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 foreign 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 incorporates the critical core functions of disease surveillance, diagnostics, outbreak response and recovery, research and development, and workforce training described earlier in this report, as well as expected future needs (see Chapter 3). Successful implementation of those critical systemwide functions requires practical 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 disease 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, regardless of the option considered for the central laboratory facility. In subsequent sections, the committee discusses the three options and assesses how they address capacity needs, such factors as relative costs, and other considerations.



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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

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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.

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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

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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).

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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 Option 3 NBAF PIADC 1 2 Option 2 NAHLN, RBL/NBL, 1 2 Private Sector Streamlined 3 3 6 NBAF 1 3 3 5 6 4 2 54 3 Academe Academe 1 5 5 1 6 4 Academe, 6 NAHLN, RBL/NBL, NAHLN 4 5 Private Sector, RBL/NBL, Private Sector Academe National BSL-4 Labs, Academe, NAHLN 4 International BSL-4 Labs 6 National BSL-4 Labs, 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

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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).

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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.

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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.

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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-3Ag BSL-3 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

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76 TABLE 4-1 Continued RBL/NBL Private National International NBAF as NBAF- BSL-3 BSL-3Ag Sector BSL-4 BSL-4 Designed Streamlined Laboratories Academe Laboratories Laboratories Laboratories Components NAHLN 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.

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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

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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

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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).

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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 81,100a BSL-3Ag and BSL-3E 72,400 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. The proposed NBAF includes 37,460 net ft2 of BSL-3E and 53,925 net ft2 of BSL-3Ag a 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-

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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.

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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

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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.

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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

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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.

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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.

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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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