Giving Full Measure to Countermeasures Addressing Problems in the DoD Program to Develop Medical Countermeasures Against Biological Warfare Agents (2004) / Chapter Skim
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3 Challenges in the Research and Development of Medical Countermeasures Against Biological Warfare Agents
3 Challenges in the Research and Development of Medical Countermeasures Against Biological Warfare Agents
Pages 73-102
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In addition, accelerating the development and testing of countermeasures will require ensuring the availability of adequate supplies of nonhuman primates and other laboratory animals, specialized laboratory facilities with appropriate biosafety features, and facilities in which test lots 73
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. In this chapter, the committee reviews these challenges and recommends steps that DoD, acting principally through the proposed Medical Biodefense Agency, should take on its own or in collaboration with others.
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The committee makes recommendations regarding some of these options below. Full Use of Existing Grant and Contract Mechanisms The committee expects the proposed Medical Biodefense Agency to make full use of all means at its disposal to ensure that the most suitable organization conducts the work needed to achieve program goals.
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development projects under which dual-use technology research or development is carried out sharing the costs between DoD and nongovernmental entities · Other Transactions: mechanisms other than a contract, grant, or cooperative agreement used with commercial firms that do not normally contract with DoD. They generally do not require compliance with federal laws and regulations that apply to procurement contracts, grants, and/or cooperative agreements.
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5. The Medical Biodefense Agency should fully utilize "other trans actions" authority as a means of encouraging academia and private sector firms to participate in the research and development of medi cal biodefense countermeasures to meet DoD needs.
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The appropriations bill for the Department of Homeland Security (DHS) 2 makes $5,593 million available until September 30, 2013, for securing biodefense countermeasures.
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As of December 2003, neither the Senate nor the House had acted on this bill. Liability Considerations Most medical biodefense countermeasures are likely to receive FDA approval under the Animal Efficacy Rule and, thus, without direct evidence of efficacy in humans.
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Concerns about liability may extend as well to university researchers and other not-for-profit research organizations. Having heard from biotechnology and pharmaceutical industry representatives and from a consumer advocate, the committee is persuaded that it is important for the government to address industry concerns about product liability risks as part of efforts to accelerate the development of medical biodefense countermeasures.
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As soon as possible, legislation should be en acted creating a system comparable to that for the smallpox vaccine under the Homeland Security Act, under which suits for personal injuries allegedly caused by biowarfare countermeasures may be
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It will be necessary to establish the biologic plausibility of the equivalence of animal and human responses to the disease agents and to the countermeasures in question. DoD-sponsored investigators have helped develop some of the few existing animal models of human disease caused by biological warfare agents or of protection against those dis 5Federal Food Drug and Cosmetic Act Section 505i; The Public Health Service Act, Regulation of Biological Products, Section 351 Subpart 1.
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has identified a need for additional work to develop animal models for almost all of the biological agents considered to pose the most serious threat for bioterrorism (referred to as "Category A" agents) .6 Although the committee believes that NIAID should be the primary sponsor of such work, the Medical Biodefense Agency should ensure that information on animal models developed by DoD investigators is available to researchers and the product development community, including FDA.
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. It permits marketing approval on the basis of clinical trials using surrogate endpoints reasonably likely to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity, often in conjunction with requirements for postmarketing studies.
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In discussions with the committee during its information-gathering meetings, both DoD and industry representatives noted the agency's proactive practices related to biodefense countermeasures.7 FDA's expanded efforts require additional staff time, which translates into the need for more staff or the diversion of staff from other tasks. The committee understands that FDA is giving biowarfare or bioterrorism countermeasures de facto priority status.
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With pyridostigmine bromide, for example, the recently approved labeling indicates that its use as a pretreatment against nerve agent exposure is "for military combat medical use only" (FDA, 2003c)
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The IND provisions are useful for protecting research subjects, but are not ideal for administering a vaccine or drug to a large military contingent to provide force health protection, particularly because of the requirement to obtain and document informed consent. The issue is especially challenging because, at the time of the Gulf War of 19901991, DoD requested and was ultimately granted a waiver of the informed consent requirements for the use of two investigational products, pyridostigmine bromide and botulinum toxoid vaccine, on the grounds that informed consent was not feasible for military exigencies (FDA, 1990; Rettig, 1999)
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With the passage of the National Defense Authorization Act for Fiscal Year 2004 (P.L.
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These resource needs span the process from discovery to licensure. Of particular importance for the development of medical biodefense countermeasures is the availability of nonhuman primates to serve as test subjects, specialized laboratory and animal testing facilities, and facilities for producing candidate countermeasures in compliance with cGMP standards.
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The committee further emphasizes the need for coordination in the particular resource areas discussed below. Resources for Product Research and Development Availability of Nonhuman Primates Studies using nonhuman primates are likely to be important in meeting the requirements of the new Animal Efficacy Rule because of the ani
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It is important that the Medical Biodefense Agency, NIH, and others involved in biodefense research participate in and provide financial support for coordinated efforts to increase domestic cage and breeding capacity as part of efforts to expand the supply of nonhuman primates. With the growth of medical biodefense research, it is imperative for the Medical Biodefense Agency, NIH, and others involved in this work to assess their current and future needs for nonhuman primates and to coordinate their use of the available animals.
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Furthermore, the military threat posed by most biological agents is generally considered to be from aerosol exposure. As a result, efficacy testing for candidate countermeasures for DoD requires facilities in which test animals can be subjected to aerosol challenge under high-level biocontainment conditions.
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In view of the targeted market for medical countermeasures against biowarfare agents, industry may have limited incentives to make cGMP facilities available to manufacture the small amounts of material needed for early clinical testing. Increased access to facilities designed to produce materials for at least Phase 1 and 2 clinical trials would aid the development of candidate vaccines and drugs.
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12. The Medical Biodefense Agency should participate in interde partmental efforts to make a formal assessment of the need for fa cilities for animal testing and holding and for GMP-compliant manufacturing of material for clinical testing that will arise from research efforts to develop medical countermeasures to biowarfare or bioterrorism agents that are under way, planned, or likely.
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The committee notes in particular the need for people with expertise in aerobiology, in the development of animal models of human disease caused by biological warfare agents, and in the advanced development and manufacture of medical products, particularly vaccines. There is also a shortage of veterinarians with the necessary expertise in laboratory animal medicine, management, and pathology, including those with special training in the care and use of nonhuman primates (NRC, 2004)
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The Medical Biodefense Agency could contribute unique DoD resources in ar eas of aerobiology and the development of animal models of hu man diseases caused by biological warfare agents.
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Budgeting for the Medical Biodefense Agency should reflect the need to use such provisions to recruit experienced scientific and technical personnel. REFERENCES Albert V
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Pre sentation to the Institute of Medicine and National Research Council Committee on Accelerating the Research, Development, and Acquisition of Medical Countermeasures Against Biological Warfare Agents, Meeting II. Washington, DC.
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Presentation to the Insti tute of Medicine and National Research Council Committee on Accelerating the Re search, Development, and Acquisition of Medical Countermeasures Against Biological Warfare Agents, March 19. Fort Detrick, MD.
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Presentation to the Institute of Medicine and National Research Council Com mittee on Accelerating the Research, Development, and Acquisition of Medical Coun termeasures Against Biological Warfare Agents, Meeting V Washington, DC.
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2001. Report on Biological Warfare Defense Vaccine Research and Development Programs.
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