
paragraphs: The investigation of the physical infrastructure at the Pirbright site found  evidence of long-term damage and leakage of the drainage system  servicing the site, including cracked and leaky pipes, displaced joints,  debris buildup, and tree root ingress. While the definitive cause of the  release has not been determined, it is suspected that contaminated waste  water from Pirbright’s laboratories leaked into the surrounding soil from  the deteriorated drainage pipes and that live virus was then carried off-site  by vehicles splashed with contaminated mud.
The cracked and leaky pipes found at Pirbright are indicative of poor  maintenance practice at the site. The investigation found that (1)  monitoring and testing for the preventive maintenance of pipe work for  the drainage system was not a regular practice on-site and (2) a  contributing factor might have been a difference of opinion over  responsibilities for maintenance of a key pipe within the drainage system.
High-containment laboratories are expensive to build and expensive to  maintain. Adequate funding for each stage needs to be addressed.  Typically, in large-scale construction projects, funding for initial  construction comes from one source, but funding for ongoing operations  and maintenance comes from another. For example, NIAID recently  funded 13 BSL-3 laboratories as regional biocontainment laboratories  (RBL) and 2 BSL-4 laboratories as national biocontainment laboratories  (NBL). According to NIAID, it contributed to the initial costs for planning,  design, construction, and commissioning and provided funding to support  the operation of these facilities. For these laboratories, the universities are  partially responsible for funding maintenance costs.
The Pirbright incident shows that beyond initial design and construction,  ongoing maintenance plays a critical role in ensuring that high- containment laboratories operate safely and securely over time. Because  even the smallest of defects can affect safety, ensuring the continuing  structural integrity of high-containment laboratories is an essential  recurring activity.
The failure of part of the physical infrastructure at the U.K.’s Pirbright  facility and the outbreak of foot-and-mouth disease highlight the  importance of ongoing maintenance of such facilities, together with clear  lines of responsibility regarding shared infrastructure facilities. In  addition, this incident and other incidents emphasize the importance of  regulators and laboratories working in partnership to either ensure that  funding to maintain the infrastructure is available or alter work programs  and eliminate activities that cannot be performed safely.
section_title: Actions Taken by the U.K. Regulatory Agency Subsequent to the Incident
paragraphs: Since the outbreak of foot-and-mouth disease originating from Pirbright, a  number of regulatory decisions have been made:  1.  The U.K. government undertook a review of the regulatory framework  governing work with animal pathogens that resulted in a November  2007 report. The government accepted all the report’s  recommendations, which included (1) moving regulation of work with  animal pathogens from Defra to HSE and (2) developing a single  regulatory framework covering work with human and animal  pathogens based on the model provided by the Genetically Modified  Organisms (Contained Use) Regulations 2000. This framework adopts  a risk-based approach to regulation. 2.  The Specified Animal Pathogens Order (SAPO) was amended in April  2008 to give inspectors increased powers, including the power to serve  improvement and prohibition notices on entities (called duty holders  in the U.K.) to remedy poor standards in such areas as containment  and management. At the same time, HSE entered into an agency  agreement with Defra to inspect premises where work with SAPO  agents is carried out before Defra issues licenses; the license  conditions are based on recommendations from HSE. Furthermore,  HSE inspectors investigate any accidents and also proactively inspect  facilities to ensure compliance with the license conditions. 3.  Both organizations at Pirbright (Institute for Animal Health (IAH) and  Merial) had their licenses amended or withdrawn following the  outbreak. The IAH license was amended to allow diagnostic work (in  the epidemiology building) and a limited amount of research in the  arbovirology building. No animal work has been licensed to date,  although new animal house facilities are nearing completion, and work  may be licensed later this year.  4.  All the drainage systems on-site have been tested and relined, and a  new dual containment system has been laid to connect laboratories to  a refurbished heat treatment plant. This new system is not yet  operational, although it is in the final stages of commissioning. In the  meantime, no laboratory or manufacturing effluent is discharged to the  relined drainage system unless it has been heat treated by autoclaving  (IAH) or been through a validated heat treatment cycle (Merial). The  only effluent going to the drain and to the final chemical treatment  plant is shower water, which should not contain virus as all activities  are carried out in cabinets or in enclosed systems. 5.  A newly refurbished building on the IAH has recently been licensed to  allow small scale research on a number of SAPO 4 viruses. 6.  Merial was fully relicensed following amendments to its procedures  and joint Defra and HSE inspections. The new licenses are more  detailed than the original versions and impose many more license  conditions on the company. 7.  No enforcement action has been taken against either organization  following the outbreak of foot and mouth disease. The enforcing body  (part of the local council) decided that there was insufficient evidence  to prosecute either IAH or Merial.
