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Executive Summary T he biodefense efforts of the Department of Defense (DoD) are poorly organized to develop and license vaccines, therapeutic drugs, and antitoxins to protect members of the armed forces against biological warfare agents. These efforts are characterized by fragmentation of responsibility and authority, changing strategies that have resulted in lost time and exper- tise, and a lack of financial commitment commensurate with the require- ments of program goals. These factors, together with special regulatory challenges for obtaining Food and Drug Administration (FDA) approval of biowarfare countermeasures,1 mean that since the Gulf War of 1990 1991 DoD has gained no new vaccines and only a few drugs as medical biodefense countermeasures. This serious situation exists despite declarations that biological war- fare poses a significant threat to the safety and effectiveness of the nation's armed forces (Bush, 2002; Cohen, 1997; Defense Science Board, 2001, 2002; Perry, 1996; U.S. Congress, House Armed Services Committee, 1993), the recent vaccination of large numbers of military personnel against anthrax and smallpox, a DoD commitment to acquire vaccines against all vali- 1It was not possible to license new vaccines or drugs against biological warfare agents until July 2002, when the FDA's "Animal Efficacy Rule" became effective (FDA, 2002). The Animal Efficacy Rule allows the use of efficacy data from animal studies when tests of effi- cacy in humans are not ethical or feasible, as is generally the case with medical biodefense countermeasures. 1

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2 GIVING FULL MEASURE TO COUNTERMEASURES dated biological warfare threats (DoD, 1993), and concerns about new bioengineered microbial threats. The development and licensure of new vaccines and drugs is a diffi- cult, expensive, and time-consuming process. Moreover, biodefense prod- ucts pose special scientific, regulatory, and ethical challenges because it is generally unacceptable to expose humans to biowarfare agents to estab- lish the efficacy of those products. Accelerating the development and li- censure of such products will require strong and creative scientific leader- ship and a sustained commitment of adequate financial and other resources. This report presents the findings and recommendations of a commit- tee of the Institute of Medicine (IOM) and the National Research Council (NRC) convened to conduct a study mandated by Congress. The charge to the committee is to recommend strategies for accelerating the DoD re- search, development, and licensure processes for new medical biodefense countermeasures.2,3 Based on the study charge to address strategies for accelerating these processes, the committee focused its attention on the organization and management of these processes, rather than on details of specific scientific approaches. The committee was not asked to assess the nature or extent of any biological warfare threat or to compare the value to DoD of developing medical countermeasures against biological warfare agents relative to the pursuit of its other obligations. The committee viewed its task as resting on the premise that biological weapons pose a genuine threat to the health of military personnel, and therefore additional FDA-licensed medical countermeasures are urgently needed. THE CURRENT CONTEXT Scientific and technological developments are expanding the range of potential biological threats as well as opening pathways to new counter- measures. Meanwhile the need continues for work on countermeasures currently in development pipelines to protect against more familiar bio- logical threats. For decades, DoD carried out the only significant effort in medical biodefense countermeasure development. Now, however, a sub- stantial biodefense research effort is under way within the Department of 2The study was called for in the National Defense Authorization Act for Fiscal Year 2002 (P.L. 107-107). The study charge, the expertise of the committee, and the committee's ap- proach to the study are discussed in the Preface. 3In this report, the term "licensed" is used to connote approval by the FDA of either a Biologics License Application or New Drug Application.

