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Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options (2012)

Chapter: 4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats

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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Page 70
Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Page 73
Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Page 74
Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Page 100
Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Page 101
Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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Suggested Citation:"4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats." National Research Council. 2012. Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Options. Washington, DC: The National Academies Press. doi: 10.17226/13454.
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4 Analysis and Conclusions about Three Approaches for Providing US Infrastructure to Counter Foreign Animal Disease and Zoonotic Disease Threats As part of its statement of task, the committee was asked to analyze three options for achieving the infrastructure needed to address threats posed by for- eign animal diseases (FADs) and zoonotic diseases. Those options are building the National Bio- and Agro-Defense Facility (NBAF) as currently designed, building a version of the NBAF of reduced size and scope to be described by the committee, and maintaining the Plum Island Animal Disease Center (PIADC) in conjunction with obtaining biosafety level 4 (BSL-4) livestock capacity through partnerships with foreign laboratories. The committee analyzed the options with regard to how they might achieve an overall integrated US system that incorpo- rates the critical core functions of disease surveillance, diagnostics, outbreak response and recovery, research and development, and workforce training de- scribed earlier in this report, as well as expected future needs (see Chapter 3). Successful implementation of those critical systemwide functions requires prac- tical infrastructure and laboratory capacity. This chapter provides a brief history of previous long-term planning efforts, which demonstrates that many of the same issues have plagued the US system for addressing FAD and zoonotic dis- ease threats for many years. The history provides context for the committee’s current analysis. This is followed by the committee’s assessment of what the needed research and diagnostic laboratory infrastructure would include, regard- less of the option considered for the central laboratory facility. In subsequent sections, the committee discusses the three options and assesses how they ad- dress capacity needs, such factors as relative costs, and other considerations. 67

68 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE PREVIOUS LONG-TERM PLANNING EFFORTS In 1983, the National Research Council released the report Long-Term Planning for Research and Diagnosis to Protect U.S. Agriculture from Foreign Animal Diseases and Ectoparasites (NRC, 1983). The study was requested in 1982 by the US Department of Agriculture (USDA) to “assess the current state of the USDA effort on FAD&E [foreign animal diseases and ectoparasites] di- agnosis and research; assess, for three 10-year increments, current and projected technology of biological containment; and assist USDA in planning, in three 10- year increments, for research on and diagnosis of all FAD&E of livestock and poultry” (NRC, 1983). The deliberations and recommendations in the 1983 report have a strong resonance with the questions posed to the current National Research Council committee 30 years later. Main themes of the 1983 report were that the facilities at PIADC for conducting FAD and ectoparasite research and diagnostics were obsolete and that the United States needed to contemplate several options to maintain strong protection of our animal industries and economy in the face of a threat of FADs and ectoparasites. In addition to recommendations that addressed the need for long-term research planning and coordination, the 1983 NRC report said that  “USDA should increase coordination [of FAD&E activities] with other federal agencies and foreign institutions” (NRC, 1983).  “USDA should establish a system of laboratories and university-based collaborative research centers for investigation, research, and diagnosis of do- mestic and foreign animal diseases and ectoparasites” (NRC, 1983).  “As soon as possible, USDA should proceed with construction of a new, highly secure mainland laboratory to succeed PIADC as USDA’s principal cen- ter for research on exotic airborne and fomites-transmitted non-avian animal diseases” (NRC, 1983). The report further suggested the need for BSL-4 capabilities and proximity to a major airport and a major university campus to ensure ready access and a supportive scientific environment. It also suggested that PIADC be maintained for large-animal challenge and vaccine studies in view of the legal restrictions on working with foot-and-mouth disease virus (FMDv) on the mainland. Eleven years later, in 1994, USDA appointed a Task Force on Biocontain- ment Facilities for Foreign Animal Disease Research and Diagnostic Activities (USDA, 1994) to consider two issues: the progress made in the preceding dec- ade in new technology development and use for handling FAD agents since the publication of the 1983 National Research Council report, and the current status of and physical requirements for large-animal biocontainment facilities for con- ducting FAD research and diagnostic activities in the near term and the long- range future.

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 69 Regarding progress on research and diagnostic technologies, the 1994 task force indicated that in vitro modern technologies were available for studying FAD pathogens but that the use of in vivo studies was still needed for  The isolation of etiological agents to activate federal programs for dis- ease control and eradication, particularly in the case of new emerging pathogens that could not be isolated in vitro.  Conducting pathogenesis studies and proving Koch’s postulates.  Continuing to train state and federal veterinarians in the recognition of FADs by using live-animal reproduction of key FADs. Those justifications of a facility with the capability for live-animal studies under strict biocontainment remain highly relevant today and were previously discussed in Chapters 2 and 3 of this report. Regarding the status of facilities to conduct FAD research and diagnostic activities, the 1994 task force found that despite the recommendations of the 1983 National Research Council report, the PIADC facilities remained badly in need of upgrading to achieve world-class designation. In 1994, an estimated $80-100 million was needed for repairs and upgrades. There have been periodic upgrades and renovations of PIADC since the 1994 report, but the general state of PIADC in 2012 has not changed. The task force also pointed out that several existing or planned facilities on university campuses may be capable of FAD research and diagnostic activities but that many of them may have obsolete technologies, may be underused, or have not been adequately maintained. As previously discussed in Chapter 3, however, the status of university and federal facilities in 2012 is substantially different from that in 1994. Finally, the 1994 task force offered nine potential options regarding the future of PIADC, catego- rized into three groups as listed below. The reader is referred to that report for additional information on options that are not presented in detail below. Group One—Retain Plum Island Operations Options 1-4: Several possibilities for achieving this recommendation were presented, but they are not central to this report. Group Two—Relocate Plum Island Operations to a Mainland Site Option 5: Construct new mainland FAD facilities. “Request an upfront, lump-sum appropriation, and construct new FAD facilities at a mainland site. Continue to use existing FAD facilities on Plum Island until construction is completed on the mainland. Continue to conduct domestic disease and selected FAD work in separate mainland facilities” (USDA, 1994). Option 6: Construct new mainland facilities; consolidate domestic and FAD work. “Request an upfront, lump-sum appropriation, and construct new FAD facilities at a mainland site (for both domestic and FAD work). Continue to use

70 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE the existing island and mainland facilities until construction is completed on the mainland. Consolidate both foreign and domestic animal disease work at the new mainland facilities” (USDA, 1994). (The completion of the National Cen- ters for Animal Health in Ames, Iowa, now supersedes the consideration of con- solidation of domestic and FAD facilities in a single facility.) Option 7: Upgrade Plum Island for foot-and-mouth disease work only; move other work to the mainland. “Request partial appropriations each year as required to upgrade/repair the Plum Island facilities, but [in view of the legal restrictions on working with foot-and-mouth disease virus on the mainland] only to the extent needed to conduct live-animal FMD challenge work. Relocate all other FAD activities to existing mainland sites” (USDA, 1994), such as the Na- tional Animal Disease Center, the National Veterinary Services Laboratories, the Southeast Poultry Research Laboratory, and the Arthropod-Borne Animal Diseases Research Laboratory. Group Three—Unacceptable Options Option 8: Upgrade Plum Island for foot-and-mouth disease work; contract other FAD work. “[Maintain] a small Plum Island unit for FMD studies and [contract] all other FAD activities with universities on the mainland. This option was discarded because it would have afforded insufficient control and oversight to ARS and APHIS [the USDA Agricultural Research Service (ARS) and Ani- mal and Plant Health Inspection Service (APHIS)], required large expenses for renovated or new university containment facilities, and continued expenditures at Plum Island” (USDA, 1994). (But with the construction of multiple new bio- containment facilities throughout the United States since the 1994 report was issued, the present committee views that this option should no longer be consid- ered unacceptable, as discussed further below.) Option 9: Have ARS and APHIS seek independent decision-making and funding. “Option 9 would have isolated ARS and APHIS, setting each agency off on its own to seek independent answers, decision making, and funding. This option was discarded because it would have meant less control and oversight of FAD work by ARS and APHIS, and it would have led to higher overall costs” (USDA, 1994). Additional USDA, Department of Homeland Security (DHS), and National Research Council reports echoed many of those issues, including concerns that the PIADC facilities were at the end of their lifespan and needed modernization and other upgrades and that a facility with BSL-4 large-animal capabilities was needed (USDA, 1999; NRC, 2005; DHS, 2007a,b, 2008a; CRS, 2008; 74 Fed- eral Register, 2009).

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 71 Previous National Research Council reports provide a historical perspective for consideration of the three options specified in the present committee’s state- ment of task. However, the committee’s deliberations were conducted independ- ently of previous report recommendations to ensure that the current context of disease threats, the ideal infrastructure to counter the threats, the technology of “today and tomorrow”, and the current US and global assets available for coun- tering disease threats informed the current study. Nevertheless, previous rec- ommendations remain, in part, as relevant today as they were in 1983, 1994, and later. The following sections discuss the three options the committee was asked to address with respect to capacity and capabilities, advantages and liabilities, relative costs, and other considerations. THE LABORATORY INFRASTRUCTURE NEEDED FOR A FOREIGN ANIMAL DISEASE AND ZOONOTIC DISEASE RESEARCH AND DIAGNOSTIC FACILITY, REGARDLESS OF LOCATION AND SIZE A US system to address the potential threats posed by FADs and zoonotic diseases effectively must include the ability to conduct research and diagnostic procedures, provide training to support a competent and prepared workforce, and include specialized facilities for handling particular pathogens and for con- ducting experiments in large animals. The facility and program components of the ideal system are depicted in Figure 3-1, and a more detailed description of the laboratory infrastructure that would be required to meet those objectives is described below. The numbers beside the headings below correspond to the numbers in Figure 4-1. System Components 1 2 3 4 5 6 Option 1 NBAF Option 3 PIADC 2 1 Option 2 NAHLN, RBL/NBL, 1 Streamlined 2 Private Sector 3 3 6 NBAF 3 1 5 3 4 2 6 3 Academe 5 4 Academe 1 5 1 5 4 Academe, 6 NAHLN, RBL/NBL, 6 NAHLN Private Sector 5 4 Private Sector, RBL/NBL, Academe Academe, NAHLN National BSL-4 Labs, 4 International BSL-4 Labs National BSL-4 Labs, 6 International BSL-4 Labs Private Sector, RBL/NBL, Academe FIGURE 4-1 Comparison of the three options analyzed by the committee with the com- ponents of an ideal laboratory infrastructure. The examples given are for illustration only