section_title: Conclusions
paragraphs: High-containment laboratories provide facilities that are needed for basic  research, development of detection technologies, and diagnostic and  medical countermeasures for biothreats. Accordingly, facilities are  specialized and cannot easily be converted from one function to another.  Medium- to long-term advance planning for the appropriate capacity levels  is therefore essential, as is knowledge of existing capacity. Such advance  planning needs to take into account the (1) projected future balance  between biodefense and more traditional public health work, (2) the  specific infectious disease problems and targets that the expansion is  meant to address, and (3) targets for the laboratory expansion’s timetable  or benchmarks as to when specific capacities need to be available. We  were unable to identify any governmentwide strategic evaluation of these  issues for high-containment laboratories.
Furthermore, since no single agency is in charge of the current expansion,  no one is determining the associated aggregate risks posed by the  expansion. As a consequence, no federal agency can determine whether  high-containment laboratory capacity may now be less than, meet, or  exceed the national need or is at a level that can be operated safely.
If an agency were tasked or a mechanism were established with the  purpose of overseeing the expansion of high-containment laboratories, it  could develop a strategic plan to (1) ensure that the number and  capabilities of potentially dangerous high-containment laboratories are no  greater or less than necessary, (2) balance the risks and benefits of  expanding such laboratories, and (3) determine the type of oversight  needed.
Such an agency or mechanism could analyze the biothreat problems that  need to be addressed by additional BSL-3 and -4 laboratories, the scientific  and technical capabilities and containment features that such laboratories  need to have, how the laboratories should be distributed geographically,  and how the activities of the laboratories would be coordinated to achieve  intended goals.
Standards for several key issues have not been developed. The agency or  mechanism responsible for overseeing the expansion of high-containment  laboratories could also be responsible for coordinating with the scientific  community to develop guidelines for high-containment laboratory design,  construction, and commissioning and training standards for laboratory  workers; providing definitions for exposure; developing appropriate  inventory control measures; and providing guidance on the most efficient  approach to personnel reliability programs.
The oversight agency or mechanism could also address issues related to  the ongoing funding needs of high-containment laboratories. While NIAID  has provided funding to build RBLs and NBLs, these laboratories are  expected to compete for funding from NIH to sustain their research. It is  unclear what will happen to these facilities, their trained personnel, and  their technology if no such funding is available. Further, as these facilities  and other high-containment laboratories age, adequate funding sources  must be identified for upgrades and maintenance, or the risks that they  pose may outweigh their benefits.
Once laboratories have been commissioned and begin operating,  continuing maintenance and testing/validation programs are needed to  ensure that operating standards and regulatory compliance are  maintained. As facilities age, the costs of such programs will rise and are  likely to consume an increasing proportion of budgets. Although this  affects federal, industrial, and academic laboratories, the impact is likely  to be greatest on academic laboratories. Although federal laboratories are  subject to annual funding, they tend to have programs that have long-term  commitments and are not usually subject to major changes even if  principal investigators (scientists) relocate. Industrial laboratories exhibit  similar stability of operations once they are committed to projects and  programs. In all these cases, maintenance budgets are less tied to funding  for research than are those of academic laboratories, which are highly  dependent on research grant funding to support both infrastructure  maintenance as well as research programs. Indeed, the two activities may  compete for available money. Relocation of a principal investigator who is  the recipient of research grant funding can create problems for the  institute in maintaining the laboratory facilities. Given the high costs of  creating high-containment laboratories, consideration also needs to be  given to the issue of their maintenance and support as distinct from  funding for research activity.
