E9

UNITED STATES HIGH-CONTAINMENT BIOLOGICAL LABS AND REGULATIONS

United States National Research Council Staff

1.   What high-containment biological research facilities exist in the United States?

Since 2001, the number of facilities that can conduct high-containment biological research (United States Centers for Disease Control [CDC] and Prevention Biological Safety 3 or 4 level—BSL 3-4) in the United States has increased and is expected to continue increasing in the immediate future as planned labs are completed and become operational (United States GAO, 2009a).

A rough estimate of the number of BSL-3 labs can be based on the number of labs registered with the Select Agent Program, the main regulatory program for United States high-risk biological research, which is described in the next section. As of 2010, 1,495 laboratories were registered with the Select Agent Program through the CDC (Kaiser, 2011). This provides only a rough estimate of the number of BSL-3 labs as some select agents can be handled at the BSL-2 level, while some pathogens that necessitate BSL-3 precautions are not select agents.1 Also, some laboratories registered with the Select Agent Program reside outside of the United States.

In 2011, 6 United States entities collectively contained 8 laboratories operating at the BSL-4 level (Table E9-1). Six other BSL-4 laboratories were in the planning or construction phase, one of which will replace an existing laboratory (Table E9-2). BSL-4 facilities, such as the National Institutes of Health’s (NIH) small BSL-4 lab in Bethesda, Maryland, that currently operate only at a lower containment level (United States GAO, 2007) were not included in those totals.

Table E9-1 Operational BSL-4 Labs in the United States.

Laboratory Location
National Institute of Allergy and Infectious Diseases (NIAID) Rocky Mountain Lab Hamilton, MT
Texas Biomedical Research Institute1 San Antonio, TX
University of Texas Medical Branch: Robert E Shope Lab and Galveston National Laboratory Galveston, TX
Georgia State University Atlanta, GA
CDC Special Pathogens Branch: Building 15 and Building 18 Atlanta, GA
United States Army Medical Research Institute for Infectious Diseases (USAMRIID) Fort Detrick, MD

1 Formerly Southwest Foundation for Biomedical Research

SOURCE: Kaiser, 2011; United States GAO, 2009a

Table E9-2 Planned BSL-4 Labs in the United States That Were not Operational as of September 2011.

Laboratory Location
NIAID Integrated Research Facility Fort Detrick, MD
National Biodefense Analysis & Countermeasures Center Fort Detrick, MD
USAMRIID Recapitalizationa Fort Detrick, MD
Boston University National Emerging Infectious Diseases Laboratories (NEIDL)b Boston, MA
Virginia Division of Consolidated Laboratoriesc Richmond, VA
National Bio- and Agro-Defense Facility Manhattan, KS

SOURCE: Kaiser, 2011.

aThis lab will replace the existing USAMRIID facility, which will be decommissioned.

bFor more information see: http://www.bu.edu/dbin/neidl/en/. Accessed October 6, 2011.

cThe Virginia DCLS facility will be built according to BSL-4 specifications, but due to lack of funding for personnel, will likely operate as a BSL-3+. See: http://vaperforms.virginia.gov/agencylevel/stratplan/spReport.cfm?AgencyCode=194. Accessed October 6, 2011.

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1 For a list of Select Agent Pathogens, see: http://www.selectagents.gov/resources/List%20of%20Select%20Agents%20and%20Toxins_111708.pdf. Accessed October 6, 2011.



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E9 UNITED STATES HIGH-CONTAINMENT BIOLOGICAL LABS AND REGULATIONS United States National Research Council Staff 1. What high-containment biological research facilities exist in the United States? Since 2001, the number of facilities that can conduct high-containment biological research (United States Centers for Disease Control [CDC] and Prevention Biological Safety 3 or 4 level—BSL 3-4) in the United States has increased and is expected to continue increasing in the immediate future as planned labs are completed and become operational (United States GAO, 2009a). A rough estimate of the number of BSL-3 labs can be based on the number of labs registered with the Select Agent Program, the main regulatory program for United States high-risk biological research, which is described in the next section. As of 2010, 1,495 laboratories were registered with the Select Agent Program through the CDC (Kaiser, 2011). This provides only a rough estimate of the number of BSL-3 labs as some select agents can be handled at the BSL-2 level, while some pathogens that necessitate BSL-3 precautions are not select agents.1 Also, some laboratories registered with the Select Agent Program reside outside of the United States. In 2011, 6 United States entities collectively contained 8 laboratories operating at the BSL-4 level (Table E9-1). Six other BSL-4 laboratories were in the planning or construction phase, one of which will replace an existing laboratory (Table E9-2). BSL-4 facilities, such as the National Institutes of Health’s (NIH) small BSL-4 lab in Bethesda, Maryland, that currently operate only at a lower containment level (United States GAO, 2007) were not included in those totals. Table E9-1 Operational BSL-4 Labs in the United States. Laboratory Location National Institute of Allergy and Infectious Diseases (NIAID) Rocky Mountain Lab Hamilton, MT Texas Biomedical Research Institute1 San Antonio, TX University of Texas Medical Branch: Robert E Shope Lab and Galveston National Laboratory Galveston, TX Georgia State University Atlanta, GA CDC Special Pathogens Branch: Building 15 and Building 18 Atlanta, GA United States Army Medical Research Institute for Infectious Diseases (USAMRIID) Fort Detrick, MD 1 Formerly Southwest Foundation for Biomedical Research SOURCE: Kaiser, 2011; United States GAO, 2009a Table E9-2 Planned BSL-4 Labs in the United States That Were not Operational as of September 2011. Laboratory Location NIAID Integrated Research Facility Fort Detrick, MD National Biodefense Analysis & Countermeasures Center Fort Detrick, MD USAMRIID Recapitalizationa Fort Detrick, MD Boston University National Emerging Infectious Diseases Laboratories (NEIDL)b Boston, MA Virginia Division of Consolidated Laboratoriesc Richmond, VA National Bio- and Agro-Defense Facility Manhattan, KS SOURCE: Kaiser, 2011. a This lab will replace the existing USAMRIID facility, which will be decommissioned. b For more information see: http://www.bu.edu/dbin/neidl/en/. Accessed October 6, 2011. c The Virginia DCLS facility will be built according to BSL-4 specifications, but due to lack of funding for personnel, will likely operate as a BSL-3+. See: http://vaperforms.virginia.gov/agencylevel/stratplan/spReport.cfm?AgencyCode=194. Accessed October 6, 2011. 1 For a list of Select Agent Pathogens, see: http://www.selectagents.gov/resources/List%20of%20Select%20Agents%20and%20Toxins_111708.pdf . Accessed October 6, 2011. 193