72 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE and are not meant to be inclusive. See Table 4-1 for more detail. NOTE: 1 = diagnostics, 2 = research on foot-and-mouth disease, 3 = research on non- foot-and-mouth disease FADs and zoonotic diseases in BSL-3Ag facilities, 4 = special pathogen activities in ABSL-4 and BSL-4 facilities, 5 = teaching and training, 6 = vaccine development. NAHLN = National Animal Health Laboratory Network; RBL/NBL = Regional Biocon- tainment Laboratories and National Biocontainment Laboratories. Diagnostics (1) Laboratory infrastructure for the isolation, identification, and diagnosis of FADs and zoonotic diseases is needed at several levels of biocontainment. In vitro diagnostic work with inactivated pathogens or pathogen components may be conducted with BSL-2 containment. Such work would include identification of an agent with nucleic acid-based methods, such as the polymerase chain reac- tion (PCR); detection of antigens with antibody-based methods, such as the en- zyme-linked immunosorbent assay (ELISA); or characterization of host immune responses to key agent antigens. In addition, reference reagent preparation (when working with inactivated pathogen material), proficiency-testing panels, and other activities related to support for state-based testing laboratories can be conducted with BSL-2 containment. In vitro diagnostic work and the isolation of live pathogens may generally be conducted in space at BSL-2, BSL-3, or BSL-4 levels. BSL-3Ag space is generally not required for working in vitro.1 Research on Foot-and-Mouth Disease (2) Ease of transmission and the potential for large economic effects of an out- break of foot-and-mouth disease make it a disease of special consideration. Ac- tive research is ongoing to develop diagnostics for and vaccines against foot- and-mouth disease virus (FMDv) strains. Currently, foot-and-mouth disease research can be conducted in only one US facility: PIADC, off the US mainland. Because of the special circumstances and restrictions surrounding foot-and- mouth disease research, the committee considers it separately. In vitro work on foot-and-mouth disease is conducted at BSL-3E level, and in vivo experiments with FMDv are conducted at the BSL-3Ag level. 1 The 5th edition of Biosafety in Microbiological and Biomedical Laboratories sup- ports conducting in vitro work with animal pathogens at the BSL-3 level, restricting the use of BSL-3Ag to only situations in which particular FAD agents are used in infectivity studies and when animals are loose in an isolation room (in which the walls of the room itself form the primary containment barrier). Those agents are African swine fever virus, lumpy skin disease virus, highly pathogenic avian influenza virus, Mycoplasma mycoides subsp. mycoides (small colony type), Mycoplasma capricolum, Newcastle disease virus (velogenic strains), Peste des petits ruminants virus (plague of small ruminants), Rift Valley fever virus, rinderpest virus, classical swine fever virus, and foot-and-mouth dis- ease virus (CDC, 2009).

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 73 Research on Foreign Animal Diseases and Zoonotic Diseases in BSL-3Ag Facilities (3) The necessary laboratory infrastructure for in vivo experiments on many FADs and zoonotic diseases includes animal holding facilities for microbiologi- cal, immunological, and pathogenesis studies at BSL-3Ag and ABSL-3E level containment. Experiments at ABSL-3E can occur where animals are housed in cages. BSL-3Ag containment is required for in vivo experiments on large ani- mals that must be housed directly in an isolation room. In addition, the capabil- ity to conduct in vivo studies of some pathogens associated with arthropod vec- tors requires BSL-3Ag facilities. A separate set of guidelines, known as Arthropod Containment Levels, is used to define the biocontainment needed for safe manipulation of live arthropods (ASTMH, 2003). Special Pathogen Activities in ABSL-4 and BSL-4 Facilities (4) Research with some pathogens can be conducted only at BSL-4 or ABSL-4 containment. Those pathogens currently include hemorrhagic fever viruses (such as Crimean-Congo hemorrhagic fever virus) and the new genus of Henipavirus in the Paramyxoviridae family (Nipah and Hendra viruses).2 BSL-4 laboratory capabilities are also needed more generally as part of an effective US system to counter FAD and zoonotic disease threats because of the possible emergence of new highly contagious zoonotic pathogens. In particular, BSL-4 and ABSL-4 will be required for initial work on newly emerging or unknown diseases in or- der to provide protection to researchers from unknown biological hazards until these can be more fully characterized. The required laboratory capacity includes the ability to undertake in vitro microbiological research, such as propagation 2 The primary reservoir for Henipaviruses is bats of the Pteropus family, whose range includes the eastern coastal areas of Australia, Southeast Asia, and South Asia. Hendra virus was first recognized in 1994, and outbreaks have occurred only in Australia; Nipah virus was first recognized in 1998, and outbreaks have occurred in Malaysia, Bangladesh, and India. The probability of a natural introduction and establishment of either Nipah virus or Hendra virus in the United States is small, and an outbreak in animals or people is unlikely to lead to establishment of either one of these two viruses in the Western Hemisphere, because of the absence of the primary vector or reservoir bat species. How- ever, capabilities to work with viruses that require BSL-4 and ABSL-4 conditions, such as Hendra virus and Nipah virus, are desirable for counter-bioterrorism and for potential vaccine development, primarily for human or animal use in endemic areas. Active re- search on Nipah and Hendra viruses is under way at BSL-4 facilities in the United States (in vitro and in vivo) and in Australia and Canada (in vitro and in livestock animal mod- els), and active research on vaccines with cloned proteins is going on at several BSL- 2/BSL-3 laboratories in the United States and abroad.

74 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE and basic characterization of pathogens, at the BSL-4 level.3 Facilities for in vivo experimentation in animal systems are also required at the BSL-4 level, as is a necropsy room for postmortem examinations on both small and large ani- mals. ABSL-4 facilities are required for in vivo experiments. Teaching and Training (5) The facilities necessary to train a prepared workforce include teaching classrooms outside primary containment and laboratory facilities at several con- tainment levels. Animal holding facilities for the in vivo demonstration of clini- cal and pathological manifestations of selected diseases in small animals housed with primary containment cages require ABSL-3E or ABSL-3.4 Animal holding facilities for in vivo demonstration in larger animals requires BSL-3Ag. A ne- cropsy room for training and demonstration purposes is required at the BSL-3Ag level. Vaccine Development (6) Laboratory experiments as part of vaccine or other product development for FADs and zoonotic diseases (except for special pathogens) will require BSL-3 and BSL-3E facilities. In vivo pathogen challenge and vaccine efficacy experi- ments in large animals will require BSL-3Ag. Examination of the Three Options With those requirements providing a framework, the committee turned to a fuller discussion of the three options presented in the statement of task. The op- tions are depicted in Figure 4-1, with demonstration of one example of several possible configurations for Options 2 and 3, and presented in greater detail with multiple examples in Table 4-1. 3 As noted earlier, BSL-4 containment is not required for basic diagnostic work with inactivated pathogens and non-replicating methodologies, such as PCR and other nucleic acid detection procedures. 4 For example, work with avian influenza in chickens housed in ventilated cages at the ABSL-3 level.

TABLE 4-1 Possible Location of Key Laboratory-Based Components of the Ideal System for Countering Foreign Animal Disease and Zoonotic Disease Threats RBL/NBL Private National International NBAF as NBAF- BSL-3 BSL-3Ag Sector BSL-4 BSL-4 Components Designed Streamlined NAHLN Laboratories Academe Laboratories Laboratories Laboratories Diagnostics In vitro— X X X nonviable/performance In vitro— X O X X X nonviable/development In vitro—viable X X agents/performance In vitro—viable X O X X agents/development In vivo diagnostics X X O O (animal inoculations) National reference function X X Foot-and-mouth disease virus research In vitro activities X X In vivo activities X X (including training) FAD research (non- foot-and-mouth disease) In vitro BSL-3/BSL-3E X X O O In vivo BSL-3Ag X X O (Continued) 75

76 TABLE 4-1 Continued RBL/NBL Private National International NBAF as NBAF- BSL-3 BSL-3Ag Sector BSL-4 BSL-4 Components Designed Streamlined NAHLN Laboratories Academe Laboratories Laboratories Laboratories Zoonotic disease research BSL-3/BSL-3E X O X X BSL-4 X X X X Training using animals FADs except X O O X foot-and-mouth disease Vaccine development Development of principle X O O O O Proof of principle X O O O O Scale-up development X X Animal efficacy studies X X O NOTE: X = principal location, O = optional location.