The four incidents at USAMRIID, TAMU, CDC, and Pirbright exemplify a  number of failures of systems and procedures that are meant, in  combination, to maintain the biosafety of high-containment laboratories to  protect laboratory workers and the public. DSAT and APHIS could  examine these incidents and apply the lessons learned across the program.
These incidents have been described and analyzed in detail both because  they are recent and because detailed information was available about the  various factors involved. Unfortunately, the incidents and their causal  factors are not unique, and the scientific literature contains information  about many incidents occurring over decades that often involved similar  factors and the failure to maintain adequate biosafety.
Overall, the safety record of high-containment laboratories has been good,  although a number of weaknesses have become apparent over time.  Consequently, along with expansion there needs to be a commensurate  development of both operational and oversight procedures to address  known deficiencies and, as far as practicable, proactively evaluate future  risks.
Laboratory operators, in collaboration with regulators, need to develop  and work through potential failure scenarios and use that information to  develop and put in place mechanisms to challenge procedures, systems,  and equipment to ensure continuing effectiveness.
section_title: Recommendations for Executive Action
paragraphs: 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  the number, location, and mission of the laboratories needed to effectively  meet national goals to counter biothreats;  the existing capacity within the United States;  the aggregate risks associated with the laboratories’ expansion; and  the type of oversight needed  and (2) develop, in consultation with the scientific community, national  standards for the design, construction, commissioning, and operation of  high-containment laboratories, specifically including provisions for long- term maintenance.
We recommend that the Secretaries of HHS and USDA develop (1) a clear  definition of exposure to select agents and (2) a mechanism for sharing  lessons learned from reported laboratory accidents so that best  practices—for other operators of high-containment laboratories—can be  identified.
Should the Secretaries consider implementing a personnel reliability  program for high-containment laboratories to deal with insider risk, we  recommend that they evaluate and document the cost and impact of such  a program.
Recognizing that biological agent inventories cannot be completely  controlled at present, we also recommend that the Secretaries of HHS and  USDA review existing inventory control systems and invest in and develop  appropriate technologies to minimize the potential for insider misuse of  biological agents.
section_title: Agency Comments and Our Evaluations
paragraphs: We obtained written comments on a draft of our report from the  Secretaries of HHS and USDA. The Executive Office of the President:  National Security Council did not provide comments. HHS and USDA  concurred with our recommendations that were directed to them (see  appendixes VII and VIII). HHS officials also provided general comments,  including some concerns that are discussed in appendix VII. In addition,  DOD, HHS, and USDA officials provided technical comments, which have  been addressed in the body of our report, as appropriate.
We are sending copies of this report to the Executive Office of the  President; the Attorney General; and the Secretaries of Agriculture,  Defense, Health and Human Services, and Homeland Security. In addition,  the report will be available at no charge on the GAO Web site at  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.
section_title: Appendix I: Scope and Methodology
paragraphs: To determine the extent of expansion in the number of high-containment  laboratories and the areas experiencing growth, we interviewed agency  officials and experts and reviewed documents provided by agencies and  scientific literature. To determine which federal agency has the mission to  track and determine the aggregate risks associated with the proliferation  of BSL-3 and BSL-4 laboratories in the United States, we surveyed 12  federal agencies that are involved with these laboratories in some  capacity—for example, research, oversight, or monitoring.
The survey requested information on whether the agency (1) has a mission  to track the number of high-containment laboratories, (2) has a need to  know the number of operating BSL-3 and BSL-4 laboratories, and   (3) knows that number. The agencies that received our survey included  the Department of Agriculture; the Department of Commerce; the  Department of Defense; the Department of Energy; the Environmental  Protection Agency; the Department of Health and Human Services,  including the Centers for Disease Control and Prevention (CDC); the  Department of Homeland Security; the Department of the Interior; the  Department of Justice, including the Federal Bureau of Investigation; the  Department of Labor, including the Occupational Safety and Health  Administration; the Department of State; and the Department of Veterans  Affairs. In addition, we sent our survey to intelligence agencies, including  the Central Intelligence Agency, the National Counter-Terrorism Center,  the Defense Intelligence Agency, and the Office of Intelligence Analysis  within DHS.