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194 Biosecurity Challenges Private companies, non-profits, academic institutions as well as state, local, and federal agencies maintain high-containment facilities. The Department of Defense (DOD), the Department of Homeland Security (DHS), and the Department of Health and Human Services (HHS) operate the main government facilities, sometimes through contracts with private organizations. DOD operates the United States Army Medical Research Institute for Infectious Diseases (USAMRIID).2 DHS operates the new National Biodefense Analysis and Countermeasures Center (NBACC) through a contract with Battelle National Biodefense Institute and maintains the Plum Island Animal Disease Center, which is scheduled to be replaced eventually by the National Bio and Agro-Defense Facility (NBAF) in Manhattan, Kansas.3 HHS funds multiple BSL-3 facilities at the NIH and BSL-4 facilities at the CDC. In addition, HHS, through the National Institute of Allergy and Infectious Diseases (NIAID), partially funded construction of the Galveston and Boston University National Laboratories (BSL-4) and 13 BSL-3 Regional Biocontainment Laboratories (Table E9-3).4 These laboratories are distributed across the United States to conduct research and assist with public health efforts during emergencies. Additionally, HHS funds the Laboratory Response Network (LRN) that includes over 140 Reference Laboratories that have BSL-3 capabilities and can perform confirmatory testing.5 LRN Reference Laboratories include state and local public health labs as well as military, federal, and international (i.e., Canada, Australia, and United Kingdom) facilities. Table E9-3 Regional Biocontainment Laboratories (RBL). Laboratory Location Tufts Regional Biosafety Laboratory North Grafton, MA Regional Biocontainment Laboratory at Biomedical Science Tower 3 Pittsburgh, PA Center for Predictive Medicine Louisville, KY Colorado State University Regional Biocontainment Laboratory Ft. Collins, CO George Mason University RBL Manassas, VA Global Health Research Building Durham, NC Howard T Ricketts Laboratory RBL Chicago, Il Pacific RBL (under construction) Honolulu, HI Southeast Biosafety Laboratory Birmingham, AL Tulane National Primate Research Center Covington, LA University of Missouri- Columbia RBL Columbia, MO University of Tennessee RBL Memphis, TN New Jersey Medical School Center for Infectious Disease Research RBL Newark, NJ SOURCE: Kaiser, 2011 and http://www.niaid.nih.gov/LabsAndResources/resources/dmid/NBL_RBL/Pages/site.aspx. Accessed October 6, 2011. 2. What government organizations in the United States are responsible for oversight, safety, and security of high-containment biological (high BSL) laboratories? No single government entity has total responsibility for the safety and security of high- containment laboratories (United States GAO, 2007; see page 4). Instead, oversight is provided by multiple organizations under a number of regulatory frameworks, including: 2 To learn more about USAMRIID, see: http://www.usamriid.army.mil/. Accessed October 6, 2011. 3 To learn more about NBACC see: http://www.bnbi.org/. To learn more about NBAF see: http:// www.dhs.gov/nbaf. Accessed October 8, 2011. 4 Available at: http://www.niaid.nih.gov/LabsAndResources/resources/dmid/NBL_RBL/Pages/site.aspx. Accessed October 6, 2011. 5 See: http://www.bt.cdc.gov/lrn/pdf/lrn-overview-presentation.pdf. Accessed October 6, 2011.