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 77 Figure 4-1 and Table 4-1 focus on potential US partnerships to address key laboratory components of an ideal system to address FAD and zoonotic disease threats, with the exception of international BSL-4 laboratory capacity, since this was included in the committee’s task as part of option 3. However, the commit- tee also notes that international collaborations can be developed to contribute to laboratory infrastructure at other biosafety levels, such as BSL-3Ag. ANALYSIS OF OPTION 1: THE PROPOSED NATIONAL BIO- AND AGRO-DEFENSE FACILITY AS CURRENTLY DESIGNED The Capacity and Capabilities of the Proposed National Bio- and Agro-Defense Facility The NBAF is envisioned as a modern laboratory resource for consolidating the research, diagnostic, and training missions of DHS and USDA (specifically, APHIS and ARS) in a single facility. Activities that would be conducted in the proposed NBAF include studies of high-consequence FADs and zoonotic dis- eases that pose a threat to the US animal industry—such as foot-and-mouth dis- ease, African swine fever (ASF), and classical swine fever (CSF)—and studies of emerging zoonotic and high-threat exotic agents that affect livestock and re- quire high containment at the ABSL-4 level. According to DHS’s Updated Site- Specific Biosafety and Biosecurity Mitigation Risk Assessment (DHS, 2012a), the NBAF, once operational, would support or provide  Basic and applied research on transboundary (foreign), emerging, and zoonotic diseases.  Enhanced ability to perform laboratory diagnostic detection of and re- spond to FADs and zoonotic diseases.  Expanded and dedicated space for development of vaccines and other countermeasures.  Training facilities for animal health specialists to improve US capabil- ity of detecting and responding to FADs of high consequence. The proposed NBAF campus, with an area of 715,000 gross ft2, would pro- vide infrastructure needed by DHS and USDA to meet their program require- ments and would provide supporting facilities (DHS, 2012b). In addition to cur- rent mission needs, DHS, APHIS, and ARS propose to expand their relevant research and development activities and have designed NBAF with that in mind. ARS proposes to expand its programs on emerging and zoonotic pathogens be- yond FMDv, CSF virus, and ASF virus and to expand its research program on vector-borne diseases. APHIS anticipates expanding its activities related to di- agnostic services and reference materials for emerging and zoonotic diseases and to enhance FAD diagnostics and training. DHS anticipates expanding its research programs on the development of new foot-and-mouth disease vaccines

78 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE and adding research on countermeasures for other high-priority FADs and zoonotic diseases (Colby, 2012; Kappes, 2012; Lautner, 2012). (Budgets for operational expenses of the NBAF were not part of the charge of this study. The committee notes that the anticipated expanded activities must be accompanied by a corresponding operational budget increase to each agency, however no data on research or diagnostic budgets for expanded programs were received.) Much of the space in the NBAF main laboratory would be occupied by the biocontainment zone, which includes BSL-3E, BSL-3E Special Procedures, BSL-3Ag, BSL-4, ABSL-4 laboratories, and supporting facilities. The BSL-4 space would be suitable for large-animal research and would include space for ABSL-4 large-animal holding and ABSL-4 large-animal necropsy facilities. Table 4-2 summarizes the features of the proposed NBAF and the purpose of each feature. Table 4-3 summarizes the animal-holding capabilities. According to DHS, the total projected annual animal counts for the facility, based on 70% space use, is “approximately 1,233 animals with a distribution of 519 bovine, 491 swine, 180 mice, 25 rabbits, 8 equine, 6 guinea pigs, [and] 4 goats” (DHS, 2012b). Analysis of Option 1: Laboratory Capacity The NBAF as currently designed is meant to serve as a single facility to span the array of required biosafety containment levels and to include pilot-scale vaccine-development production capabilities, which would enable it to include all of the types of laboratory capability and capacity required for an ideal system as described above. According to DHS, ARS, and APHIS, the agencies undertook a design re- view process to “right-size” the facility to ensure that space would align with agency mission needs and minimize substantial excess capacity. As part of this process, the net BSL-4 space was reduced by 2,025 ft2 and the net BSL-3Ag and BSL-3E space by 31,466 ft2 from the initial design phase in 2009 to the 65% design phase in 2011. The projected animal-room use chart provided by the agencies anticipates about 70% average occupancy, with the estimated occu- pancy of different types of rooms being about 50-90% (DHS, 2012b). The NBAF has been designed with the ideal system in mind so that it could be self-sufficient. The committee agrees that the proposed facility (based on the 65% design phase plans) would provide the needed capability and capacity to meet US needs. The committee also notes that the Western Hemisphere lacks sufficient ABSL-4 large-animal capacity; the only laboratory in North and South America is in Winnipeg, Canada and this facility has very little large-animal space. That is striking when one considers that countries such as the UK, Ger- many, and Switzerland, perhaps recognizing that zoonotic disease knows no boundaries, have each invested in BSL-4 space within their borders. There are also potential opportunities for some types of capacity to be provided through partnerships with other state, federal, and university laboratories in the United

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 79 States. That option is discussed in more detail under Option 2. Although the NBAF is designed to provide the range of required laboratory capabilities in a single facility, if it were to be operated in a stand-alone fashion without drawing on the nation’s physical and intellectual capital, it would not meet the needs of an ideal US system to address FADs and zoonotic disease threats. However, the committee notes that building the NBAF as designed does not preclude the NBAF from functioning as part of such an integrated and collaborative system. TABLE 4-2 Summary of NBAF Capacity and Capabilities Feature and Total Area Purpose BSL-2 space (19,402 gross ft2; Allowing improved throughput and multiagency use; 9,701 net ft2) examination and processing of FBI samples (to be passed into BSL-3E or held at BSL-2 for testing at Ames if found to be foot-and-mouth disease-free); housing of arthropods procured from vendors and other laboratories or rearing of arthropods; insect- vector research; space for packaging and shipping reagents to collaborators BSL-3Ag laboratories (animal Allowing additional parallel vaccine trials for FADs holding rooms, necropsy rooms, and zoonotic diseases; shared common core support services functions, laboratories to provide optimal flexibility and including laundry, loading dock, efficiency of space; animal holding rooms to house decontamination service, office various species of different sizes in BSL-3Ag operations) (215,700 gross ft2; environment; two necropsy rooms—one dedicated 53,925 net ft2) to research and diagnostic programs, the other to FAD training program BSL-3E laboratories, including Allowing associated laboratory research and BSL-3E Special Procedures diagnostic work; special-procedures laboratory— laboratory (149,840 gross ft2; core facilities for centrifugation and other aerosol- 37,460 net ft2) generating activities to support BSL-3Ag and BSL-4 research and includes additional level of high- efficiency particulate air filtration BSL-4 animal and laboratory Allowing USDA-ARS to conduct FAD and zoonotic space (53,624 gross ft2; disease research; allowing USDA-APHIS to perform 13,406 net ft2) diagnostic test development and validation, reagent production, and diagnostic specimen testing; allowing DHS (in partnership with USDA-ARS and USDA- APHIS) to develop countermeasures for veterinary and other high-consequence zoonotic diseases BSL-2 biotechnology development Allowing manufacture of materials for conducting module (pilot production facility) and supporting efficacy studies to provide preliminary (41,955 gross ft2; 8,300 net ft2) toxicology or general safety data for manufacture of larger volume of early clinical-phase materials SOURCE: DHS, 2012b; Johnson and Barrett, 2012.

80 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE TABLE 4-3 Numbers and Types of Large Animals that can be Handled in the Proposed NBAF Animal Rooms Room Typea No. Rooms Anticipated Animal Capacity per Room BSL-3Ag 4 Cattle 2 @ <1,430 lb or 4 @ <770 lb or 6 @ <440 lb; A OR swine 16 @ <220 lb; OR sheep 18 @ <110 lb BSL-3Ag 15 Cattle 2 @ <770 lb or 3 @ <440 lb; OR swine 6 @ <220 lb; A2 (10 x 12 ft) OR sheep 8 @ <110 lb BSL-3Ag 20 Cattle 1 @ <1,430 lb or 2 @ <770 lb or 3 @ <440 lb; A2 (12 x 12 ft) OR swine 8 @ <220 lb; OR sheep 9 @ <110 lb BSL-3Ag 1 Cattle 2 @ <1,430 lb or 4 @ <770 lb or 6 @ <440 lb; A3 OR swine 16 @ <220 lb; OR sheep 18 @ <110 lb BSL-3Ag 3 Cattle 4 @ <1,430 lb or 8 @ <730 lb or 12 @ <440 lb; B OR swine 32 @ <220 lb; OR sheep 36 @ <110 lb BSL-3Ag 2 Cattle 9 @ <1,430 lb or 16 @ <770 lb or 24 @ <440 lb; C OR swine 48 @ <220 lb; OR sheep 57 @ <110 lb BSL-3Ag 1 Cattle 12 @ <1,430 lb or 21 @ <770 lb or 32 @ <440 lb D BSL-4 2 Equine animals 2 @ <1,440 lb; OR cattle 2 @ <1,440 lb or (can also be used 4 @ <770 lb or 6 @ <440 lb; OR swine 8+ @ <110 lb or as BSL-3Ag 16+ @ <55 lb; OR sheep 8+ @ <110 lb or 16+ @ <55 lb swing space) Additional small- — Mice, rabbits, guinea pigs, and so on animal rooms SOURCE: DHS, 2012b. a Room designations A, A2, A3, C, and D represent different BSL-3Ag animal room de- signs; these designations are included in the 65% NBAF design phase plans (see Figure 4-2). Analysis of Option 1: Relative Costs and Other Considerations The 2012 estimate for NBAF’s construction cost is $1.14 billion, of which $824 million remains to be funded. In FY 2020, the expected first full year of operations, the facility is estimated to require operation and maintenance (O&M) costs of $46-$52 million in operations, management, and security and $6 million in the salaries of federal DHS staff. The NBAF is expected to include about 350 full-time equivalent staff (DHS, ARS, APHIS, and contractors), in- cluding researchers. For O&M and security, DHS estimates a need for 194 con- tractor staff (142 for O&M and 52 for security) and 36 DHS staff. Hence, the estimated number of full-time equivalent DHS and USDA research staff appears to be about 120. Estimated construction costs per gross ft2 of the main laboratory building range from $203 for general building support space to $1,197 for BSL- 4 space, with an average cost of $797 per gross ft2 for the whole facility. Based on the 65% design estimates, the estimated operational cost is $90 per gross ft2 in 2020 (Johnson and Barrett, 2012).