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EXECUTIVE SUMMARY 3 Health and Human Services (DHHS), with funding of $1.7 billion allo- cated to the National Institutes of Health (NIH) for fiscal year (FY) 2003 (and $1.6 billion requested for FY 2004) (DHHS, no date). In addition, a proposal for "Project BioShield" aims to create incentives for the pharma- ceutical industry to manufacture and license medical countermeasures by making up to $6 billion dollars available over the next 10 years to pur- chase those products for a national stockpile (White House, 2003). In con- trast, DoD's funding for its research and development program for medi- cal countermeasures against at least 10 biological agents amounts to only $267 million for FY 2003 (DoD, 2003; Evans, 2003).4 The upsurge in funding and effort aimed at protecting the civilian population against bioterrorism will undoubtedly result in the develop- ment of new technologies and products that can also aid in protecting military personnel against the risks of biological warfare. However, the perceived risks posed by these agents can be different in the two settings, and there are important differences between the planning for protection against bioterrorism and biological warfare (DoD, 1993, 2000; Fauci, 2003; Linden, 2002). The military has considered vaccination to be the primary medical strategy for battlefield protection of a defined and relatively small population. Mass vaccination of the civilian population against a range of potential biological threats is less appropriate and much less feasible. For DoD, the aim is to protect service members in a manner that allows them to maintain their combat effectiveness and limits the need for medical personnel and equipment to treat casualties. Having the capacity for rapid diagnosis and postexposure treatment is also essential for DoD, but it is less desirable as a primary strategy for protecting troops on the battlefield than it is for responding to a bioterrorism event in the civilian population. The challenges in developing new vaccines and drugs include the cost of the process and the substantial risk of failure. The congressional Office of Technology Assessment (OTA) in 1993 estimated the average cost of bringing a new drug to licensure to be $237 million (1990 dollars) (U.S. Congress, OTA, 1993). More recent estimates have ranged from $110 mil- lion to $802 million (2000 dollars) (DiMasi et al., 2003; Public Citizen, 2001). As few as one candidate in 5,000 reaches clinical testing, and only 20 per- cent of candidates that begin clinical testing reach licensure (FDA, 1999; 4The DoD funding for FY 2003 includes program elements for medical biological defense in the Chemical and Biological Defense Program (under budget activities 6.16.5) and bio- medical components of the biological warfare defense program of the Defense Advanced Research Projects Agency (DARPA). The funding totals for medical biodefense exclude costs presently covered in accounts of the military services for salaries and benefits for military personnel and for operating certain facilities.

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4 GIVING FULL MEASURE TO COUNTERMEASURES NVAC, 1999; PhRMA, 2000; Struck, 1996). Such estimates are based pri- marily on data for new drugs; equivalent estimates for vaccines and other biologics are rarely presented (IOM, 2003). The process is also time consuming, with an industry estimate of 7 to 12 years for vaccine development, but with past experience showing that successful completion of clinical testing alone can take as long as 20 years (Grant, 2003; NVAC, 1999). New techniques are likely to speed the dis- covery of some candidate countermeasures, but are unlikely to accelerate some of the most time-consuming parts of the product development pro- cess, including the crucial assessment of product safety in human volun- teers and efficacy based on animal data under new FDA regulatory guide- lines (the "Animal Efficacy Rule") (FDA, 2002). The use of animal-based efficacy testing for products intended to protect against potentially lethal pathogens for which efficacy studies in humans are not feasible or ethical is still a new process and likely to require considerable time and effort to become regularized. PROBLEMS WITH THE DOD EFFORT The committee sees dismal prospects for successful results (and no prospects for faster results) from the current efforts by DoD's Chemical and Biological Defense Program to produce medical biodefense counter- measures. This task has not been given sufficient priority by DoD to pro- duce the intended results. Furthermore, the disjointed and ineffective management and inadequate funding of current efforts are clear indica- tions that DoD leaders lack an adequate grasp of the commitment, time, scientific expertise, organizational structure, and financial resources re- quired for success in developing vaccines and other pharmaceutical prod- ucts. Developing these products is a difficult endeavor, even with strong leadership and adequate resources. The fragmented half-measures of DoD's current effort cannot be expected to succeed. RECOMMENDATIONS FOR ACTION Maintaining the status quo in DoD only assures a long, costly, and perhaps fruitless wait for new vaccines and therapeutic products. The successful development and licensure of new countermeasures to protect against present and future biological warfare threats require a substantial and sustained effort, including having strong, scientifically knowledge- able leadership and adequate funding. To help ensure that DoD has an effective program to develop medical biodefense countermeasures to meet its unique needs, the committee makes recommendations in three areas:

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EXECUTIVE SUMMARY 5 1. Making the program a genuine priority 2. Establishing a sound infrastructure to support the program 3. Addressing other challenges related to the development of medi- cal countermeasures Key recommendations are discussed below, and the complete set of recommendations appears in Box ES-1 at the end of this chapter. Making the Development of Medical Countermeasures a Priority A decision by DoD and national leaders to make the DoD program to develop medical countermeasures against biological warfare agents a genuine priority is the essential first step to set the stage for an effective program aimed at meeting unique DoD needs. To ensure that DoD has an effective research and development pro- gram for medical biodefense countermeasures, the committee makes the following recommendation: 1. The Secretary of Defense and Congress must make the DoD pro- gram for medical biodefense countermeasures a high priority. Making the program a high priority will entail key changes: organizing the program to promote accountability and effective coordination throughout all phases of research, development, and prod- uct approval; installing leaders broadly knowledgeable in biotechnology with specific expertise in the development of vaccines and pharmaceutical products; supporting the development of a strong scientific infrastructure, including scientific personnel with expertise in pharmaceutical product development and facilities for research and animal testing; and providing the necessary funding to achieve program goals. Organizing an Effective Program with Accountability for Performance Assign Responsibility and Authority to a New DoD Agency If the development of medical countermeasures is made a genuine priority, changes will be necessary to establish a sound infrastructure for integrated and comprehensive management of the research, development,

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6 GIVING FULL MEASURE TO COUNTERMEASURES and approval processes. After reviewing various organizational options, ranging from changes within the existing organizational framework to ending the DoD-based program (see Chapter 2), the committee concluded that the task requires the creation of a new DoD agency--designated by the committee as the Medical Biodefense5 Agency--that consolidates the functions and resources of several existing activities (see Figure 2-2 for an organization chart). 2. Congress should authorize the creation of the Medical Biodefense Agency, a new DoD agency responsible for the research and development program for medical countermeasures against biological warfare agents. The committee recommends the follow- ing features for this agency: It should report directly to the Under Secretary of Defense for Acquisition, Technology, and Logistics. The functions of existing medical biodefense programs should be transferred to the new Medical Biodefense Agency, along with their personnel and funding, including the medical biodefense component of the Chemical and Biological Defense Program (in- cluding units within the Army such as the U.S. Army Medical Re- search Institute of Infectious Diseases [USAMRIID]) and related activities in the Defense Advanced Research Projects Agency (DARPA). The research and development program for medical countermeasures against infectious diseases should also be trans- ferred into the Medical Biodefense Agency. The Medical Biodefense Agency should function on the premise that to speed the development of countermeasures it is nec- essary to benefit fully from research and development efforts be- yond DoD's intramural program so as to bring the expertise and creativity of industry and the academic community to the task. The Medical Biodefense Agency should ensure that DoD's medical biodefense activities are coordinated with and take full ad- vantage of the related activities of NIH and that DoD's efforts are focused on meeting unique DoD needs. Essential functions of the new agency include the following: Establish and maintain knowledgeable leadership and effective management. 5Hereafter the term biodefense is used to describe defense against naturally occurring infectious disease as well as biowarfare agents.

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EXECUTIVE SUMMARY 7 Offer effective identification, evaluation, and prediction of, as well as advocacy for, medical biodefense needs. Encourage and facilitate coordination with related efforts of other government agencies, the academic community, and the private sector. Seek necessary resources. Promote program stability. Understand and promote the use of the best science for the task. Tailor the acquisition process for medical countermeasures to use only FDA's regulatory requirements as the basis for assessing the techni- cal merits of candidate products. Provide the means for obtaining expert advice on ethical and legal issues. The agency should have a highly qualified director with strong expe- rience in vaccine and drug research and development and manufactur- ing, including the rapidly evolving contributions of biotechnology. It is essential that the director have direct authority over the agency's budget- ing and over its full range of management and operational activities, which should extend from basic research through full-scale production. An organizational approach that creates competing lines of authority and multiple reporting relationships, as the current matrix scheme does, is not adequate to address the multiple management and scientific challenges that DoD faces. Of particular importance is ensuring that the Medical Biodefense Agency has the authority to manage the transition of candidate products from the science and technology stage into, and their progress through, the DoD acquisition system. In particular, the Medical Biodefense Agency should have the authority to use funds from science and technology ac- counts (e.g., budget activity 6.3) to support Phase 1 and even Phase 2 clinical trials before a candidate product is subject to acquisition system review. The arbitrary separation between DoD's programs to develop medi- cal countermeasures against biological warfare agents and against infec- tious diseases of military significance should be eliminated. These pro- grams address similar scientific and technological questions and require closely related expertise and facilities. Also, with concerns about biologi- cal warfare threats expanding to include a wider range of naturally occur- ring and novel biological agents, the line between the two programs is becoming even less distinct and meaningful than it was in the past. For its current scope, the DoD program to develop medical biodefense countermeasures is underfunded, based on the experience of other rel- evant government agencies and the private sector. However, the program should be better focused before any substantial increase in funding oc-