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195 Appendix E: Country and Region Overviews Select Agent Program One of the major regulatory programs for high-containment labs in the United States is the Select Agent Program. The program was established in 1996 via the Antiterrorism and Effective Death Penalty Act (P.L. 104-132).1 This law required the Department of Health and Human Services (HHS) to identify a set of organisms and toxins (“Select Agents”) that could be used for bioterrorist attacks and to regulate the transport of those pathogens. Later, the 2001 Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act (USA PATRIOT Act: P.L. 107-56) and the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (P.L. 107-188) added restrictions on the possession, use, and transfer of select agent pathogens and toxins. More information on the history of the Select Agent Program may be found in the National Research Council report on Responsible Research with Biological Select Agents and Toxins (NRC, 2009). The current Select Agent Program covers two lists of pathogens and toxins. The agents on the HHS list are human health threats while those on the United States Department of Agriculture (USDA) list are animal and plant pathogens. Some agents are on both the HHS and USDA lists (overlap agents). The listed agents are to be reviewed every two years. The program also addresses two other areas— people who have access to select agents and facilities where select agents are used. Additionally, the program monitors the quantity of each agent held by each person at each facility. Scientists who conduct research with pathogens on the select agent list must undergo a background check called a Security Risk Assessment (SRA) with the Department of Justice (DOJ). These clearances are pathogen and institution specific, nontransferable, and valid for three years.2 (Prior to June 1, 2011, clearances were valid for five years.) Facilities that possess or use select agents must develop and implement a security plan to protect the select agents from theft or improper access and identify a Responsible Official (RO). The RO has the authority and responsibility to ensure compliance with the regulations and report any incidents to the proper authorities.3 Depending on the pathogen, security plans are submitted either to CDC, USDA’s Animal and Plant Health Inspection Service (APHIS), or both for overlap pathogens. A plan must include a site-specific risk assessment, an agent-specific risk assessment, a threat assessment, a vulnerability assessment, and information about physical security, inventory control, and information systems control.4 CDC and APHIS conduct routine inspections every three years (annually for BSL-4 labs) and may conduct additional inspections at any time if an entity requests a change to its registration.5 During inspections, both APHIS and CDC use standardized checklists to ensure compliance.6 Any problems found during an inspection are reported to the institution and must be addressed. If, for example, CDC finds significant problems at a laboratory the following actions may be taken: “Administrative actions: CDC can decide to suspend or revoke a registered entity’s certificate of registration (a suspension can be for all work at a registered entity or be specific to particular agents or particular types of experiments). Also, CDC can deny an entity’s application to possess, use, or transfer select agents; Referral to HHS-Office of the Inspector General (OIG): CDC can refer possible violations of the select agent regulations to HHS-OIG. HHS-OIG can levy civil monetary penalties (up to $250,000 for an individual for each violation and up to $500,000 for an entity for each violation) or recommend criminal enforcement (imprisonment for up to five years, a fine, or both). 1 To view the law see: http://frwebgate.access.gpo.gov/cgi- bin/getdoc.cgi?dbname=104_cong_public_laws&docid=f:publ132.104. Accessed October 6, 2011. 2 To learn more about SRAs, see: http://www.selectagents.gov/sra.html. Accessed October 6, 2011. 3 See: http://www.selectagents.gov/resources/Session%201%20-%20RO%20Responsibilities.pdf. Accessed October 6, 2011. 4 For more information see: http://www.selectagents.gov/resources%5CSecurity%20Information%20Document.pdf. Accessed October 6, 2011. 5 See: http://www.hhs.gov/asl/testify/2007/10/t20071004c.html. Accessed October 6, 2011. 6 To view the checklists see: http://www.selectagents.gov/Checklists.html. Accessed October 6, 2011.

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196 Biosecurity Challenges Referral to FBI: CDC can refer possible violations involving criminal negligence or a suspicious activity or person to the FBI for further investigation.”7 Through June 29, 2011, the HHS Office of Inspector General (OIG) had accepted a total of $2,127,000 from 16 different organizations to settle allegations of failure to comply with select agent regulations.8 To provide oversight of the CDC and APHIS’s implementation, the HHS and USDA OIG also conduct audits of the Select Agent Program. In a 2006 HHS audit of 15 universities, OIG found that 8 had inventory weaknesses, 6 had weak security plans, and 6 had access control problems.9 In a 2006 USDA audit, OIG found multiple weaknesses with the methods that APHIS was using to oversee and regulate the Select Agent Program including an inadequate review of security plans, use of an out-of-date list of individuals with access, and inadequate facility inspections (OIG, USDA, 2006). In July 2010, Executive Order (EO) 13546, “Optimizing the Security of Biological Select Agents and Toxins in the United States,” created the Federal Experts Security Advisory Panel (FESAP), which was tasked to make recommendations to improve the Select Agents Program (Obama, 2010). To better match precautions to actual risks and reduce the impact of excessive security, EO 13546 instructed FESAP to (1) designate a subset of the select agent list as “Tier 1” agents and propose appropriate additional precautions and (2) consider whether any current select agents or toxins might be removed from the list. FESAP subsequently recommended 12 agents and toxins be designated as Tier 1 and 25 agents and toxins be removed from the list (FESAP, 2010). NIH The NIH’s Guidelines for Research Involving Recombinant DNA Molecules (RAC)10 provides oversight of laboratories whose investigators receive NIH funding and conduct experiments with recombinant DNA. While many experiments can be reviewed at the institutional level, some experiments require approval from the NIH. Many institutions that do not receive NIH funds voluntarily comply with the RAC guidelines as these are viewed as establishing best practices. The RAC guidelines require institutions to establish an Institutional Biosafety Committee (IBC) to review research proposals that would require the use of recombinant DNA. Reviews should include an assessment of the procedures, facilities, and practices that would be used in the experiment. The IBC can approve proposals or make recommendations for modifying experiments. In addition, the institution must have a biological safety officer who periodically inspects laboratories, reports violations to the IBC, and prepares emergency plans for dealing with accidental exposures or spills. OSHA The Occupational Safety and Health Administration (OSHA) has several mandatory laboratory standards. For example, OSHA Standard 29 CFR 1910.1450 (Occupational Exposure to Hazardous Chemicals in the Laboratory) requires, among other things, that laboratories have a Chemical Hygiene Plan, mandatory employee training, personal protective equipment (PPE) for certain chemicals, and accessible material safety data sheets for all hazardous chemicals.11 OSHA has also issued a Bloodborne Pathogen Standard, which provides guidance on preventing and responding to worker 7 See: http://www.hhs.gov/asl/testify/2007/10/t20071004c.html. Accessed October 6, 2011. 8 See: http://oig.hhs.gov/fraud/enforcement/cmp/agents_toxins.asp. Accessed October 6, 2011. 9 See: http://oig.hhs.gov/oas/reports/region4/40502006.pdf. Accessed October 6, 2011. 10 For the full NIH Guidelines for Research Involving Recombinant DNA Molecules, see: http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.htm. Accessed October 6, 2011. 11 Available at: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=10106. Accessed October 6, 2011.