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 81 As a very rough comparison, the recently constructed DHS National Biode- fense Analysis and Countermeasures Center was estimated to cost $143 million to construct (Mary Goobic, DHS, personal communication, May 7, 2012), a facility with approximately 160,000 gross ft2 (10,500 net ft2 BSL-4, 34,000 net ft2 BSL-3, and 11,000 net ft2 BSL-2 laboratory space) (www.bnbi.org/faq.html). The Biosecurity Research Institute (BRI) at Kansas State University is a new facility with approximately 113,000 gross ft2 facility and has BSL-3 and BSL- 3Ag capabilities. The BRI had an estimated construction cost of $54M (www.bri.k-state.edu). The Friedrich-Loeffler-Institut in Germany also recently completed construction on their high-biocontainment facility which contains BSL-3Ag and ABSL-4 large-animal capacity and approximately 841,000 gross ft2 and 237,000 net ft2 (Mettenleiter, 2012). The estimated cost for constructing the new facility is €300 million, or about US $375 million at recent exchange rates for 2012 (Mettenleiter, 2012). However, such figures are difficult to com- pare directly, and the committee notes that a portion of the increased construc- tion costs for the NBAF derives from facility hardening and the results of site- specific risk assessments. According to DHS, “the NBAF cost per ft2 data in- cludes additional costs to meet the recommendations provided in the site- specific risk assessment. These site-specific cost factors should be noted when comparing NBAF cost data to similar facilities” (DHS, 2012b). In contrast, costs for some aspects of the facilities and security at the proposed NBAF could be lower than those currently associated with PIADC; for example, there would be no need for boat transportation to the remote location and no need for secure landing docks in New York, Connecticut, and Plum Island. It was explicitly be- yond the committee’s charge to consider site locations of the proposed NBAF; the committee notes these issues only to the extent that they are related to its task to examine the relative costs of the three options that it was asked to dis- cuss. Although the committee was not given detailed construction cost break- downs for the proposed NBAF, the overall costs of construction appear to be much greater than costs of comparable recent construction of other biocontain- ment facilities, including those requiring BSL-4 containment space. For exam- ple, the Galveston National Laboratory (GNL, completed in 2008) at the Uni- versity of Texas Medical Branch in Galveston was specifically hardened to withstand hurricane-force conditions. The two facilities clearly differ in size and missions, but the difference in construction costs (about $175 million for the GNL) seems high. The substantial proposed costs of the NBAF were explained in part by the need to harden the facility to protect against tornadoes. Considera- tion of the pros and cons of these costs is beyond the scope of this study; how- ever, it is apparent that further consideration of the potential risks and benefits associated with extensive hardening of the proposed facility may be warranted as requirements and alternatives are considered.

82 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE Before turning to a summary of the pros and cons of the NBAF as designed, the committee again notes that it was explicitly outside its scope to consider the location of the proposed NBAF in its discussions and conclusions. Advantages and Liabilities of Option 1: The National Bio- and Agro-Defense Facility as Currently Designed The currently designed NBAF has both advantages and liabilities. These are briefly discussed here and summarized in the two lists below. Because it was designed with the ideal system in mind, the proposed NBAF consolidates all components in a single location and has been designed to meet the current missions of DHS, ARS, and APHIS and proposed mission expan- sions by these agencies. For example, ARS expects to expand its research be- yond foot-and-mouth disease, CSF, and ASF to other zoonotic and emerging pathogens, including vector-borne diseases. APHIS expects to provide enhanced diagnostic services and reference materials for emerging and zoonotic diseases and relevant training. DHS expects to expand its research programs on the de- velopment of new foot-and-mouth disease vaccines and of new countermeasures for other high-priority FADs and zoonotic diseases. BSL-3Ag and ABSL-4 facilities for large-animal research are extremely limited. Most facilities that have high-biocontainment laboratory infrastructure are capable of handling small animals, and some can handle nonhuman primates and possibly medium-size animals (such as sheep and pigs) but not large live- stock species (such as cattle and horses). The proposed NBAF provides for such BSL3-Ag and ABSL-4 capacity, which is part of the infrastructure needed to achieve an integrated system to address FAD and zoonotic disease threats. In providing that capacity in the United States, the proposed NBAF does not re- quire the United States to leverage large-animal laboratory capacity through international partners whose priorities and needs may well take precedence over US priorities in the event of an outbreak that requires ABSL-4 containment. Such an outbreak is likely to attract worldwide attention and to impose immedi- ate demands on existing facilities. Finally, by including the components of the ideal system and a variety of biocontainment levels and types of laboratory in- frastructure in a consolidated facility, the proposed NBAF avoids the need to move specimens or materials derived from specimens, some or all of which will be select agents, to other facilities. Such specimens may be from experimentally infected animals, suspect FAD samples, forensic samples, or samples from ani- mals infected with unknown agents. Those overall advantages and liabilities are summarized in the lists of bulleted items below. Advantages  Includes all laboratory components of the ideal system (as identified in Figure 4-1 and Table 4-1) in a single location.

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 83  Meets current and expected future mission needs of DHS, ARS, and APHIS.  Creates needed BSL-3Ag and ABSL-4 large-animal space.  Provides the United States with in-country infrastructure to address FAD and zoonotic disease threats.  Avoids need for movement of specimens or materials derived from specimens to other facilities.  Avoids need to rely on partner entities in the United States or other countries.  Could function as part of an integrated national strategy that also in- cludes distributed and collaborative partnerships. Liabilities  Has substantial costs associated with construction.  Has substantial costs associated with continued operation and mainte- nance.  Has substantial costs associated with expanded program development.  Has potential for duplication of resources that could be reduced by ex- ploring partnerships.  Does not fully leverage existing complementary investments. An additional consideration discussed by the committee is the extent to which priorities and available technologies may change in the approximate dec- ade until an NBAF facility could be constructed and commissioned. A funda- mental question is what the workload and associated high-biocontainment space needs will be 10 or more years from now and what technology will be available to achieve research goals. If live large-animal trials for foot-and-mouth disease vaccine development are not being done, space needs may be quite different and possibly much less than the current facility design. As next-generation genetic- sequencing task times and costs decline and there are growing databases of ref- erence genomes, the use of nucleic acid-based detection and diagnostic tests will continue to expand. In most procedures, the requirement for extracting nucleic acid itself will inactivate the agent under study. As a result, the laboratory ca- pacity for agent replication in vitro may be less than what is currently needed for detecting and identifying a pathogen. The committee recognizes that current regulations require isolation of an agent for confirmatory diagnosis and that maintaining some capacity and capability for isolation of replicating agents is necessary.

84 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE ANALYSIS OF OPTION 2: A NATIONAL BIO- AND AGRO-DEFENSE FACILITY OF REDUCED SIZE AND SCOPE Envisioning a National Bio- and Agro-Defense Facility of Reduced Size and Scope The committee emphasizes that laboratory infrastructure at BSL-2, BSL-3E, BSL-3Ag, BSL-4, and ABSL-4 levels includes critical core components that must remain as part of an integrated system and that are currently a part of the proposed NBAF. However, in looking at Option 2 in the statement of task, the committee considered whether an NBAF of reduced size and scope could be designed that would address the critical gaps identified in Chapter 3 while con- tinuing to provide the United States with a comprehensive system to address FAD and zoonotic disease threats. Tables 3-1 and 3-2 list many of the US and international laboratories that have BSL-3Ag and BSL-4 capacity, which may provide opportunities for partnerships to supplement NBAF capacity. Relevant collaborations could include  In vitro diagnostic work conducted in National Animal Health Labora- tory Network (NAHLN) laboratories, in the National Veterinary Services Labo- ratories (NVSL), and in other federal laboratories, at BSL-2, BSL-3, and BSL- 3E containment.  FAD work (in vitro and in vivo) at the National Centers for Animal Health-NVSL, the Southeast Poultry Research Laboratory (SEPRL), state labo- ratories (such as the BRI), and some university facilities.  Special-pathogens in vitro work in other federal and academic BSL-4 laboratories.  In vitro vaccine development work at universities with challenge work as required at federal laboratories, including NBAF for at least FMDv.  Training at the NBAF on FMDv with some capability for animal dem- onstration teaching modules at NVSL in Ames, Iowa or at the BRI facility in Manhattan, Kansas. With the exception of FMDv, the BRI facility has appropri- ate biocontainment for animal inoculation demonstrations.  Foot-and-mouth disease work—planned only at the NBAF as the sole site in the United States that may be approved to work with FMDv. The committee identified several components of the NBAF as designed that potentially could be reduced or eliminated if such partnerships were used to meet the needs of an ideal system. They are outlined in red in Figure 4-2 as only one example of what could be considered. Although the committee provides this example of a design modification that could be made for scaling down the facil- ity while still providing critical capabilities for research and diagnostics, a de- tailed analysis of design specifications and costs was beyond the committee’s task and would need to be undertaken by the Department of Homeland Security (DHS) and the NBAF Design Partnership.

FIGURE 4-2 Re-envisioned NBAF of reduced size and scope, focusing on critical core components for which capacity cannot be effectively provided at other locations. NBAF design plans provided to committee are at 65% phase completion. Areas outlined in red are those that the committee suggests could be eliminated or reduced in scope. SOURCE: Adapted from Johnson and Barrett, 2012. 85

86 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE Examples of the areas that the committee suggests could be considered for reduction or elimination from the proposed NBAF are the Biotechnology Devel- opment Module (BDM) and the BSL-3Ag rooms designated for training along with the associated training necropsy room. Other areas that could be considered for reduction are the BSL-3Ag animal rooms, the ABSL-4 small-animal rooms, and the associated BSL-3E and BSL-4 laboratory space. Both the pilot vaccine production work conducted in the BDM, which is outside the biocontainment envelope, and most teaching and training activities could be conducted in collaboration with facilities in other US federal laborato- ries, state laboratories, universities, and the private sector. This would include options for hands-on training as well as other approaches, although US-based hands-on training on foot-and-mouth disease would of necessity be limited to the one facility designated by the Secretary of Agriculture for working with FMDv. Table 4-1 identifies some of the types of facilities that could accommo- date components of the current NBAF design, and Box 3-2 discusses approaches to training the veterinary workforce in FADs. BSL-2 laboratory support space is required for in vitro research and devel- opment, including diagnostics. Although the NAHLN provides important diag- nostic capacity to the country, an effective system to address FAD and zoonotic disease threats will nevertheless require that a central facility, such as the NBAF, support the network through confirmatory and reference diagnostics, reference reagent production, proficiency testing, and assay development. Rela- tive to the size and scope of the facility, there does not appear to be an excess of BSL-2 capacity. As a result, the committee concludes that BSL-2 space should not be reduced. BSL-3E space is similarly required. The committee noted that laboratories in the current design are designated by individual agency (DHS, ARS, and APHIS). It might be possible to reduce space needs by designating use of BSL- 3E space by function or common equipment needs or by particular agent being studied, rather than by agency, to avoid duplication. The proposed elimination of the NBAF teaching and training rooms reduces the proposed space at BSL-3Ag. However, the committee suggests that further modifications of and reductions in BSL-3Ag space might be possible, eliminat- ing one additional corridor (containing one room of type C and two rooms of type B, as shown in Figure 4-2). The block of large-animal rooms (room types B, C, and D) is designed primarily to enable large numbers of agricultural ani- mals to be housed together for animal inoculation experiments and vaccine effi- cacy trials. Although it is not ideal, the committee suggests that it might be pos- sible to conduct such trials by using a smaller number of animals simultaneously per trial, conducting sequential trials, or connecting adjacent rooms (such as rooms of type B) to form a larger space. The committee also notes that regula- tions for the emergency licensing of vaccines provide flexibility in conducting postvaccination animal-challenge studies, which can reduce the number of ani- mals per trial and thus the size of isolation rooms needed for trials. It could be argued that between flexibility in the regulations on efficacy studies of new