To supplement existing information on the current number of BSL-3 and  BSL-4 laboratories in the United States, we surveyed 724 individuals, who  were identified through various open sources as knowledgeable contacts  on biosafety laboratories, through a self-administered electronic  questionnaire posted on the World Wide Web between April 2007 and May  2007. We obtained responses from 295 respondents, for an overall  response rate of 41 percent. Several important limitations should be noted  about our survey. First, the universe of BSL-3 and -4 laboratories is  unknown. While we used multiple sources to develop our list of potential  respondents, there are likely other laboratories that we were unable to  identify. Second, there may be duplicate responses in cases where  multiple persons responded to the survey for a single institution. The data  from our questionnaire are sufficiently reliable to demonstrate that there  are BSL-3 or -4 laboratories that do not work with select agents.
We also met with officials of the Division of Select Agents and Toxins and  the Animal and Plant Health Inspection Service to gain additional  information about the expansion of high-containment laboratories. Finally,  we reviewed documents these agencies provided, including pertinent  legislation, regulations, and guidance, and reviewed scientific literature on  risks associated with high-containment laboratories.
To develop lessons learned from recent incidents at four high-containment  laboratories, we interviewed academic experts in microbiological research  involving human, animal, and plant pathogens and conducted site visits at  selected federal, civilian, military, academic, and commercial BSL-3 and  BSL-4 laboratories, including the sites involved in the recent incidents.  Specifically, we conducted site visits at CDC and Texas A&M University  (TAMU); talked to United Kingdom officials at the Health Safety Executive  and the Department for Environment, Food, and Rural Affairs; and  reviewed documents and inspection reports.
To discuss the incidents at TAMU and CDC, we conducted site visits and  interviewed the relevant officials. During our site visit to CDC, we  interviewed relevant officials, including the officials of CUH2A, Inc.—the  contractor who designed the backup power system for the new BSL-4  laboratory in Atlanta—as well as the expert hired by this firm to conduct  the reliability study for the backup power system.
We conducted our work from September 2005 through June 2009 in  accordance with generally accepted government auditing standards. Those  standards require that we plan and perform the audit to obtain sufficient,  appropriate evidence to provide a reasonable basis for our findings and  conclusions based on our audit objectives. We believe that the evidence  obtained provides a reasonable basis for our findings and conclusions  based on our audit objectives.
section_title: Appendix II: Expert Panel
paragraphs: 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.
section_title: Appendix III: List of Select Agents and Toxins as of November 17, 2008
paragraphs: 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   Ricin  Rickettsia prowazekii  Rickettsia rickettsii  Saxitoxin  Shiga-like ribosome inactivating proteins  Shigatoxin  South American Haemorrhagic Fever viruses  Flexal  Guanarito  Junin  Machupo  Sabia  Tetrodotoxin  Tick-borne encephalitis complex (flavi) viruses  Central European Tick-borne encephalitis  Far Eastern Tick-borne encephalitis  Kyasanur Forest disease  Omsk Hemorrhagic Fever  Russian Spring and Summer encephalitis  Variola major virus (Smallpox virus) and      Variola minor virus (Alastrim)  Yersinia pestis USDA Select Agents and Toxins  African horse sickness virus  African swine fever virus  Akabane virus  Avian influenza virus (highly pathogenic)  Bluetongue virus (exotic)  Bovine spongiform encephalopathy  Camel pox virus  Classical swine fever virus  Ehrlichia ruminantium (Heartwater)  Foot-and-mouth disease virus  Goat pox virus  Japanese encephalitis virus  Lumpy skin disease virus  Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1)  Menangle virus  Mycoplasma capricolum subspecies capripneumoniae (contagious  caprine pleuropneumonia)
Mycoplasma mycoides subspecies mycoides small colony (MmmSC)  (contagious bovine pleuropneumonia)