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197 Appendix E: Country and Region Overviews exposure to blood.12 OSHA standards apply to public health laboratories and research laboratories at all biosafety levels. Other Regulators Many other government entities also play a role in regulation of biosafety and biosecurity in high- containment laboratories. The Departments of State, Commerce, and Treasury, for example, oversee export controls on biological products. Additionally, the Department of Transportation, the United States Postal Service, the International Civil Aviation Organization,13 and the International Air Transport Association14 all have regulations regarding the transportation of biological agents. 3. In the United States, are there established criteria for deciding: a. Whether or not to establish high-containment facilities? b. Where to place such facilities? The decision to establish facilities depends on whether the facility is funded by the federal government or will be privately funded. There are, in general, no established criteria for privately funded facilities at universities or private sector institutions on when and where to build facilities. Government facilities or facilities at universities or elsewhere that are funded by the government are established based on the needs and research agendas of individual agencies, and no single government agency has the overall responsibility for determining needed laboratory capacity (United States GAO, 2009a). For example, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 increased laboratory construction to support research efforts in several areas, including antimicrobial resistance and countermeasures research. Decisions on where to locate facilities are often made through a competitive bid process that solicits proposals from competing entities. The final location is picked based on the scientific and technical merit of a proposal as well as other factors, such as public support, transportation, and site accessibility. Risk assessments are conducted to assess the likelihood and consequences associated with possible pathogen releases (NRC, 2008). Construction of federally funded facilities also requires preparation of environmental impact statements and increasingly involves engaging the local community. c. What research will be done in such facilities? High-containment biological laboratories are used for basic research, applied research, medical product testing and evaluation, and animal efficacy15 studies (United States GAO, 2007). The research done at government-funded facilities includes both investigator-proposed projects and projects proposed by the sponsoring agencies. Grants are awarded competitively. DOD, NIH, and other government entities fund research grants. d. What scientific, technical, and management advice is available to governments when making their decisions? A number of groups and organizations provide advice on the subject including: National Research Council The National Research Council (NRC), which is a part of the National Academies, writes independent, expert reports to advise the government and increase public understanding on matters 12 Available at: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10051. Accessed October 6, 2011. 13 For more information, see: http://www.icao.int. Accessed October 6, 2011. 14 For more information, see: http://www.iata.org. Accessed October 6, 2011. 15 Information about “Animal Rule” studies to demonstrate efficacy for Food and Drug Administration (FDA) product licensure may be found in 21 CFR Parts 314 and 601: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=314 and http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=601. Accessed October 6, 2011.

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198 Biosecurity Challenges related to science, engineering, and medicine.16 The NRC has commented on risk assessments for several high-containment labs including facilities at Fort Detrick, Maryland (NRC, 2010a); Boston, Massachusetts (NRC, 2007); and Manhattan, Kansas (NRC, 2010b). The NRC has also issued a number of reports on biosafety and biosecurity. NSABB The National Science Advisory Board for Biosecurity (NSABB) was formed by 42 U.S.C. 217a, section 222 of the Public Health Service Act and is governed by the Federal Advisory Committee Act. The NSABB was created in response to the recommendations made in the 2004 NRC report, Biotechnology Research in an Age of Terrorism.17 It includes non-governmental voting members and non-voting members from 15 federal agencies and departments. Members’ areas of expertise cover a wide range of topics, including: microbiology, biodefense, food production, export controls, law, and others.18 The NSABB advises the Secretary of HHS and other government leaders on policies related to dual use research in the life sciences by issuing reports and recommendations. For example, in September 2011, NSABB released a report on Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility (NSABB, 2011). Working Group on Strengthening the Biosecurity of the United States Executive Order 14386,19 Strengthening Biosecurity of the United States, created the Working Group on Strengthening the Biosecurity of the United States on January 9, 2009. The Secretary of Defense and Secretary of HHS chair the group, which also consists of the Director of National Intelligence, the Director of the National Science Foundation, the Attorney General, and the Secretaries of State, Commerce, Agriculture, Transportation, and Energy. The group reviewed existing laws, regulations, and practices and made recommendations to the President in November 2009 in a report titled National Strategy for Countering Biological Threats.20 4. What standards exist for high biological containment laboratories in the United States for engineering and construction, licensing, safety, security, regular oversight, and certification? General Standards The CDC-NIH publication Biosafety in Microbiological and Biomedical Laboratories (BMBL), which is currently in its 5th edition, has served as the standard code of practice for biosafety since 1984 (United States HHS, 2009). The BMBL provides guidance on all areas of biosafety and biosecurity including decontamination, transportation, containment level recommendations, and agent-specific practices. BMBL guidelines have been widely adopted and are mandatory for research conducted using federal grants. Noncompliance may result in the loss of funding (CRS, 2009). Federal laboratories, and most other facilities built using federal funds, are built to standards established by the funding agency. For example, to receive NIH money, laboratory engineering and construction must comply with the NIH 16 See: http://www.nationalacademies.org/about/. Accessed October 6, 2011. 17 To view the report, go to: http://www.nap.edu/catalog.php?record_id=10827. Accessed October 6, 2011. 18 For more information on the NSABB see: http://oba.od.nih.gov/biosecurity/PDF/NSABB_Charter_508_accessible.pdf or http://oba.od.nih.gov/biosecurity/biosecurity.html. Accessed October 6, 2011. 19 To view the Executive Order see: http://edocket.access.gpo.gov/2009/E9-818.htm. Accessed October 6, 2011. 20 The report can be found at: http://www.whitehouse.gov/sites/default/files/National_Strategy_for_Countering_BioThreats.pdf. Accessed October 6, 2011.