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 87 emergency-use animal vaccines and advances in the development of in vitro methods for evaluating vaccine efficacy, the current NBAF building design, although ideal for large-animal vaccine trials, could be modified to make use of smaller animal rooms. The use of challenge-study protocols with fewer animals at a given time could reduce the construction and maintenance costs of BSL- 3Ag animal isolation rooms, reduce the potential for human injuries in dealing with large numbers of animals in confinement, and reduce the total virus load shed at once by the challenged animals. Vaccine challenge studies are discussed more thoroughly in Box 4-1. The flexibility of the rooms could be increased by increasing the number of type B rooms that could be connected as needed and reducing or eliminating rooms of types C and D, indicated by the dashed red lines in Figure 4-2. That option also takes into consideration the changing nature of disease priorities and the potential for advances in science and technology. For example, by the time the NBAF is completed and commissioned in 10 years, the focus on conducting multiple vaccine efficacy trials for foot-and-mouth dis- ease may be reduced because many new vaccines may have already been devel- oped. However, the committee also recognizes that it is important to maintain flexibility in case new high-priority pathogens emerge and new vaccine devel- opment efforts are required. Finally, the committee suggests that some additional facility reductions may be possible through reductions in size and scope of the BSL-3E Special Proce- dures section and one of the BSL-4 support laboratories. According to DHS, the BSL-3E Special Procedures area is core space that would be used for activities that generate aerosols. It is a large space whose function is not entirely clear to the committee, and it seems feasible to reduce its scope and size. Given the availability of BSL-4 space in numerous facilities in the United States that have space for conducting small-animal trials at ABSL-4, one of the ABSL-4 small- animal suites and associated laboratory space could be considered for elimina- tion. The committee noted several minor building design aspects that might also be altered or reduced in size and scope to produce cost savings. They included the possibility of reducing the angle of separation between the Auditorium wing and BSL-2 laboratory and office space, making the lobby smaller, and reducing the scale of the building landscaping. However, those types of design compo- nents are not central to the committee’s charge to evaluate options for providing the needed laboratory infrastructure for a US system to protect against FAD and zoonotic disease threats, so it did not consider them further. With the reductions in biocontainment space outlined above (elimination of the BSL-3Ag training and necropsy rooms, reduction in and modification of the large BSL-3Ag animal rooms, and consolidation of BSL-3E laboratory space), a figurative “slice” could be removed from the right side of the NBAF biocontainment zone. Along with elimination of the BDM on the left side of the building, this might simplify the redesign of the facility. The committee did not receive information that would enable it to consider the effects of such modifica- tions on the engineering components or the final cost of the facility.

88 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE BOX 4-1 Vaccine Challenge Studies The Virus-Serum-Toxin Act (VSTA; PL 430 of 1913, as amended; 21 USC 151- 158) is implemented through regulations codified under CFR 9, Chapter I, Subchapter E, Parts 101-127, enforced by the Center for Veterinary Biologics (CVB), which is a part of APHIS Veterinary Services. The principal aim of the VSTA is to ensure that biological products5 are “pure, safe, potent, and efficacious, and not to be worthless, contaminated, dangerous, or harmful” (9 CFR§101.5).6 Standards for the determina- tion of purity, safety, potency, and efficacy have been developed through the years on the basis of cooperative research undertaken by USDA-APHIS-VS-CVB and com- mercial manufacturers. Many potency and efficacy standards have been developed in the private sector (at times under patent protection) with the approval of CVB. One of the key elements in determining efficacy of a given vaccine is the estab- lishment of statistical significance of a postvaccination response and protection in the animal as claimed by the manufacturer. For example, if a vaccine is claimed to pro- tect pregnant animals from abortion, the claim needs to be statistically proven either with challenge studies in vaccinated pregnant animals or with controlled field ex- periments that use vaccinated and nonvaccinated animals exposed naturally by a sta- tistically similar pathogenic challenge. Perhaps one of the most common ways of establishing the efficacy of a vaccine is to perform experiments that include two groups: nonvaccinated animals challenged with the pathogenic agent (control group) and vaccinated animals challenged with the pathogenic agent (vaccinated group). The preferred experimental setup is to have the control and vaccinated animals housed together and to challenge all at the same time with the same infection protocol. To gain sufficient statistical significance for a challenge study, it is desirable that an experiment be done with as many animals as is practical. In the case of foot-and- mouth disease vaccine challenge studies, the World Organisation for Animal Health (OIE) recommends the use of the percentage of protection against generalized foot infection (PGP) test. In this test, 16 foot-and-mouth disease-seronegative cattle at least 6 months old “are vaccinated with a bovine dose by the route and in the volume (Continued) 5 The term biological products is defined as including “vaccines, bacterins, allergens, antibodies, antitoxins, toxoids, immunostimulants, certain cytokines, antigenic or immu- nizing components of live organisms, and diagnostic components, that are of natural or synthetic origin, or that are derived from synthesizing or altering various substances or components of substances as microorganisms, genes or genetic sequences, carbohydrates, proteins, antigens, allergens, or antibodies” (9 CFR§101.2). 6 Definitions: purity, “quality…free of extraneous micro-organisms and extraneous material (organic or inorganic)”; safety, “freedom from properties causing undue local or systemic reactions”; potency, “relative strength…as determined by test methods”; effi- cacy, “specific ability or capacity… to effect the result for which it is offered when used under the conditions recommended by the manufacturer” (9 CFR§101.5).

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 89 BOX 4-1 Continued recommended by the manufacturer. These animals and a control group of two non- vaccinated animals are challenged 4 weeks or more after vaccination…by inoculating a total of 10,000 BID50 [bovine infectious doses of the challenge strain] intradermally into at least two sites on the upper surface of the tongue. Unprotected animals show lesions at sites other than the tongue within 7 days after inoculation. Control animals must develop lesions on at least three feet; for routine prophylactic use, the vaccine should protect at least 12 animals out of 16 vaccinated” (OIE, 2008). For statistical and quality-assurance purposes, the ideal is that all challenged and control animals be housed together in the same room and that the challenge be done simultaneously to all animals with the same preparation. That is the reason for the desire to have biocontainment BSL-3Ag facilities to house at least 18 large animals in the same room for challenge studies for foot-and-mouth disease vaccines, as has been the case for the additional isolation rooms being commissioned at PIADC and in- cluded in the design of NBAF (rooms of types C and D). The VSTA includes provisions for exemptions under 9 CFR§106.1: “The Administrator may exempt any biological product from one or more of the requirements of this subchapter if he determines that such product will be used by the Department or under the supervision or control of the Department in the prevention, control or eradication of animal diseases in connection with (a) an official USDA program; or (b) an emergency animal disease situation, or (c) a USDA experimental use of the product.” Given that vaccines against FAD agents (such as FMDv) will have to be used under emergency declaration by the Secretary of Agriculture under authorities pro- vided by the Animal Health Protection Act (7 USC, Chapter 106), there should be adequate flexibility in applying the above VSTA exemption provisions to establish efficacy data for foot-and-mouth disease vaccines and other vaccines intended solely for emergency use in the United States. For example, efficacy testing for foot-and- mouth disease vaccine candidates could be done using the PPG test protocol recom- mended by the OIE and doing challenge studies in groups of nine animals at a time (one control and eight vaccinates) simultaneously or sequentially (using NBAF rooms of type B) to achieve data on the required number of 16 vaccinated-and-challenged and 2 control-and-challenged animals. Two or three smaller adjacent isolation rooms could also be connected with opening partitions so that for a given challenge case, all animals could technically be considered “within the same confined space”, as has been the case at PIADC. Closing the partitions (gasketed doors) would allow the use of individual rooms. Smaller-scale animal vaccine challenge studies are also needed for the determi- nation of potency of new vaccines. In such cases, groups of four or five animals are vaccinated with full doses and fractions of full doses (one-half, one-fourth, one-tenth, and so on) to establish the optimal concentration of antigens that elicit a protective immune response. Once potency is established, the final large-scale efficacy chal- lenge studies are conducted.

90 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE Shelling Non-Critical Components of the Currently Designed NBAF The committee also discussed the possibility of “shelling”, or partially con- structing the NBAF as designed. That might enable near-term cost savings by focusing construction on the sections of the facility that encompass the critical core functions identified by the committee and allowing later completion of other building components if future budgets and priorities allow. That possibility might realize some cost savings in the short term, but the committee concluded that it is implicitly a subset of Option 1, the currently designed NBAF, with the only difference being a deferral or partial allocation of necessary funding for construction and operation. While realizing short-term savings, this option would not result in long-term cost savings compared to Option 1. As a result, the committee did not consider this possibility in further detail, although it raises the possibility as an additional alternative that could be considered by DHS to re- duce near-term costs. Analysis of Option 2: Laboratory Capacity In an NBAF of reduced size and scope described by the committee, all bio- containment levels are retained; as a result, this option does not decrease capa- bility but rather proposes some decreases in capacity within a central laboratory. A streamlined NBAF must function as part of an overall system that maintains the critical core competencies needed to address US FAD and zoonotic disease threats. In order to accomplish this goal, a streamlined NBAF would require the formation of collaborations with existing federal, university, and private sector laboratories to supplement its capacity. As indicated in Table 4-1 and discussed above, a variety of possible options exist for meeting some of these infrastruc- ture needs. The specific arrangements of which types of supplemental capacity would be available at which potential partner institutions and the practical de- tails of how such a system would function effectively would need to be estab- lished by DHS, USDA, and other relevant federal and non-federal partners. Tak- ing the redesign steps shown in Figure 4-2 would reduce the size of the proposed facility (see Table 4-4). The committee notes that drawing on partnerships to reduce some of the potential redundancies in US laboratory capacity for address- ing FADs and zoonotic diseases raises a theoretical possibility that system ca- pacity could be overloaded or insufficient in the event of simulta-neous disease outbreaks. As a result, the US could consider maintaining memoranda of under- standing with foreign and domestic laboratories in case of an emergency.