Peste des petits ruminants virus  Rinderpest virus  Sheep pox virus  Swine vesicular disease virus  Vesicular stomatitis virus (exotic): Indiana subtypes VSV-IN2, VSV-IN3  Virulent Newcastle disease virus  Overlap Select Agents and Toxins  Bacillus anthracis  Brucella abortus  Brucella melitensis  Brucella suis  Burkholderia mallei (formerly Pseudomonas mallei)  Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)  Hendra virus  Nipah virus  Rift Valley fever virus  Venezuelan Equine Encephalitis virus USDA Plant Protection and Quarantine (PPQ) Select Agents and  Toxins  Peronosclerospora philippinensis (Peronosclerospora sacchari)  Phoma glycinicola (formerly Pyrenochaeta glycines)  Ralstonia solanacearum race 3, biovar 2  Schlerophthora rayssiae var zeae  Synchytrium endobioticum  Xanthomonas oryzae pv. Oryzicola  Xylella fastidiosa (citrus variegated chlorosis strain)
section_title: Appendix IV: Biological Agents Recommended for BSL-3 Containment That Are Not Select Agents
paragraphs: There are a number of biological agents causing severe illness or death  that are not select agents. Some non-select-agents are recommended for  work, research, and production safely under BSL-2 containment (BMBL,  5th Edition). These agents are listed in table 11. Several of these non- select-agents may require BSL-3 containment for specific reasons,  including production of aerosols or large-scale production of these  organisms (BMBL, 5th Edition). These agents are listed in table 12.
section_title: Appendix V: The Army’s Requirements for High-Containment Laboratories in 2001
paragraphs: According to DOD officials, DOD did not have a policy document specific  to biological select agents and toxins (BSAT) or high-containment  laboratories in 2001.
In 2001, all U.S. Army high-containment laboratories working with select  agents were registered with CDC (under 42 C.F.R. § 72.6). Army safety  regulations in place at that time required the following:  1.  A hazard analysis must be conducted to determine safety precautions,  necessary personnel protection, engineering features, and procedures to  prevent exposure for all agents. The Army utilized the risk analysis  technique of maximum credible events, which examines the consequences  of realistic worst-case scenarios. 2.  Facilities must have standard operating procedures, training and  proficiency requirements, medical surveillance, emergency preparedness  procedures (including advance notification to local, state, regional, and  federal emergency response personnel), hazard labeling, disposal and  maintenance controls, and protective equipment for all work with agents. 3.  Quarterly inspections for biosafety level (BSL)-1 and BSL-2 laboratories  and monthly inspections for BSL-3 and BSL-4 laboratories must be  conducted. 4.  All mishaps must be reported and investigated. Medical surveillance of all  workers present must begin immediately after a mishap. 5.  Access control procedures were required to keep people not needed to  operate biological laboratories from entering. 6.  Federal, state, and local laws must be obeyed when transporting agents.  7.  Components that contract out biological defense work must prepare  written procedures that set guidelines for facilities, safety, inspections, and  risk analysis. They were also required to monitor contractor performance  in meeting safety requirements, which includes pre-award inspections,  annual inspections of BSL-3 facilities and semiannual inspections of BSL-4  facilities, documentation of safety training programs, designation of an  individual responsible for safety, and storage and disposal procedures.  Contractors working at BSL-3 and BSL-4 facilities must prepare a plan for  controlling laboratory mishaps.  8.  Facilities must have published safety plans and monitoring procedures that  they coordinated with federal, state, and local emergency services and  practiced with emergency groups. An occupational health program,  including medical surveillance examinations, was also required. 9.  The regulations also set out operational requirements, including laboratory  techniques, based on biosafety level, and emergency procedures, such as  establishing evacuation procedures and an emergency alarm system. 10. Facilities must abide by personal protective equipment requirements  (based on biosafety level), decontamination and disposal requirements and  shipping restrictions, and facility specifications based on biosafety level  and engineering controls.