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8 GIVING FULL MEASURE TO COUNTERMEASURES curs. The Medical Biodefense Agency's budget should initially include as a baseline the funding currently allocated to the research and develop- ment activities for medical biological defense in the Chemical and Bio- logical Defense Program ($189 million for FY 2003 in budget activities 6.1 through 6.5), funding for related activities in DARPA ($79 million for FY 2003), and funding for research and product development for the infec- tious disease program ($54 million for FY 2003). Related management sup- port funding for each of these program areas (budget activity 6.6) should also be included. In addition to this baseline of $322 million, the agency should receive an initial increase of $100 million, rising over the first 5 years to $300 mil- lion above the baseline amount. This increase reflects, in part, the expecta- tion that more work will be done by civilian instead of military personnel and in non-DoD facilities, via a vibrant extramural program. The cost of salaries for military personnel and the operation of military facilities (e.g., USAMRIID) is presently covered in accounts of the military services, not the Chemical and Biological Defense Program. In addition, some candi- date products are moving into later phases of development which tradi- tionally are more costly. DoD and Congress should expect the new agency's funding needs to increase further as additional products reach this stage. This budget proposal does not include funds for the procure- ment of products after licensure. Additional funding should be provided, as well, to renovate or re- place the deteriorating and overcrowded USAMRIID facility to preserve the availability of its unique animal testing and holding space and labora- tories equipped for research involving lethal pathogens and to ensure that it has the capacity to employ up-to-date technologies in research, testing, and evaluation. The committee is strongly persuaded that creation of the Medical Biodefense Agency will be the most effective means of improving DoD's research and development program for medical biodefense countermea- sures. As a result, much of the discussion and many of the recommenda- tions throughout the report are framed in reference to this agency. The committee sees the strengths of its recommended approach as including preservation of DoD control over program priorities, integrated planning and management of all stages in the development of medical biodefense countermeasures, increased visibility of and priority for this work within DoD, increased expertise among the program leadership and managers, enhanced opportunity for coordination with related NIH work on bioterrorism countermeasures, and expanded access to contributions from extramural researchers. Disadvantages noted by the committee include the disruption of establishing a new agency and the potential difficulty of

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EXECUTIVE SUMMARY 9 attracting a director and agency staff with the necessary qualifications (see Table 2-1). In the event the Medical Biodefense Agency were not created, the need to establish a substantially more effective infrastructure for the DoD medi- cal countermeasures program, as well as the need to address other critical challenges affecting that program, will remain and should be addressed by DoD. Those efforts can and should be guided by the same consider- ations that the committee discusses as the basis for its proposals for the Medical Biodefense Agency. Establish External Oversight and Accountability for Performance An independent, external review committee, composed of experts drawn from academia, the biotechnology and pharmaceutical industries, and other segments of the private sector who bring up-to-date scientific and managerial expertise in research and product development for vac- cines and drugs, should be formed to monitor the performance of the DoD research and development program for medical biodefense countermea- sures. 3. Congress should establish an external review committee of ex- perts in the development of vaccines and drugs to review and evalu- ate the program and performance of the DoD research and develop- ment program for medical biodefense countermeasures each year. The committee should report its findings each year to the Secretary of Defense and the Congress. Maintaining DoD control over a program to develop medical biodefense countermeasures is particularly important to help ensure that unique DoD needs receive attention. However, DoD has failed to respond adequately to previous reports (e.g., IOM, 2002; Top et al., 2000) with simi- lar recommendations for change. The committee believes that the devel- opment of medical biowarfare countermeasures requires the same ur- gency as the development of medical bioterrorism countermeasures; therefore if DoD does not take steps necessary to establish an effective program and make appropriate progress within 3 years, the committee recommends, as a last resort, transferring all or part of this responsibility from DoD to an agency responsible for promoting the development of medical countermeasures for bioterrorism defense. At present, NIH ap- pears to be the best alternative because of its depth of scientific expertise and its substantial funding to support work on medical defenses against bioterrorism. However, NIH has little tradition of product development