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 91 TABLE 4-4 Approximate Facility Size and Construction Cost Reductions Estimated Gross Cost per Estimated Net Square Gross Estimated Square Footage Footage Square Construction Reductiona Reductionb Foot ($)c Cost Savings ($)d BDM 8,320 20,800 758 15,774,000 BSL-3Ag 13,481 (estimated 53,925 977 52,685,000 reduction of 25% space) BSL-3E (including 9,365 (estimated 37,360 878 32,802,000 Special Procedures reduction of 25% space) laboratory) BSL-4 2010 (estimated 8040 1,197 9,624,000 reduction of 15% space) Total 110,885,000 a Net square footage reductions were estimated in various types of laboratory space on the basis of the NBAF 65% design plan presented by DHS (Johnson and Barrett, 2012) and additional net and gross square footage laboratory information provided to the committee (DHS, 2012b); see also Table 4-5. b The difference between the net square footage and gross square footage values of the BSL-3Ag, BSL-3E, and BSL-4 laboratory components provided by DHS to the commit- tee is 4, a multiplication factor that presumably accounts for infrastructure floors above and below laboratory floors and other supporting infrastructure requirements. c Source: DHS, 2012b. d These figures should be considered general estimates only, on the basis of information given by DHS to the committee about the NBAF 65% design plans (DHS, 2012b; John- son and Barrett, 2012). The committee cannot predict exact net and gross square footage reductions associated with its proposal and is unable to account for additional costs re- lated to facility redesign and timeline adjustments or for potential cost savings from fu- ture reductions in operations costs. Analysis of Option 2: Relative Costs and Other Considerations The streamlined NBAF described above envisions a scaled-back building design. Although the committee has attempted to keep as many elements of the current building intact as feasible, pursuing this option would require at least some building redesign. On the basis of gross square footage construction cost estimates provided by DHS, an approximately 25% reduction in size of the NBAF as shown in Figure 4-2 and provided as one example could result in a construction cost savings of approximately $110 million (Table 4-4). This esti- mate is provided as a relative cost reduction only, and does not take into account the cost of redesign and delays in construction that might increase the cost as well as the additional expenses needed to continue operations of the Plum Island facility in the interim. DHS has noted that a facility redesign would need to re- turn to the 15% design stage to re-evaluate the complex mechanical, electrical, plumbing, and other engineering systems associated with biocontainment labo- ratories and that changes in the size and scope of the main laboratory building

92 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE depicted in Figure 4-2 might affect support facilities and require additional changes (DHS, 2012b). The committee recognizes that a redesign process would add construction time and costs that could offset at least some of the potential cost savings from reducing the size and scope of facility components. In its presentation to the committee, DHS estimated that a facility redesign would cost $50-60 million and add 12-18 months to the process. DHS later re- fined those estimates, using an example in which the BSL-4 component was eliminated from the main laboratory and estimating a 30-month delay due to redesign and contract procurement. At 4% annual cost increases, the result would be an overall cost increase of $177 million. The committee found that it did not have enough information to analyze that estimate objectively, but it notes that an NBAF with a smaller footprint and reductions in high- biocontainment laboratory space might have lower sustained operations costs. Other long-term cost savings may be realized by making more efficient use of the existing networks of US laboratory capacity, particularly for in vitro and small animal studies and work with zoonotic pathogens. However, additional costs of using partnerships to meet US needs for countering disease threats in- clude the costs associated with creating and maintaining the contractual ar- rangements and contract management necessary to partner with other facilities for work that would not be performed at the currently planned NBAF. Overall costs across the total federal budget would be influenced by the extent to which activities were shifted to existing federal laboratory facilities that currently have additional or under-used capacity and to non-federal facilities; total cost implica- tions are thus unknown given the information and rough estimates provided to the committee. Analyzing the actual costs of building an NBAF of reduced size and scope was beyond the scope of what the committee could address given the extremely tight schedule for the study and the limited information available. This would need to be explored further to gain a detailed understanding and es- timate. Advantages and Liabilities of Option 2: A National Bio- and Agro-Defense Facility of Reduced Size and Scope The concept of an NBAF of reduced size and scope from the current design has both advantages and liabilities. Because it would continue to incorporate laboratory infrastructure at BSL-3Ag, BSL-4, and ABSL-4, it would continue to address the critical core needs of an ideal system for dealing with FAD and zoonotic disease threats identified by the committee. It would also still allow the consolidation of mission needs of DHS, ARS, and APHIS in a single location and meet the overall needs of countering disease threats to the nation. This op- tion also makes more efficient use of the network of recently expanded US high- containment laboratory capacity and avoids some duplications of laboratory infrastructure. In addition, an NBAF of reduced size and scope, in conjunction with an integrated network of laboratories, would foster greater collaboration

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 93 between researchers and greater understanding of missions as part of the overall integrated system for countering disease threats. Finally, by relying on a net- work of partners, this option may provide increased flexibility to re-evaluate laboratory infrastructure needs periodically in light of new and emerging disease priorities and technologies. In contrast, reducing the NBAF in size and scope means that some compo- nents of the ideal system for countering FAD and zoonotic disease threats (such as teaching and training and vaccine production) are not housed in a single facil- ity and would need to be obtained in collaboration with a network of other facili- ties. Such a system may require the movement of specimens or materials derived from specimens, some of which will be select agents, to other facilities. It would also require effective coordination among the agencies involved. Current poli- cies and regulations, such as facility requirements for select-agent authorization, would need to be examined and perhaps modified. The option would also re- quire interagency cooperation in developing agreements regarding the use of laboratory space and entail a need to explore and create agreements with partner facilities. In addition, because of reductions or consolidations in space, this op- tion might require DHS and USDA to set priorities because they may not be able to expand their research programs as quickly or as widely as they have proposed and would probably need to adjust planned numbers and timelines for large- animal vaccine efficacy studies. The ultimate cost implications of Option 2 compared to Option 1 are un- clear based on the limited information provided to the committee and would need to be studied in greater detail. The overall advantages and liabilities considered by the committee are summarized in the lists of bulleted items below. Advantages  Provides an approximately 25% smaller NBAF that may have reduced construction costs (although the actual cost implications are not clear).  May provide lower sustained costs of NBAF operation; may also pro- vide some longer-term cost savings by making more efficient use of existing US laboratory infrastructure and partnerships.  Addresses critical core needs for BSL-3Ag, BSL-4, and ABSL-4.  Still allows DHS, ARS, and APHIS mission consolidation in a single lo- cation.  Meets overall needs of countering disease threats to the nation.  Provides in-country capacity.  Makes more efficient use of recently expanded US laboratory capacity.  Fosters greater collaboration and understanding between researchers as part of the integrated US system for countering FAD and zoonotic disease threats.

94 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE  Changes the approach to addressing animal diseases by drawing on sci- entific and research expertise in other federal and non-federal laboratories, pro- viding both intellectual benefits and possible cost savings through increased efficiencies by avoiding duplication or relocation of scientists at the NBAF and fostering collaboration.  Provides more flexibility for periodically re-evaluating infrastructure needs in light of new and emerging disease priorities and technologies. Liabilities  Not all components of the ideal system are housed in a single integrated facility.  May require movement of specimens or materials to other facilities.  Requires interagency cooperation in developing agreements in the use of laboratory space.  Requires creation of agreements with partner facilities.  Requires funding commitments to partner facilities for collaborative work and establishment of grant-management capacity to oversee collabora- tions.  Would have policy implications that would need to be explored further.  Might require DHS and USDA to make priority-setting decisions. ANALYSIS OF OPTION 3: MAINTAINING CURRENT CAPABILITIES AT PLUM ISLAND ANIMAL DISEASE CENTER WHILE LEVERAGING ABSL-4 LARGE-ANIMAL CAPACITY THROUGH FOREIGN LABORATORIES The third option in the statement of task to be considered by the committee was to maintain the current capacity of PIADC and to use BSL-4 and ABSL-4 large-animal facilities that are currently available at foreign laboratories. PIADC does not contain infrastructure for conducting research at BSL-4 and ABSL-4. The committee was informed by DHS that BSL-4/ABSL-4 laboratory facilities could not be constructed at PIADC; the committee therefore did not further con- sider the possibility of building BSL-4/ABSL-4 space at PIADC. Current Situation of Plum Island Animal Disease Center Capacity and Capabilities PIADC has a long history of serving the nation as the sole high- biocontainment laboratory for performing research and diagnostic investigations on foot-and-mouth disease and other FADs. A historical perspective of the role of PIADC in FAD work is presented in Appendix C. PIADC remains the only