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199 Appendix E: Country and Region Overviews Design Requirements Manual.21 Additionally, those laboratories that work with select agents or recombinant DNA must abide by those programs’ previously mentioned standards. Training Training is required for personnel whose labs fall under the jurisdiction of the OSHA standards, the NIH guidelines, or the Select Agent Program. Rather than being standardized, training is specialized to the agents, risks, and activities in which the trainee will engage. In the case of select agent work, refresher training must be provided annually (CRS, 2009). High-containment labs commonly supplement didactic training with mentored, within-laboratory training (Le Duc et al., 2008). Many organizations provide resources and guidelines for biosafety and biosecurity training: • The Sandia National Laboratories’ International Biological Threat Reduction Program aims to reduce biological threats worldwide by, among other things, promoting the responsible use of biological agents, equipment, and expertise and improving the understanding of accidental and deliberate biological risks.22 • The CDC has online course modules and exercises for training in biosafety and biosecurity.23 • University of Texas Medical Branch maintains the National Biocontainment Training Center that provides training in biosafety and biosecurity to United States and international students, as well as on-site fellowships offering mentored training for individuals preparing for work at BSL-4 and for containment laboratory managers and engineers.24 • Yale Center for Public Health has online course resources for biosafety training based on a course taught at the school, designed in part for those interested in implementing biosafety and biosecurity courses at their own facilities.25 • Biosafety and animal safety training tools are available on the American Biological Safety Association (ABSA) website.26 Commissioning Labs Although there is no formal regulatory requirement for “commissioning,” when a new lab is built, a commissioning process may take place to ensure the lab meets safety standards. Agencies often contract out the process of commissioning a laboratory. Some agencies, for example the NIH, have specific checklists27 and guidelines28 for commissioning. A similar process occurs in other agencies and generally follows the recommendations of the BMBL. The commissioning documents are part of what must be presented during the select agent inspection that will eventually authorize high-containment labs to begin work with select agents (CRS, 2009). 5. Have there been any high-containment lab accidents in the United States? a. If yes, how and why did accidents at high-containment facilities occur? b. How, to whom and when are they reported? c. Who has authority to investigate accidents? 21 See: http://orf.od.nih.gov/NR/rdonlyres/AF690C46-0388-4180-9603- 3060F3078F5F/25782/NIHDesignRequirementsManualver711.zip. Accessed October 6, 2011. 22 See: http://biosecurity.sandia.gov/. Accessed October 6, 2011. 23 See: http://www.cdc.gov/od/ohs/biosecurity_training/page2790.html. Accessed October 6, 2011. 24 See: http://www.utmb.edu/nbtc. Accessed October 6, 2011. 25 See: http://publichealth.yale.edu/ycphp/biosafety/biosafety.html. Accessed October 6, 2011. 26 See: http://www.absa.org/trainingtools.html. Accessed October 6, 2011. 27 Department of Health and Human Services, National Institutes of Health, Biosafety Level 3- Laboratory Certification Requirements. 28 The NIH is currently working on a new version of The NIH Model Commissioning Guide. Section 1-7 of the NIH Design Requirements Manual discusses commissioning: http://orf.od.nih.gov/NR/rdonlyres/AF690C46-0388-4180-9603- 3060F3078F5F/25782/NIHDesignRequirementsManualver711.zip. Accessed October 6, 2011.