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10 GIVING FULL MEASURE TO COUNTERMEASURES or history of focus on military-specific needs, and among many compet- ing national public health priorities this additional task may not be given sufficiently high priority. Other Challenges Requiring DoD Action For the policy and organizational changes to have the positive impact the committee seeks, the Medical Biodefense Agency also has to find ways, often in collaboration with others, to overcome other substantial obstacles to the successful development and licensure of medical countermeasures. These include: 1. establishing effective collaborations with academia and industry; 2. meeting the challenges of the regulatory process, including help- ing to establish and maintain a strong scientific base for the evaluation of biodefense products; 3. enhancing the supply and effective use of resources needed for re- search and testing of biodefense products, including laboratory animals and animal facilities and specialized laboratories; and 4. ensuring the availability of a well-trained workforce. Establishing Effective Collaborations with Academia and Industry Partnerships with the academic community and with biotechnology and pharmaceutical companies will be crucial to the success of DoD's efforts to develop medical countermeasures. Early research and discov- ery leading to new candidates for vaccine and drug countermeasures should be a mixture of intramural and extramural work, depending on the leadership's assessment of the most effective way to achieve program- matic goals. With no federally owned facilities for full-scale manufactur- ing of vaccines or drugs, industry is an essential partner. Biotechnology and pharmaceutical firms also have expertise that can aid all phases of research and development. Deterrents to participation in these efforts include complex, cumbersome contracting procedures; the potential in- stability of government funding; and concerns about potential liability risks. Larger companies have been deterred by factors including short- term opportunity costs and little commercial market for many biodefense products. To encourage increased involvement by academia and private sector firms in the development of medical countermeasures for DoD, the Medi- cal Biodefense Agency should make full use of all available funding mechanisms, including "other transactions" authority, which is specifi- cally intended for agreements with commercial firms that do not normally

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EXECUTIVE SUMMARY 11 contract with DoD. In addition, DoD has new authority to follow simpli- fied acquisition procedures and to make advance purchases of medical countermeasures that can be produced and delivered within 5 years, with the presumption, but no requirement, that those countermeasures can be licensed by FDA. DoD should make maximum use of its available author- ity to indemnify firms and others involved in developing these products. As soon as possible, Congress should extend the liability provisions in the Homeland Security Act for the smallpox vaccine to other medical biodefense countermeasures. Meeting the Challenges of the Regulatory Process As the regulatory authority reviewing data on the safety and efficacy of all medical products, FDA is another essential partner in the develop- ment of biodefense countermeasures. Interactions with FDA begin before the start of human testing of a candidate product and continue after a product is licensed and in use. The adoption of the Animal Efficacy Rule (FDA, 2002) removes a formidable barrier to licensure of medical biodefense countermeasures. Nonetheless, extensive research and testing will be needed to establish the scientific basis for applying this new regu- latory mechanism. The Medical Biodefense Agency should cooperate with FDA, NIH, and others to make data on animal models readily available. In addition, FDA should collaborate with the scientific community in ef- forts to enrich the science base that it will have to draw on in order to apply the Animal Efficacy Rule. To hasten action on medical countermeasures, FDA has adopted prac- tices that are unusually proactive. However, these expanded efforts trans- late into the need for more staff or the diversion of staff from other tasks. Although FDA has already received some additional funding and per- sonnel to support its additional work to respond to biowarfare and bioterrorism threats, Congress should ensure that funding continues to be sufficient to allow FDA to sustain these efforts. It may be possible to speed DoD's access to certain medical counter- measures through use of existing FDA authority to approve products for use by a specific population (e.g., healthy adults) or under specific cir- cumstances. Except under newly established provisions for emergency use, products still in investigational status (or not approved for a specific use) can be administered to military personnel only in accordance with informed consent procedures or with a presidential waiver of those pro- cedures. Ensuring that DoD can respond in an effective and timely man- ner to any need for emergency use of medical countermeasures will re- quire ongoing planning and coordination among various components within the department.