These regulations are located at 32 C.F.R., parts 626 and 627. Army  pamphlet 385-69 also prescribes the minimum safety criteria and technical  requirements and is used in conjunction with these regulations.  Additionally, since USAMRIID was designated a “restricted area” in 1995, a  National Agency Check was also required for general unescorted access  for all staff. The USAMRIID Special Immunizations Clinic provided  baseline medical and occupational health evaluations of fitness to work in  the laboratories and provided vaccines. Annual medical interviews,  physical exams, and laboratory reassessments were conducted for changes  in health, medication, and duties.
According to information provided to us by USAMRIID, security clearance  was not and is not required to work in high-containment laboratories, and  having a security clearance did not by itself allow access to high- containment laboratories. In 2001, there was no centralized requirement  for inventory control and accountability. Individual scientists maintained  their own stocks and accountability.
CDC’s regulations in 2001 (42 C.F.R. § 72.6) focused on the transfer of  select agents and thus did not focus on personnel security or insider risk  or inventory control of select agents. While Army regulations required that  the consequences of realistic worst case scenarios be examined, insider  risk was not considered in such examinations.
section_title: Appendix VI: CDC’s Integrated Approach to Biocontainment at High-Containment Laboratories
paragraphs: In commenting on the draft report, HHS officials stressed the importance  of the Centers for Disease Control and Prevention’s (CDC) integrated  “three-legged approach” to biocontainment at high containment  laboratories.  They provided the following technical details of their  biocontainment experiences.      “According to CDC officials, monitoring one-pass directional airflow  through negatively pressurized containment zones, enclosed and  separated by airtight doors and structure, with HEPA filtration on both the  supply side (one HEPA filter) and the exhaust side (two HEPA filters),  along with robust Operations and Maintenance protocols (O&M) provides  a sound facility design and construction component for CDC’s ‘three- legged’ approach to biocontainment.  This approach, which is described in  Section II of the BMBL, stresses that laboratory practice and technique is  the most important element of a comprehensive  containment strategy, in  conjunction with appropriate safety equipment (as a primary barrier) and  facilities design/construction and engineering  (as a secondary  containment barrier). CDC maintains that while directional airflow and  negative pressure in BSL-4 laboratories is a critical engineering  component of a normal ‘safe’ operating environment, engineering systems  do fail from time-to-time, for various reasons.    “In the event of a loss of power to the supply and exhaust fans and  controls that maintain negative pressure conditions in CDC’s BSL-4  laboratories, the laboratories go to a ‘static pressure’ status, whereby  secondary containment is maintained by the airtight door gaskets, airtight  construction of interior walls, floors, and ceiling within the BSL-4  laboratory block, and because the HEPA filters on the supply side  and  exhaust ducts are functionally impermeable to air for certain periods of  time under static pressure conditions. In effect proper design,  construction and O&M render the CDC BSL-4 laboratories into airtight  boxes during a complete loss of normal and standby power during these  events.  Containment was also preserved because CDC’s laboratorians are  properly trained in safe laboratory practices and procedures, and BSL  equipment and safety protocols (primary barriers) functioned as intended.   Equipment within the BSL-4 laboratories include biological safety  cabinets, centrifuges, and heavy-duty personal protective suits (i.e., ‘space  suits’).   “In the lightning and bird strike incidents outlined above ,  secondary engineering controls failed due to temporary construction- related impacts, rather than typical operations conditions, and all but UPS- generated life safety required power was lost in B  18. However,  because CDC had appropriated and effective laboratory practice and  safety equipment and practices in place, and because a static pressure  condition had been maintained (as a secondary barrier), the chance of an  accidental release of dangerous pathogens into the environment so as to  cause a significant risk to CDC workers or the surrounding community did  not exist.    “According to CDC officials, the lightning and bird strike incidents are not  typical of O&M-related incidents that CDC has experienced over the years  since they are directly related to the intense construction activities at the  Roybal Campus that have been ongoing since approximately 2000, and are  expected to largely conclude in approximately 2011. The construction  activities are the execution of the Agency’s 10-Year Master Plan to replace  the many 50-year old buildings, including laboratories and infrastructure  at the Roybal and Chamblee Campuses.  CDC date  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.”