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200 Biosecurity Challenges d. What disciplinary or legal actions can be taken? e. Have any steps been taken to minimize BSL laboratory accidents? Accidents, some of which result in laboratory-acquired infections (LAIs), occur regularly albeit at a low level in United States high-containment laboratories. For example, between 1982 and 2003, personnel at NIAID intramural laboratories worked with microorganisms for more than 3 million hours in BSL-3 laboratories or BSL-2 laboratories with BSL-3 practices and experienced a total of 29 exposures of which only 1 resulted in a clinical infection and 4 resulted in silent infections (Johnson, 2004). Laboratory accidents may result from either human error or equipment or engineering malfunction, and often the specific cause of a suspected LAI cannot be determined (Pike, 1979). FESAP recently proposed that occupational health programs be mandatory for individuals with access to Tier 1 agents, which would aid in identifying LAIs (FESAP, 2010). Table E9.4 contains a partial list of United States laboratory accidents. Additional information about LAIs observed in conjunction with United States containment lab work may be found in the NRC report, Protecting the Frontline in Biodefense Research: The Special Immunizations Program (NRC, 2011). Table E9-4 Examples of Accidents in United States Biosafety Labs. Location Agent Description Date Source Human Error New Hampshire Vaccinia Accidental exposure from needlestick 9/2007 CDC, 2008 unknown Potential exposure when employee stuck self 8/2007 Field, 2007 Yersinia pestis with broken scalpel blade Maryland Vaccinia Accidental exposure from needlestick 8/2007 CDC, 2008 University of South Worker drops plate and splashes self 7/2007 Field, 2007 Ricketssia Alabama prowazekii U.C. Davis Potential exposure due to needlestick 7/2007 Field, 2007 Brucella University of Iowa Tularemia Potential exposure due to needlestick 5/2007 Field, 2007 Iowa Vaccinia Accidental exposure from needlestick 5/2007 CDC, 2008 UT San Antonio Tularemia Workers entered lab wihout PPE, unlikely 4/2007 Field, 2007 exposure unknown Researcher ill because of improper 4/2007 Field, 2007 Brucella decontamination procedures Pennsylvania Vaccinia Accidental exposure from needlestick 10/2006 CDC, 2008 Saint Louis monkeypox Worker exposed from needlestick 8/2006 CDC, 2008 University University of Anthrax Worker exposed to Anthrax after needlestick 7/2006 CDC, 2008 Chicago Connecticut Vaccinia Accidental exposure from needlestick 3/2005 CDC, 2008 Children's Hospital Anthrax Scientists exposed after live anthrax samples 6/2004 CDC, 2008 and Research accidentally get shipped to the lab Center Oakland, CA USAMRIID Ebola Accidental exposure from needlestick 2/2004 Kaiser, 2007 unknown West Nile Virus Lab worker contacts virus after accidentally 12/2002 CDC, 2008 cutting finger with scalpel unknown West Nile Virus Lab worker contracts virus after needlestick 8/2002 CDC, 2008 University of Texas Cutaneous anthrax of lab worker 4/2002 Field, 2007 Anthrax USAMRIID Junin virus Bone fragment from monkey punctured finger 12/1982 Johnson, during autopsy 2004 USAMRIID Lassa virus Accidental needle stick in finger 11/1979 Johnson, 2004 Equipment/Engineering Error University of GA none Flooding occurred twice of high-containment 2008 Schneider laboratory after sterilizer failed to shut off and Hart, 2008 CDC CDC used duct tape to secure facility after air 2007 Young, Coxiella filtration system failed during maintenance 2008 burnetii

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201 Appendix E: Country and Region Overviews University of Anthrax Potential exposure from broken flask spill 8/2007 Field, 2007 Mississippi Medical Center University of Texas Anthrax Potential exposure after fluid discovered in 5/2007 Field, 2007 Health Science bottom of centrifuge Center unknown Potential exposure after cap came off tube 8/2006 Field, 2007 Brucella University of Virginia Tularemia Potential exposure from cracked tube 8/2006 Field, 2007 University of Worker exposed after autoclave bag leaked 5/2006 Field, 2007 Yersinia Pestis Kentucky Tufts University Botulinum Potential exposure after broken vial found in 4/2006 Field, 2007 neurotoxin centrifuge unknown Potential exposure after broken vial 9/2005 Field, 2007 Coccidioides containing agent found in centrifuge immitis Plum Island 3 hour power failure 12/2003 Santora, 2002 Rocky Mountain Open container fell off shaker 2001 Johnson, Yersinia pestis Laboratory 2004 Unknown/Miscellaneous Error unknown Blood tests show potential exposures of 10 2007 Field, 2007 Coxiella people to agents burnetii unknown Tularemia Potential exposure after bitten by infected 7/2007 Field, 2007 animal unknown Lab worker potentially scratched by infected 4/2007 Field, 2007 Yersinia pestis animal Lovelace Lab worker bit by infected animal 9/2006 Field, 2007 Yersinia pestis Respiratory Research Institute Texas A&M Lab workers infected while cleaning aerosol 2/2006 United Brucella chamber; failure to report to CDC States GAO, 2007 Public Health Infected mice missing 8/2005 Field, 2007 Yersinia pestis Research Institute at UMDNJ UNC-Chapel Hill Venezuelan Blood test show possible exposure 9/2004 Field, 2007 equine encephalitis Medical College of Lab worker contracts coccidioidomycosis, 8/2004 Field, 2007 Coccidioides Ohio unknown route of exposure immitis Boston University Tularemia 3 scientists infected with Tularemia over 5 2004 Field, 2007 Medical Center months Rocky Mountain Skin test converted; cause was likely 2000 Johnson, Mycobacterium Laboratory improperly inactivated samples 2004 tuberculosis Rocky Mountain Worker hospitalized and successfully treated 1998 Johnson, Chlamydia Laboratory with antibiotics; no specific cause determined 2004 trachomatis Yerkes Primate Simian Exposed research assistant dies 6/1998 Wrobel, Center Herpesvirus 1998 Rocky Mountain Skin test converted; no specific cause 1996 Johnson, Mycobacterium Laboratory determined 2004 tuberculosis Yale University Sabia Researcher contracts virus and exposes 75 8/1994 Glass, 1994 other co-workers Plum Island Foot and Accidental release of virus into holding pens 1978 Margasak, mouth disease 2008 SOURCE: NRC Staff.

