Description:
OBJECTIVE: The development an applicable biodosimeter in order to identify the level of radiation and/or to inform a medical treatment intervention, based on the radiation exposure. The biodosimeter must be accurate, sensitive to multiple levels of radiation, relatively non-invasive, scalable for high throughput, possess the ability to be cleared by the U.S. Food and Drug Administration (FDA), and usable in a contemporary operational environment. The dosimeter technology must diagnose quick reacting markers that allow for triage in a military operational environment within 4 hours of exposure to ionizing radiation within the boundaries of (= 1.0 Gy) with a stated statistical certainty. It is desirable that the biodosimetry device use a well qualified biomarker for absorbed radiation and the device output can be readily interpretable and obtainable. DESCRIPTION: Identify, evaluate and characterize markers of radiation injury to specific organs and tissues of physiological systems, in order to allow for timely and appropriate triage and administration of medical countermeasures and/or other medical treatments to radiation victims in a military operational environment. Ideal biomarkers are those that arise and are measurable prior to expression of tissue injury and thereby provide a time window for use of medical countermeasures that can mitigate injury. Useful biomarkers should be linked to relevant clinical outcomes such as organ failure, other major morbidity and/or mortality. It is important to develop methods to demonstrate that the change in the biomarker is related to the radiation exposure and not to other non-specific response to other health status, environmental and/or physiological factors. PHASE I: This phase will identify and justify a suitable biodosimetry tool, demonstrate feasibility, outline a plan with milestones and criteria for successful development and adaptation of the method to a validated model. The radiation biomarker(s) should be measurable in a non-invasive or minimally invasive way, allow for repeated assays over time, be sensitive to incremental changes in radiation exposure, be specific over a wide range of radiation doses and dose-rates, and be equally-reliable for different qualities of radiation (greater than or equal to 1.0 Gy). Milestones and deliverables for Phase I: 1. On completion of Phase I, the contractor will provide conceptualization, design and feasibility test results of innovative, biodosimetry tools that can function as rapid, reliable, inexpensive and easy-to-use techniques/assays and devices in the military operational environment. The biomarker signal(s) should accurately predict acute radiation injury to one or more organs and/or tissues of physiological systems within 4 hours of radiation exposure to allow for rapid triage in a military operational environment. A narrative rationale and summary of results that demonstrates a comparative evaluation, establishes suitability of the best model, and provides research findings with supplemental documentation to justify selection by providing theoretical rationale and definition of the proposed model design. 2. A project plan should be drafted regarding the optimization and development, plus evaluations of merits and feasibility of the selected concept solution. Describe any intellectual property concerns to include your company"s rights and ability to sell or license any intellectual property as well as your company"s interest in selling or licensing the intellectual property. Include any proprietary information and limitations, if any, on sharing of animal models or testing paradigms with the government and its contractors. PHASE II: Work in this phase represents the major research and development effort to culminate in a well-defined biodosimetry model. The principal deliverables of this phase will be complete documentation for concept demonstration of the model; statistically relevant test results, and a detailed proposal of the path forward to develop this biodosimetry triage tool. Focus on the development of rapid, reliable, inexpensive and easy-to-use techniques/assays and devices and imaging techniques to identify and characterize radiation injury to organs/tissues of physiological systems. Milestones and deliverables for Phase II: 1. Provide documentation for concept demonstration of in vitro and/or animal model development (i.e., small animal species, large animal species, route of exposure in relation to diagnosis). Specifically, the identification, evaluation and characterization of radiation injury biomarkers based on radiation-induced gene expression, protein expression, DNA or protein modifications, metabolomic, lipidomic, immunomodulatory, cytogenetic, inflammatory, biochemical and/or physico-chemical changes predictive of early and delayed injury to organs/tissues. 2. Provide report outlining data associated with time to diagnose, specificity and sensitivity of assays, throughput, manufacturing capabilities, and special requirements of use. 3. Summarize any efforts related to manufacturing process development, to include assay qualification and validation, production qualification and validation, and process scale-up. 4. Provide an overview of accomplishments relevant to Pre-Market Approval (PMA) or 510 (k) clearance. 5. Delivery of summary documentation with supporting data for full protocol development and final written methods as study specific procedures (SSPs) or standard operating procedures (SOPs), including material handling, facilities engineering requirements, associated SOPs such as instrument calibration dosimetry validation, and all other information to perform the work as necessary. 6. Delivery of a detailed plan for technology transfer and conversion of the model into validated method; actual work to be performed in Phase III. 7. Develop and deliver projected program with schedule and cost projections for Phase II work as defined above. 8. Executive summary report and detailed cost and schedule proposal for continuation into Phase III. PHASE III DUAL USE APPLICATIONS: Phase III will comprise the full development and validation of a biodosimetry triage tool. The system (tool, device, biomarker, or bioassay) shall be reviewed within the regulatory processes of the U.S. Food and Drug Administration"s (FDA) Center for Devices and Radiologic Health (CDRH) and, any required animal studies could have added regulatory overview under either the FDA"s Centers for Drug Evaluation and Research (CDER) or the Centers for Biologics Evaluation and Research (CBER). The phase will focus the regulatory path to a diagnostic"s FDA Pre-market Approval (PMA) or 510(k) clearance and subsequent production of a device for biodosimetry triage in a military operational environment.