section_title: Appendix VII: Comments from the Department of Health and Human Services
paragraphs: The following are GAO’s responses to the Department of Health and  Human Service’s (HHS) comments in a letter dated July 20, 2009.
subsections: section_title: GAO Comments
paragraphs: 1.  We agree with HHS. Our report acknowledges that no executive or  legislative mandate currently requires any agency to gather this  information and we are making a recommendation in this regard. 2.  We agree that instituting new regulatory reporting requirements about  the location of all BSL-3 laboratories could create a burden on private  sector laboratories and would require new federal resources.    3.  Our report did acknowledge information from CDC officials stating  that at the time of both incidents, the new BSL-4 facility was not fully  operational and that no agents were inside the facility. However, we  believe that CDC is missing the point. Given that grounding cables  were cut, it is apparent that the building’s integrity as it related to  adjacent construction was not adequately supervised.  CDC officials  stated that standard procedures under building codes did not require  monitoring of the integrity of the new BSL-4 facility’s electrical  grounding.  This incident highlighted the risks inherent in relying on  standard building codes to ensure the safety of high-containment  laboratories—as there are no building codes and testing procedures  specifically for those laboratories.  We agree with CDC that high- containment laboratories include a three-legged and multi-tiered  approach to containment. However, to have a fully safe system of  containment, any failure of one tier or one of the legs needs to be  rapidly identified and corrected. Our focus in this incident was on  CDC’s power system and lessons that can be learned for other high- containment labs. 4.  We modified the language in our report to note that a loss of power  could have serious consequences under certain circumstances. 5.  While we agree that critical differences, purposes, and functions  differentiating code-required emergency power and legally required  standby power are important when planning and designing electrical  distribution systems for biological laboratories and other science  buildings, this does not materially affect our findings. 6.  We disagree with CDC that the titer should be at least four times higher  than the baseline level to be considered an exposure.  Most  importantly, any increase in titers involving an agent that is being  worked on at a laboratory should be taken seriously and investigated.
The laboratory safety aspect of antibody titers is clearly different from  those that apply to a general clinical situation.  The increase in titers  may indicate natural exposure to the agent (depending on the agent  and location of the lab) or result from inconsistencies associated with  laboratory testing.  Most serological assays for select agents are not  commonly conducted in clinical laboratories and are primarily  performed in research laboratories.  As such, these assays may not be  properly controlled and validated.  Assay-to-assay variation may be  high, especially if experience is limited.  Additionally, such assays are  not particularly robust unless baseline specimens are available for  comparison testing and serum samples are collected within relatively  short time frames (for example, 3 to 6 months).   7.  We agree with HHS that national goals may change over time.
Therefore, it is important that the strategic evaluation of high- containment laboratories be undertaken periodically.  We have  modified our recommendation to include periodic evaluation. 8.  Our report recommends that a single entity be charged with  governmentwide strategic evaluation of high-containment laboratories.  While we agree that there are several challenges, having a single  agency would facilitate a coordinated response. 9.  We agree that future evaluations of laboratory capacity and supply  should examine the needs of the clinical laboratories related to their  high-containment capacity.  However, knowing the number of  laboratories is a key requirement to making such evaluation effective. 10. We disagree. We believe that national standards contribute to ensuring  that all high-containment laboratories meet minimum standards.   National standards are valuable not only in relation to new laboratory  construction but also in ensuring compliance for periodic upgrades.   We agree that BMBL provides guidance on design and construction;  however, the guidance does not provide standards that must be  adhered to.  While sharing lessons learned can be beneficial to meeting  standards, it is not an adequate substitute for the standards themselves.   If existing laboratories do not meet national standards, we believe that  these laboratories need to be brought into compliance.
section_title: Appendix VIII: Comments from the Department of Agriculture
section_title: Appendix IX: GAO Contact and Staff Acknowledgments
subsections: section_title: Staff Acknowledgments
paragraphs: 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.
section_title: Related GAO Products
paragraphs: 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.