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 95 laboratory in the United States that has the capability and capacity to address the threat of foot-and-mouth disease. The committee notes that foot-and-mouth dis- ease is appropriately still considered the highest-priority disease threat to US agriculture because of its highly contagious nature, as demonstrated by the con- tinued occurrence of foot-and-mouth disease outbreaks in many areas of the world (such as South Korea), the movement of hundreds of people and countless goods to the United States daily, the continuous movement of FMDv strains around the world (such as the appearance of SAT-2 in areas of north Africa)7, and the threat of bioterrorism with FMDv as a means of disrupting the economic and social infrastructure of the United States. It is imperative that the nation maintain an infrastructure to address countermeasures against a FMDv outbreak, whether naturally occurring or intentional. With regard to the core laboratory needs identified above and used as a framework for considering Options 1 and 2, PIADC currently provides capabil- ity and capacity for  In vitro diagnosis—maintains full range of diagnostics for confirmatory diagnosis of index cases of foot-and-mouth disease, CSF, ASF, and other FADs (it should be noted that confirmatory testing for a number of other FADs is also performed at NVSL, Ames); presumptive-level testing in outbreak investiga- tions other than priority 1 is now allowed and performed in NAHLN laborato- ries;8 some BSL-2 work is done at NVSL, Ames and at PIADC, including preparation of reference reagents and proficiency-testing support.  FAD work (in vitro and in vivo); it should be noted that work with some pathogens or species is done at NVSL, Ames and SEPRL.  Special-pathogens work, but no capacity for BSL-4/ABSL-4.  Vaccine development—some in vitro and selected challenge work; two new challenge-study rooms are being commissioned and will increase capacity.  Foot-and-mouth disease work—all done at PIADC in accordance with current laws.  Training—nearly all FAD training with animal demonstrations; some laboratory training is done at CVB in Ames, IA. The laboratory space currently available at PIADC is summarized and com- pared to the equivalent biocontainment level space in the proposed NBAF in Table 4-5. The total space available in the main buildings at PIADC is 142,700 net ft2 and 245,940 gross ft2, compared to 176,000 net ft2 and 580,200 gross ft2 available in the main building of the proposed NBAF (Johnson and Barrett, 7 SAT-2 foot-and-mouth disease virus is one of three major virus serotypes designated as South African Territories (SAT) 1-3. SAT-2 is the most common type causing foot- and-mouth disease in sub-Saharan Africa and West Africa (Bastos et al., 2003). 8 The procedures for conducting investigations of potential foreign animal diseases are outlined in Veterinary Services Memorandum 580.4 (USDA, 2010).

96 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE 2012). The committee notes that the condition and functionality of the space are also important considerations beyond a direct comparison of square footage. TABLE 4-5 Comparison of Space Available at PIADC and the Proposed NBAF Space available at Space available at proposed PIADC (net square feet) NBAF (net square feet) BSL-4 laboratories 0 13,400 BSL-3Ag and BSL-3E 72,400 81,100a laboratories BSL-2 laboratories 5,300 9,700 BSL-2 Biotechnology 0 8,300 Development Module Office and support space 65,000 63,500 SOURCE: Johnson and Barrett, 2012. a The proposed NBAF includes 37,460 net ft2 of BSL-3E and 53,925 net ft2 of BSL-3Ag laboratory space (including animal support), which totals 91,385 net ft2 (DHS, 2012b). The approximately 10,285 net ft2 difference between this total and the 81,100 net ft2 listed above presumably represents the animal support component. Land, buildings, and other facilities of PIADC were transferred to DHS in June 2003. Since then, the DHS Science and Technology Directorate has been responsible for operating and maintaining the Plum Island site. Operational ser- vices—including security, building and site maintenance, and operation of ma- rine vessels and transportation—are contracted out to an independent private organization. DHS provides the director of PIADC. ARS and APHIS have es- tablished agreements with DHS for their continued operations at PIADC, and each provides a director for its research and diagnostic programs. Each USDA agency is responsible for providing its own scientific and technical support staff and for paying for its own scientific operations (cost of diagnostic operations or cost of bench and animal research activities). Analysis of Option 3: Laboratory Capacity PIADC has been able to provide the basic facilities for research, diagnosis, and training needed for the protection of the United States against FADs for more than 50 years, but there are several important limitations in its laboratory capacity. Some remodeling of the main biocontainment building, Building 101 (now approaching 60 years old), was done in 1994, and the building of two new animal holding rooms and the remodeling of one necropsy room have provided needed additional space for current work. However, the basic building structure, the size of the animal rooms, and other ancillary infrastructures are seriously deficient for state-of-the-art research and diagnostic work at high biocontain-

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 97 ment. The building does not meet current standards for BSL-3Ag and does not have capabilities for BSL-4 and ABSL-4. All physical support for the building— such as high-efficiency particulate air filters, heating, ventilation, and air- conditioning—is within the biocontainment envelope, where maintenance and repairs are more difficult, expensive, and time-consuming. PIADC requires con- tinuing high annual operating costs and will continue to need renovations. Fi- nally, as noted above, the committee was advised that adding BSL-4/ABLS-4 containment to PIADC was not possible, given the need for political and local acceptance to conduct such work on Plum Island. If this is correct, the building cannot meet all the components of an ideal system as identified by the commit- tee. The need for replacement facilities and the decommissioning of existing buildings were noted in the previous studies of the facility and in the recent 2006 DHS decision to build the NBAF on the US mainland (NRC, 1983; USDA, 1994, 1999; DHS, 2008b; 74 Federal Register, 2009). Pursuing Option 3 would therefore require the United States to seek ABSL- 4 large-animal laboratory capacity through partners such as foreign laboratories. BSL-4 capabilities for in vitro and small-animal work exist at current facilities in the United States and abroad.9 The United States lacks ABSL-4 large-animal capacity, and such capacity is extremely limited in the entire Western Hemi- sphere (only the facility in Winnipeg, Canada has the capacity for ABSL-4 work in livestock, and this facility is small). Option 3 would require the United States to obtain this capacity, when it is needed, through partnerships with foreign laboratories; Table 3-2 identifies some of the international facilities that have ABSL-4 capabilities. Despite the limitations noted above, the committee emphasizes here and elsewhere in this report that the facilities available at PIADC must be main- tained until a new US biocontainment facility is constructed and commissioned. The committee also believes that, given the current lack of US ABSL-4 facilities that could handle large animals, it is advisable for the United States to enter into formal cooperative agreements now with foreign laboratories to conduct re- search that may require ABSL-4 large-animal containment. Such agreements could be established in the interim until a new US biocontainment facility with ABSL-4 large-animal space is built and commissioned. As indicated in the his- tory of PIADC (Appendix C), successful international research cooperative agreements existed before the creation of PIADC to work with FMDv in several European laboratories, and this model could be replicated for the emergency use of ABSL-4 facilities until this critical capacity is available in the United States or as an emergency supplement to future US ABSL-4 large-animal capacity. 9 As indicated above, the committee does not agree with USDA and DHS statements that BSL-4 capabilities are required for unpacking diagnostic samples or for basic diag- nostic procedures when nucleic acid detection technologies are used. Such work can be and is performed safely in regular BSL-3 or BSL-3E facilities.

98 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE Relative Costs Annual PIADC operating costs in FY 2020 are estimated at $56 million ($50 million for operations and maintenance, $6 million for DHS salaries). That does not include the salaries and operations of ARS and APHIS personnel and programs at PIADC. However, the aging PIADC facilities are in need of sub- stantial improvements. Initial rough estimates total $90 million for short-term improvements (including improvements in the liquid-waste decontamination facility, Plum Island and Orient Point Harbors, information technology up- grades, utility and building upgrades, security hardening, detection and access control, and marine-vessel replacement and lighthouse restoration), while long- term improvements are estimated at $210 million if PIADC is required to main- tain its existing mission and to continue operating for another 25 years. Advantages and Liabilities of Option 3: The Plum Island Animal Disease Center PIADC is currently the only US facility that can provide several of the criti- cal core functions of an integrated system to address FAD and zoonotic disease threats and is the only laboratory in the United States that is authorized to con- duct research, diagnostics, and training related to foot-and-mouth disease. It represents an existing investment that would avoid the costs of construction of a new biocontainment facility. If a full commitment were made to improving and maintaining PIADC, the avoidance of constructing a new facility would also obviate the need for a facility transition period with a potential temporary loss of function. In addition, capital improvements and other investments are needed at PIADC over the next 10 years, whether the facility is maintained only until a new facility is constructed or continues to serve as the central laboratory for a US system to address FADs and zoonotic diseases over a longer period. Thus, pursuing Option 3 would continue to realize the benefit of those investments over a longer period. It would also exclude the risk that necessary investments are being forgone to save costs during the years just before PIADC cedes its activities to a new NBAF. By relying on the ABSL-4 capacity of other existing US laboratories (for in vitro and small-animal work) or foreign partners (for ABSL-4 large-animal work), this option also saves the United States from in- vesting in in-country BSL-4/ABSL-4 capacity. Cooperative agreements with foreign partners in case of an ABSL-4 need also enhance international coopera- tion in FAD and zoonotic disease research. In contrast, continuing to maintain and operate PIADC even without reno- vation entails substantial annual costs of about $60-90 million. The facilities at PIADC are aging and do not meet current standards for high-biocontainment laboratories, including the 2004 Homeland Security Presidential Directive 9 [HSPD-9 (2004)] mandate to build new biocontainment facilities. Under Option

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 99 3, the United States would not have a modern biocontainment facility for FAD research, particularly research on foot-and-mouth disease, and would not have ABSL-4 capacity. The need to rely on foreign partners for ABSL-4 large-animal capacity might limit the availability of such capacity in a time of emergency if US needs were considered secondary to the needs and priorities of the partner country. Finally, the long-term maintenance of PIADC will continue to experi- ence difficulties in hiring new high-level scientists to work there; this is a chal- lenge because of the aging infrastructure and the remote location. The commit- tee did not further consider this or other site-specific issues as site was prohibited from consideration in the statement of task. The overall advantages and liabilities considered by the committee are summarized in the lists of bulleted items below. Advantages  Is an existing US facility that provides many of the laboratory infra- structure components needed and would avoid the costs of constructing a new replacement facility.  Is the only US facility that is authorized to conduct research, diagnos- tics, and training in foot-and-mouth disease.  If there were a full commitment to PIADC, a transition period to a new facility with a window of potential loss of function would not be needed.  Realizes the benefits of the capital renovations and improvements that must be made for a longer period.  Does not require investment in BSL-4/ABSL-4 capabilities in the United States.  Could function as part of an integrated national system that also in- cludes distributed and collaborative partnerships  Enhances international cooperation for work on FADs and emerging animal and zoonotic diseases. Liabilities  Has a high cost to maintain and operate PIADC.  Does not provide the United States with a modern biocontainment fa- cility for FAD and zoonotic disease research, particularly on foot-and-mouth disease.  Does not provide the United States with BSL-4/ABSL-4 capability for handling large animals.  Requires establishing agreements with foreign partners for access to BSL-4 laboratories and presumably funding to support the collaborations.

