Diagnostics and Biodosimetry
Diagnostic tests to inform the use of medical countermeasures following a Chemical, Biological, or Radiological or Nuclear (CBRN) incident is a critical response capability. Diagnostics inform the appropriate use of medical countermeasures, minimizing the quantity of said countermeasures that must be stockpiled. They also inform follow on care of casualties and they reassure concerned citizens that have not been injured during an incident. BARDA funds the development of diagnostic countermeasures for use in central laboratory facilities and at the point of care.
The diagnostics developed for CBRN threats are guided by the Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) implementation plan. BARDA advertises specific diagnostic developments of interest through the CBRN Broad Agency Announcement and specific targeted solicitations.
BARDA has funded 11 contracts for development of Biodosimetry diagnostic tools for radiation exposure threats. 6 of these 11 contractors have shown the feasibility of their proposed diagnostic and continue to receive BARDA funds and support for advanced development. While BARDA has not yet funded diagnostic developments for biological and chemical threats, future plans will address these areas once the specific needs and performance parameters for the products are better defined.
Diagnostic tests play a critical role in the early and accurate detection of infection from biothreat agents and thus are key components of the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) medical countermeasures portfolio. Guided by the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy (2012) (PDF - 543 KB), BARDA’s Biothreat Diagnostics Program is developing test systems (assays and test platforms) to respond to biothreat emergencies. Identifying through FDA-cleared rapid and accurate diagnostic tests those who are in early stages of infection with a listed biothreat agent will allow appropriate triage, patient management and allocation of medical therapeutics and resources. Strategically administering targeted therapeutics to individuals in response diagnostic test results will save lives and resources during a biothreat event.
Currently there are only limited available diagnostic test capabilities for biothreats like anthrax, and none of those are available in the clinical diagnostics market. The diagnostics being developed with support from this program are intended for use in both commercial laboratories that require rigorous test protocols and trained technicians, and in point-of-care settings enabling near-patient diagnoses at the primary care level. Point-of-care tests have the potential to improve the management of infectious diseases in resource-limited settings where laboratory infrastructure is weak or has been compromised, and access to quality and timely medical care might be a challenge. In either setting, these tests offer rapid results compared to existing test methodologies that are available today only within the CDC laboratory response network, allowing for timely initiation of appropriate therapy and/or facilitation of linkages to care and referral. Another important aspect of the test platforms under development by BARDA is their ability to be used for routine healthcare testing, making the platforms more readily available and familiar to users when needed in an emergency.
Under the Project BioShield Act (2004) (PDF - 191 KB), Pandemic and All-Hazards Preparedness Act (2006) (PDF -248 KB), BARDA was charged with developing medical countermeasures (MCMs) to address radiological and nuclear threats to the United States as determined by the Department of Homeland Security as Material Threats. In the aftermath of an improvised nuclear device (IND) detonation or a nuclear accident, having rapid and accurate measurements of internal ionizing radiation absorption in exposed persons can inform life-saving medical decisions. The biodosimetry test is a dose-dependent measurement of the biological changes caused by ionizing radiation and the body’s healing response. The test results will assist physicians in deciding the level, duration, and combination of medical care administered to an individual. BARDA’s Biodosimetry Program focuses on supporting the advanced development, verification and validation of biomarker assays and biodosimeter devices through partnerships with industry and the Public Health Emergency Medical Countermeasure Enterprise (PHEMCE). The program’s main goals are to support development and procurement of assays and devices capable of rapid measurement ionizing radiation absorbed by exposed persons allowing prioritization of limited resources.
In radiation disasters, the population is likely to encounter a number of complex exposure scenarios, including different dose ranges and rates. Therefore, triage and definitive radiation biodosimetry will require multiple tests to measure absorbed dose in patients. Qualitative point-of-care tests are designed to determine quickly whether an individual has absorbed a minimum threshold dose of radiation and needs further medical care. BARDA’s Biodosimetry Program has partnered with 11 commercial and academic test developers to develop biomarkers and assays, and to evaluate many potentially useful technological methods for use in point-of-care and high-throughput settings. Five (5) of the most promising tests using the most relevant proteomic, genomic and cytologic radiation markers remain supported by BARDA, including support to validate their utility in animal models and humans. BARDA is supporting development of two (2) point-of-care tests using different technologies with blood samples (a multiplex lateral-flow immunoassay test and a multi-array cartridge-based electrochemiluminescent test) and three (3) high-throughput laboratory-based tests that estimate the actual absorbed radiation dose received. Two (2) of the high-throughput tests under development use changes in gene expression patterns from whole blood drawn into specialized collection and stabilization blood tubes to determine the extent of radiation damage. The third high-throughput test advancing toward a product measures chromosomal damage and micronucleus generation to predict absorbed dose. In 2016, BARDA transitioned two (2) of the high-throughput devices to late-stage development and procurement under Project BioShield. BARDA anticipates additional programs to transition in 2017.
BARDA’s Biodosimetry Program will continue to work with federal and industry partners to enable the development and acquisition of radiation biodosimeter devices. A long-term goal is to have at least one point-of-care and one high-throughput laboratory-based biodosimetry test cleared by the FDA by the end of the decade and ready for procurement under Project BioShield. Ultimately, the Biodosimetry Program’s continued success will help the United States prepare for and respond effectively to a radiological incident or nuclear accident such as that at the Fukushima Daiichi nuclear power plant.