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12 GIVING FULL MEASURE TO COUNTERMEASURES Overcoming Current and Potential Bottlenecks Related to Research Resources Research to identify candidate countermeasures against biological warfare agents and the subsequent work necessary to bring products to licensure will require extensive use of animal models (and, thus, the fa- cilities to house animals) and specialized laboratory facilities with appro- priate biosafety features. Nonhuman primates, especially Indian-origin rhesus macaques, are in high demand for this and other types of research. In addition, clinical testing requires access to facilities that can produce small supplies of candidate countermeasures in compliance with FDA's current Good Manufacturing Practice (cGMP). The Medical Biodefense Agency should participate in a broad-based assessment of the likely demand for nonhuman primates and other labo- ratory animals, animal facilities (for testing and housing), and GMP pro- duction of candidate products necessary to support current or planned research on all types of biodefense countermeasures. The agency should promote and participate in efforts to encourage the use of nonhuman pri- mates other than Indian-origin rhesus macaques and to assess and coordi- nate the use of nonhuman primates and the use of government-owned testing facilities for biodefense research and product development. In ad- dition, the committee recommends that DoD provide funding to carry out renovations necessary to ensure that USAMRIID has fully functional biosafety level 3 and 4 (BSL-3 and BSL-4) facilities for laboratory and ani- mal research. Ensuring the Availability of a Well-Trained Workforce The nation faces a limited supply of scientific and technical personnel with the expertise needed for work on medical countermeasures (Partner- ship for Public Service, 2003). The Medical Biodefense Agency should de- fine needed workforce capabilities and aid in the development and imple- mentation of training programs designed to meet those needs. In addition, to attract and retain a skilled workforce, the agency should use DoD's newly available authority to offer salaries that are more competitive with those in academia and industry.

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EXECUTIVE SUMMARY 13 BOX ES-1 Recommendations To ensure that DoD has an effective research and development program for medical biodefense countermeasures, the committee makes the follow- ing recommendations: Making Medical Countermeasures a Priority 1. The Secretary of Defense and Congress must make the DoD program for medical biodefense countermeasures a high priority. Organizing an Effective Program with Accountability for Performance 2. Congress should authorize the creation of the Medical Biodefense Agency, a new DoD agency responsible for the research and development program for medical countermeasures against biological warfare agents. The committee recommends the following features for this agency: It should report directly to the Under Secretary of Defense for Acquisition, Technology, and Logistics. The functions of existing medical biodefense programs should be transferred to the new Medical Biodefense Agency, along with their per- sonnel and funding, including the medical biodefense component of the Chemical and Biological Defense Program (including units within the Army such as USAMRIID), and related activities in the Defense Advanced Re- search Projects Agency. The research and development program for medi- cal countermeasures against infectious diseases should also be transferred into the Medical Biodefense Agency. The Medical Biodefense Agency should function on the premise that to speed the development of countermeasures it is necessary to benefit fully from research and development efforts beyond DoD's intramural pro- gram so as to bring the expertise and creativity of industry and the aca- demic community to the task. The Medical Biodefense Agency should ensure that DoD's medi- cal biodefense activities are coordinated with and take full advantage of the related activities of NIH and that DoD's efforts are focused on meeting unique DoD needs. 3. Congress should establish an external review committee of experts in the development of vaccines and drugs to review and evaluate the program and performance of the DoD research and development program for medi- cal biodefense countermeasures each year. The committee should report its findings each year to the Secretary of Defense and the Congress. 4. If the review committee finds that after a 3-year period of operation the DoD research and development program for medical biodefense coun- termeasures has failed to make progress that the committee considers continued