100 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE  May limit the availability of BSL-4 capabilities in times of need, de- pending on priorities of other countries.  Continues to highly limit ABSL-4 large-animal capacity in the Ameri- cas.  Maintaining PIADC long term will continue to compound the difficul- ties in hiring new high-level scientists to work there due to the continued isola- tion of the national laboratory site from academic and other research and devel- opment centers. CONCLUSIONS ABOUT THE THREE OPTIONS As a result of its evaluation of the three options in its statement of task, the committee finds  Option 1: The NBAF as currently designed includes all components of the ideal laboratory infrastructure in a single location and has been designed to meet the current and anticipated future mission needs of DHS, ARS, and APHIS; but the proposed facility also has drawbacks (Conclusion 1).  Option 2: A partnership of a central national laboratory of reduced scope and size and a distributed laboratory network can effectively protect the United States from FADs and zoonotic diseases, potentially realize cost savings, reduce redundancies while increasing efficiencies, and enhance the cohesiveness of a national system of biocontainment laboratories. However, given the limited and insufficient information provided by DHS, the cost implications of reducing the scope and capacity of a central facility cannot be known without further in- formation and study (Conclusion 2).  Option 3: Maintaining PIADC and drawing on the ABSL-4 large-animal capacity of other partners would utilize an existing US facility that provides some of the needed laboratory infrastructure components and would avoid the costs of constructing a new replacement facility. However, the facilities at PIADC are aging and do not meet current standards for high-biocontainment laboratories, there are substantial costs associated with maintaining and operat- ing it, it lacks BSL-4 and ABSL-4 large-animal capabilities, and the committee was informed by DHS that such facilities could not be constructed at PIADC (Conclusion 3). OTHER OPTIONS The committee recognizes that the three options it was asked to address in the statement of task are not the only possible options for meeting the nation’s laboratory infrastructure needs with regard to animal and public health. For ex- ample, the possibility of constructing BSL-4/ABSL-4 space on Plum Island could be revisited; the option of constructing an entirely new laboratory facility

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 101 on Plum Island, perhaps connected to the mainland by a bridge, could be con- sidered; NBAF could be built only as a replacement for the existing facility on Plum Island, with newly constructed ABSL-4 large-animal space co-located with existing ABSL-4 laboratory space now used to study zoonotic diseases in small animals and primates; or a variety of other options. As a result, the com- mittee notes that there are numerous possibilities for creating an integrated na- tional strategy and a network of collaborative partnerships to achieve the ideal system for addressing FAD and zoonotic disease threats. However, evaluating the full array of options and their relative advantages and disadvantages funda- mentally draws not only on infrastructure needs but also on discussions of site locations, risk assessments, political considerations, adaptability for the future, and other elements explicitly outside of the committee’s statement of task, as- pects of which have also been the subject of previous reports. SUMMARY In this chapter, the committee has described how an NBAF of reduced size and scope might be envisioned and has discussed the advantages and liabilities of the three options that it was asked to consider in its statement of task. On the basis of the committee’s research and discussions, Chapter 5 provides the com- mittee’s additional conclusions and recommendation on how the laboratory re- search needed to enable the United States to address FADs and zoonotic dis- eases might be effectively assembled. REFERENCES ASTMH (American Society of Tropical Medicine and Hygiene). 2003. The American Committee of Medical Entomology Arthropod Containment Guideline (Version 3.1). Vector Borne and Zoonotic Diseases 3(2):57-98. Bastos, A.D., D.T. Haydon, O. Sangaré, C.I. Boshoff, J.L. Edrich, and G.R. Thomson. 2003. The implications of virus diversity within the SAT 2 serotype for control of foot- and-mouth disease in sub-Saharan Africa. Journal of General Virology 84:1595-1606. CDC (Centers for Disease Control and Prevention). 2009. Biosafety in Microbiological and Biomedical Laboratories (BMBL), 5th Ed. (CDC) 21-1112. US Department of Health and Human Services, Public Health Services, Centers of Disease Control, National Institute of Health [online]. Available: http://www.cdc.gov/biosafety/public cations/bmbl5/BMBL.pdf (accessed June 5, 2012). CRS (Congressional Report Service). 2008. The National Bio- and Agro-Defense Facil- ity: Issues for Congress. Updated November 25, 2008. Order Code RL34160. Colby, M. 2012. DHS Science Program. Presentation at the Meeting on an Analysis of the Requirements and Alternatives for Foreign Animal and Zoonotic Disease Re- search and Diagnostic Laboratory Capabilities, April 13, 2012, Washington, DC. DHS (Department of Homeland Security). 2007a. Additional Physical, System, and Man- agement Controls Can Enhance Security at Plum Island (Redacted). OIG-07-43. US Department of Homeland Security, Office of Inspector General.

102 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE DHS. 2007b. Final Selection Memorandum For Site Selection for the Second Round Potential Sites for the National Bio and Agro-Defense Facility (NBAF). July 2007. US Department of Homeland Security, Science and Technology Directorate. DHS. 2008a. An Addendum to the Final Selection Memorandum for the Site Selection for the Second Round Potential Sites for the National Bio and Agro-Defense Facility (NBAF), Dated July 2007. Memorandum for the Record. US Department of Home- land Security, Science and Technology Directorate. DHS. 2008b. National Bio and Agro-Defense Facility: Final Environmental Impact Statement. December 2008. US Department of Homeland Security, Science and Technology Directorate, Office of National Laboratories. DHS. 2012a. NBAF Updated Site-Specific Biosafety and Biosecurity Mitigation Risk As- sessment. Final Report, Vol. 1, February 2012 [online]. Available: http://www.dhs. gov/xlibrary/assets/st/nbaf_updated_ssra_volume_i.pdf (accessed May 30, 2012). DHS. 2012b. DHS Responses and Supporting Materials to the Questions Sent by the Committee. April 20, 2012. Federal Register. 2009. Record of Decision for the National Bio and Agro-Defense Facil- ity Environmental Impact Statement. US Department of Homeland Security, Science and Technology Directorate. Washington, DC: US Government Printing Office. 74(11):3065-3080 [online]. Available: http://edocket.access.gpo.gov/2009/E9- 914.htm (accessed June 5, 2012). Johnson, J., and L. Barrett. 2012. PIADC & NBAF. Presentation at the Meeting on an Analysis of the Requirements and Alternatives for Foreign Animal and Zoonotic Disease Research and Diagnostic Laboratory Capabilities, April 13, 2012, Washing- ton, DC. Kappes, S. 2012. ARS Science Program. Presentation at the Meeting on an Analysis of the Requirements and Alternatives for Foreign Animal and Zoonotic Disease Re- search and Diagnostic Laboratory Capabilities, April 13, 2012, Washington, DC. Lautner, E. 2012. APHIS Science Program. Presentation at the Meeting on an Analysis of the Requirements and Alternatives for Foreign Animal and Zoonotic Disease Re- search and Diagnostic Laboratory Capabilities, April 13, 2012, Washington, DC. Mettenleiter, T.C. 2012. Welcome to the Friedrich-Loeffler-Institut Federal Research Institute for Animal Health. Presentation at the Meeting on an Analysis of the Re- quirements and Alternatives for Foreign Animal and Zoonotic Disease Research and Diagnostic Laboratory Capabilities, April 13, 2012, Washington, DC. NDP (National Bio- and Agro-Defense Facility Design Partnership). 2011. 50% Con- struction Documents, Basis of Design, August 19, 2011 (as cited in DHS, 2012a). NRC (National Research Council). 1983. Long-Term Planning for Research and Diagno- sis to Protect US Agriculture from Foreign Animal Diseases and Ectoparasites. Washington, DC: National Academies Press. NRC. 2005. Critical Needs for Research in Veterinary Science. Washington, DC: The National Academies Press. OIE (World Organisation for Animal Health). 2008. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (mammals, birds and bees). 6th edition. Version adopted by the World Assembly of Delegates of the OIE in May 2009. Paris: Office International des Epizooties. USDA (US Department of Agriculture). 1994. Final Report: Task Force on Biocontain- ment Facilities for Foreign Animal Disease Research and Diagnostic Activities. Ag- riculture Research Service (ARS) and Animal and Plant Health Inspection Service (APHIS). March, 1994.

ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 103 USDA. 1999. Report of the Strategic Planning Task Force on USDA Research Facilities: A 10-year Strategic Plan. Report and Recommendations. Washington, DC: US Gov- ernment Printing Office. USDA. 2010. Veterinary Services Memorandum No. 580.4. Procedures for the Investiga- tion of Potential Foreign Animal Disease/Emerging Disease Incidents (FAD/EDI). John R. Clifford, Deputy Administrator, Veterinary Services, August 18, 2010.

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Outbreaks of animal disease can have catastrophic repercussions for animal agriculture, the food supply, and public health. Rapid detection, diagnosis and response, as well as development of new vaccines, are central to mitigating the impact of disease outbreaks. The proposed National Bio- and Agro-Defense Facility (NBAF) is a next-generation laboratory for animal disease diagnostics, training, and research that would provide core critical components for defense against foreign animal and zoonotic disease threats. But it will be a major investment with estimated construction costs of $1.14 billion, as currently designed.

Meeting Critical Laboratory Needs for Animal Agriculture: Examination of Three Optionsdiscusses the laboratory infrastructure needed to effectively address the threat posed by animal and zoonotic diseases and analyzes three options for creating this infrastructure: building NBAF as currently designed, building a scaled-back version of the NBAF, or maintaining current research capabilities at Plum Island Animal Disease Center while leveraging biosafety level-4 large animal capabilities at foreign laboratories.

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