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202 Biosecurity Challenges In the event of a theft, loss, or release of a select agent, the Select Agent Program currently requires a laboratory to notify the CDC and/or APHIS immediately (within 24 hours).29 Appropriate federal, state, or local law enforcement must also be notified in the event of loss or theft; health agencies, such as local employee health services, must be notified if there is a risk of human infection. Additionally, the facility must submit APHIS/CDC Form 3 within seven days of the incident.30 CDC or APHIS then conducts an investigation into the incident to determine the cause, actions that can be taken to mitigate future accidents, and whether further actions such as revocation of approval to work with select agents, fines, and/or potential criminal enforcement actions are needed. Laboratories not in the select agent program typically have their own rules for accident reporting. For example, overt or potential exposures in BSL-3 and BSL-4 labs that occur in the course of research subject to NIH Recombinant DNA guidelines must be reported to the NIH Office of Biotechnology Activities immediately. Increasingly, laboratories are making data on accidents publically available. For example, since 2002, University of Texas Medical Branch has published all incidents of laboratory accidents and potential exposures occurring in its research laboratories quarterly on its website.31 There have been several recent cases in which laboratories failed to report accidents in a timely manner. In 2006, Texas A&M did not report laboratory-acquired infections of Brucella and Coxiella burnetii that were later exposed through a Freedom-of-Information Act (FOIA) request.32 The CDC ultimately shut down select agent research at the laboratory until all problems identified in the subsequent investigation were addressed and the university agreed to pay a $1 million fine (Kaiser, 2008). At Boston University in 2004, three individuals who worked with a vaccine strain of Francisella tularensis (not a select agent) became ill with tularemia.33 While two of the cases occurred in May and one in September, none was reported to the public health authorities until November. An investigation revealed that their stock of the vaccine strain had became contaminated by unknown means with Type A F. tularensis, which is a select agent. OSHA proposed fines of $8,100 for each of Boston University and Boston Medical Center Corporation for their failure to ensure proper use of personal protective equipment.34 The lack of transparency at Boston University has greatly increased public concern about the new National Emerging Infectious Diseases Laboratory, for which the United States government is preparing additional risk assessments with advice from the National Research Council.35 6. Have any steps been taken to increase security at high biological containment facilities? While select agent rules do not mandate specific physical security requirements, BSL-4 laboratories are increasingly employing visible 24/7 armed guards, controlled access, vehicle barriers, and closed-circuit television monitoring (United States GAO, 2009b). Additionally, since 2008 many Department of Defense containment laboratories have been subject to Army Regulation 50-1, which established a biological ‘surety’ program that defines criteria for evaluating personnel reliability (Department of the Army, 2008). 29 See: http://www.selectagents.gov/resources/CDC- APHIS_Theft_loss_Release_Information_Document.pdf. Accessed October 6, 2011. 30 CDC/APHIS Form 3 is available at: http://www.selectagents.gov/TLRForm.html. Accessed October 6, 2011. 31 Safety and Security/Incident Reports. Available at: http://www.utmb.edu/gnl/safety/report.shtml. Accessed October 17, 2011. 32 To learn more about the Texas A&M incident see: http://www.cidrap.umn.edu/cidrap/content/bt/bioprep/news/sep1907biolab.html and http://www.sunshine-project.org/TAMU/CDCTAMUReport.pdf. Accessed October 6, 2011. 33 See: http://www.bphc.org/programs/cib/environmentalhealth/biologicalsafety/forms%20%20documents/tularem ia_report_2005.pdf. Accessed October 6, 2011. 34 See: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=NEWS_RELEASES&p_id=11351. Accessed October 6, 2011. 35 To view the NAS report, see: http://www.nap.edu/catalog.php?record_id=12208. Accessed 6 October 2011.

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203 Appendix E: Country and Region Overviews Additionally, FESAP made a number of security recommendations that will be considered during the next revision of the Select Agent Regulations (FESAP, 2010). In particular, FESAP: • Defined appropriate personnel reliability practices, including provisions for on-going monitoring, for individuals with access to Tier 1 agents and toxins and for individuals with access to other select agents and toxins; • Specified physical and cyber security requirements for facilities with Tier 1 agents and for facilities with other select agents and toxins; and • Recommended that facilities document protocols for shipping, storing, and receiving select agents and toxins. REFERENCES Centers for Disease Control and Prevention (CDC). 2008. Laboratory-Acquired Vaccinia Exposures and Infections—United States, 2005-2007. Morbidity and Mortality Weekly Report 57(15):401-404. Department of the Army. 2008. Nuclear and Chemical Weapons and Materiel: Biological Surety. Army Regulation 50-1. Headquarters, Department of the Army: Washington, D.C. 28 July 2008. 54 pp. [Online]. Available: http://www.fas.org/irp/doddir/army/ar50-1.pdf. Federal Experts Security Advisory Panel (FESAP). 2010. Recommendations Concerning the Select Agent Program. [Online.] Available: http://www.phe.gov/Preparedness/legal/boards/fesap/Documents/fesap-recommendations- 101102.pdf. Field, K. 2007. After Accidents, Laboratory Safety Is Questioned. The Chronicle of Higher Education 54(8):A19. Glass, S. 1994. Researcher at Yale gets virus after spill. Pittsburgh Post-Gazette August 22, 1994. [Online.] Available: http://news.google.com/newspapers?id=SIgNAAAAIBAJ&sjid=3m8DAAAAIBAJ&pg=6700,39275 04&dq=high+containment+lab+accident. Johnson, K.M. 2004. Appendix D: Review of Biocontainment Laboratory Safety Record. In: Final Environmental Impact Statement Integrated Research Facility Rocky Mountain Laboratories Hamilton, Montana / Biosafety BSL-4: More than 20 Years Experience at Three Major Facilities. National Institutes of Health, Bethesda, MD. pp D1-D18. Kaiser, J. 2007. Accidents Spur a Closer Look at Risks at Biodefense Labs. Science 317:1852-1854. Kaiser, J. 2008. Texas A&M to Pay $1 Million for Biosecurity Breaches. ScienceNOW February 20, 2008. [Online.] Available: http://news.sciencemag.org/sciencenow/2008/02/20-01.html. Kaiser, J. 2011. Taking stock of the biodefense boom. Science 333:1214-1215. Le Duc, J.W., K. Anderson, M.E. Bloom, J.E. Estep, H. Feldmann, J.B. Geisbert, T.W. Geisbert, L. Hensley, M. Holbrook, P.B. Jahrling, T.G. Ksiazek, G. Korch, J. Patterson, J.P. Skvorak, and H. Weingartl. 2008. Framework for Leadership and Training of Biosafety Level 4 Laboratory Workers. Emerging Infectious Diseases 14(11):1685-1688. Margasak, L. 2008. Accidents at Disease Lab Acknowledged. The Associated Press April, 11, 2008. [Online.] Available: http://www.foxnews.com/wires/2008Apr11/0,4670,AnimalDisease,00.html. National Research Council (NRC). 2007. Technical Input on the National Institutes of Health's Draft Supplementary Risk Assessments and Site Suitability Analyses for the National Emerging Infectious Diseases Laboratory, Boston University: A Letter Report. Washington, D.C.: National Academies Press. National Research Council. 2008. Technical Input on Any Additional Studies to Assess Risk Associated with Operation of the National Emerging Infectious Diseases Laboratory, Boston University: A Letter Report. Washington, D.C.: National Academies Press. National Research Council. 2009. Responsible Research with Biological Select Agents and Toxins. Washington, D.C: National Academies Press. National Research Council. 2010a. Evaluation of the Health and Safety Risks of the New USAMRIID High-containment Facilities at Fort Detrick, Maryland. Washington, D.C.: National Academies Press.