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14 GIVING FULL MEASURE TO COUNTERMEASURES BOX ES-1 Continued appropriate, Congress should transfer from DoD, in part or in whole, responsibility for the development of medical biodefense countermeasures and reassign that responsibility to an agency responsible for promoting the development of medical countermeasures for bioterrorism defense, such as the NIH or another agency considered appropriate. Establishing Effective Collaboration with Academia and the Private Sector 5. The Medical Biodefense Agency should fully utilize "other transac- tions" authority as a means of encouraging academia and private sector firms to participate in the research and development of medical biodefense countermeasures to meet DoD needs. 6. Congress should authorize the Medical Biodefense Agency to sign multiyear contracts without a requirement for full, up-front funding of any termination liabilities. 7. DoD and DHHS should make maximum permissible use of statutory indemnification authority under existing legislation to encourage entities in the private sector, including universities and other research institutions and companies, to enter into agreements to develop and manufacture medical countermeasures against biowarfare agents. As soon as possible, legisla- tion should be enacted creating a system comparable to that for the small- pox vaccine under the Homeland Security Act, under which suits for personal injuries allegedly caused by biowarfare countermeasures may be brought only against the federal government, which would retain the right to recover damages resulting from such suits from manufacturers or other covered persons if their misconduct (gross negligence, illegal acts, willful misconduct, or violation of government contract obligations) was shown to be the cause of the injuries. Meeting the Challenges of the Regulatory Process 8. The Medical Biodefense Agency and NIH should cooperate in mak- ing information on animal models relevant for the development of medical biowarfare countermeasures available to qualified investigators. The DoD agency should work with NIH and engage FDA to develop additional ani- mal models that will be useful for specific agents or products of particular concern to DoD. The Medical Biodefense Agency should receive funding specifically for this task. 9. FDA should work with the scientific community to enrich the science base that the agency will have to draw on in order to apply the Animal Efficacy Rule. FDA should receive sufficient funding to support both intra- mural and extramural work on these issues.

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EXECUTIVE SUMMARY 15 10. Congress should ensure that adequate funding is provided to sup- port the additional work that FDA is carrying out in response to threats from bioterrorism and biowarfare. Overcoming Current and Potential Resource Bottlenecks 11. The Medical Biodefense Agency should participate in a national effort to support the maintenance and expansion of nonhuman primate research resources, which will be critical to the success of efforts to de- velop medical biodefense countermeasures. The Medical Biodefense Agency should be provided with sufficient funding for these activities. 12. The Medical Biodefense Agency should participate in interdepart- mental efforts to make a formal assessment of the need for facilities for animal testing and holding and for GMP-compliant manufacturing of mate- rial for clinical testing that will arise from research efforts to develop medi- cal countermeasures to biowarfare or bioterrorism agents that are under way, planned, or likely. 13. The Medical Biodefense Agency should promote the development of, and participate in a system for prioritizing the use of, specialized gov- ernment-owned testing facilities that are essential for research and devel- opment of medical biodefense countermeasures. 14. DoD should provide funding to carry out the renovations necessary to ensure that USAMRIID can continue operation of fully functional BSL-3 and BSL-4 facilities for laboratory and animal research. Ensuring the Availability of a Well-Trained Workforce 15. The Medical Biodefense Agency should define the capabilities needed for its medical countermeasures workforce, collaborate with NIAID and industry to develop a training curriculum, and support training pro- grams in areas of special expertise needed for research and development of medical countermeasures. The Medical Biodefense Agency could contrib- ute unique DoD resources in areas of aerobiology and the development of animal models of human diseases caused by biological warfare agents. 16. DoD should use its authority under the National Defense Authori- zation Act for FY 2004 (P.L. 108-136) to offer more competitive salaries to technical experts to bring necessary expertise in biotechnology and phar- maceutical research and development to the Medical Biodefense Agency. Budgeting for the Medical Biodefense Agency should reflect the need to use such provisions to recruit experienced scientific and technical per- sonnel.

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