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204 Biosecurity Challenges National Research Council. 2010b. Evaluation of a Site-Specific Risk Assessment for the Department of Homeland Security's Planned National Bio- and Agro-Defense Facility in Manhattan, Kansas. Washington, D.C.: National Academies Press. National Research Council. 2011. Protecting the Frontline in Biodefense Research: The Special Immunizations Program. Washington, D.C.: National Academies Press. National Science Advisory Board for Biosecurity (NSABB). 2011. Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility. [Online.] Available: http://oba.od.nih.gov/biosecurity/pdf/CRWG_Report_final.pdf. Obama, B. 2010. Optimizing the Security of Biological Select Agents and Toxins in the United States. Executive Order 13546. July 2, 2010. [Online.] Available: http://www.gpoaccess.gov/presdocs/2010/DCPD-201000572.pdf. Office of Inspector General, United States Department of Agriculture (OIG, USDA). 2006. Audit Report: Animal and Plant Health Inspection Service Evaluation of the Implementation of the Select Agent or Toxin Regulations Phase II. Report No. 33601-3-AT. [Online.] Available: http://www.usda.gov/oig/webdocs/33601-3-AT.pdf. Pike, R.M. 1979. Laboratory-associated infections: incidence, fatalities, causes, and prevention. Annual Review of Microbiology 33:41-66. Public Law 107-56: Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism (USA Patriot Act) Act of 2001. (115 Stat. 272, 10/26/2001). [Online]. Available at: http://frwebgate.access.gpo.gov/cgi- bin/getdoc.cgi?dbname=107_cong_public_laws&docid=f:publ056.107.pdf. Public Law 107-188: Public Health Security and Bioterrorism Preparedness and Response Act of 2002. (116 Stat. 594, 06/12/2002). [Online]. Available: http://www.epa.gov/watersecurity/pubs/security_act.pdf. Santora, M. 2002. Power Fails for 3 Hours at Plum Island Infectious Disease Lab. The New York Times December 20, 2002. [Online.] Available: http://www.nytimes.com/2002/12/20/nyregion/power- fails-for-3-hours-at-plum-island-infectious-disease-lab.html?src=pm. Schneider, C. and A. Hart. 2008. Flooding at UGA germ lab revealed. The Atlanta Journal-Constitution November 2, 2008. [Online.] Available: http://www.ajc.com/metro/content/metro/stories/2008/11/02/lab_1102_2DOT.html. United States Congressional Research Service (CRS). 2009. Oversight of High-Containment Biological Laboratories: Issues for Congress. By: Gottron, F. and D.A. Shea. R40418, May 4, 2009. [Online.] Available: http://www.fas.org/sgp/crs/terror/R40418.pdf. United States Government Accountability Office (United States GAO). 2007. High-containment biosafety laboratories: Preliminary observations on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States. Testimony before the Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, House of Representatives. GAO-08-108T. Washington, D.C. [Online. Available: http://www.gao.gov/new.items/d08108t.pdf. United States Government Accountability Office. 2009a. High-containment laboratories: National strategy for oversight is needed. Report to Congressional Requesters. GAO-09-574. Washington, D.C. [Online]. Available: http://www.gao.gov/new.items/d09574.pdf. United States Government Accountability Office. 2009b. Biosafety Laboratories: BSL-4 Laboratories Improved Perimeter Security Despite Limited Action by CDC. GAO-09-1038T. Washington, D.C. [Online.]. Available: http://www.gao.gov/new.items/d091038t.pdf. United States Department of Health and Human Services (United States HHS). 2009. Biosafety in Microbiological and Biomedical Laboratories. 5th Edition. HHS Publication No. (CDC) 21-1112. Washington, D.C. 438 pp. [Online]. Available: http://www.cdc.gov/biosafety/publications/bmbl5/BMBL.pdf. Wrobel, S. 1998. Yerkes 'family' pulled together after death of young researcher from rare Herpes B infection. Emory Report 50(16). Young, A. 2008. CDC action at germ lab questioned. The Atlanta Journal-Constitution June 22, 2008. [Online.] Available: http://www.ajc.com/search/content/news/stories/2008/06/22/cdclab.html.