Date: April 19, 2011
Response Date: July 19, 2011
National Institute of Allergy and Infectious Diseases (NIAID)
This Notice is intended to solicit input from the radiation biology research community regarding the state of the science of animal models aimed at representing responses to radiation exposure in the human pediatric and elderly populations and that could be used to demonstrate efficacy under the Food and Drug Administration (FDA) Animal Rule. In addition, information is sought about the availability of radiation medical countermeasures (MCM) (mitigators or therapeutics) likely to be effective in treating the acute radiation syndromes (ARS) and the delayed effects of acute radiation exposure (DEARE) in these special populations. The NIH will use the information obtained in response to this RFI to develop recommendations for future research and development programs to produce effective and safe radiation medical countermeasures in these special populations.
The Department of Health and Human Services (HHS) is charged with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective MCM for Weapons of Mass Destruction. The HHS Public Health Emergency Medical Countermeasures Enterprise Implementation Plan for Chemical, Biological, Radiological and Nuclear (CBRN) Threats (HHS PHEMCE Implementation Plan) (edocket.access.gpo.gov/2007/pdf/07-1983.pdf) 1 provides a blueprint for all of its MCM-related activities, from research and development, to acquisition, storage, deployment and utilization. Among the top priorities identified by the HHS PHEMCE Implementation Plan are MCMs against radiological and nuclear threats. The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) has been charged to develop and manage a comprehensive research and early product development program focused on medical therapies and diagnostics as set by NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiation and Nuclear Threats (www.niaid.nih.gov/about/whoWeAre/Documents/radnucstrategicplan.pdf)2.
Acute Radiation Syndrome (ARS) defines a spectrum of syndromes caused by exposure to high doses of penetrating radiation in a relatively short time period. The amount and type of injuries depend on the amount of radiation and whether the exposures are whole body or partial body. Radiation exposures exceeding 2 Gy in adults can result in the depletion of hematopoietic stem cells and cellular progenitors in the bone marrow, which may lead to severe neutropenia, thrombocytopenia and death. Higher radiation doses can cause gastrointestinal (GI) complications, including mucosal barrier breakdown, bacterial translocation, and loss of GI structural integrity, which can lead to rapid death. Victims who survive the ARS may suffer from DEARE, which include pulmonary, renal and cutaneous complications occurring weeks to months after radiation exposure. The development of animal models of ARS and DEARE is necessary to demonstrate efficacy and support licensure by the FDA of MCMs, which then can be procured and stored in the Strategic National Stockpile (SNS). While there has been progress in the development of radiation exposure models representing human adults, questions remain whether they are adequate to represent or predict the radiation responses in infants, children, and the elderly which, together, correspond to 37% of the general population. These special populations may exhibit radiation sensitivities that differ from adults and/or display additional complications. Developing human surrogate pediatric and geriatric animal models as well as establishing biomarkers for radiation exposure and identifying safe and effective medical countermeasures will be instrumental to addressing this issue. To establish the state of the science and facilitate research on MCMs targeted at pediatric and elderly populations, the NIAID is looking for information on:
1. Parker, Gerald, DVM. HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for Chemical, Biological, Radiological and Nuclear Threats. Federal Register / Vol. 72, No. 77 April 23, 2007.
2. National Institute of Allergy and Infectious Diseases, U.S. Department of Health and Human Services. NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats. 2005.
Request for Information
NIAID is soliciting input from the radiation biology research community regarding animal models aimed at representing pediatric and geriatric responses to radiation exposure, and radiation MCM likely to be effective in mitigating and/or treating ARS and DEARE. Areas of research and development that are of interest include, but are not limited to, the following:
Development of small (e.g., rodent) and large (e.g., dog, non-human primate, etc.) animal models that reflect the radiotoxicity observed in the young and elderly and are predictive of the responses of these human populations to mitigation by MCMs.
Development of MCMs (including small molecule, biologics and/or cell therapies) to mitigate/treat medical consequences of radiation exposure in pediatric and geriatric populations, including approaches to treat hematopoietic and GI-ARS, as well as DEARE complications. Recognizing that one model may not be sufficient for all of the medical effects of radiation exposure, development of models for hematopoietic and GI-ARS, as well as animal models for DEARE are of interest. Within pediatric model development, separation of models developed to represent infants (<2 years) and juveniles (2 years to 18 years) may be appropriate. Information on the development of in utero radiation exposure models is not requested within this RFI and should not be submitted.
Discovery/establishment of biomarkers for radiation injury in pediatric and/or elderly individuals, including total-body or organ-specific markers of exposure.
Formulation development for candidate MCMs that permit ease of administration in the special population and in a mass casualty incident.
Studies that characterize the natural pathophysiology of radiation exposures in these special populations and identify additional pathologies, injuries or delayed effects.
Studies that investigate the differences in drug pharmacokinetics and pharmacodynamics between irradiated and unirradiated pediatric and/or elderly populations.
Studies that demonstrate safety of candidate MCMs in special populations and/or surrogate animal models. Studies in animal models should be detailed to demonstrate efficacy of the proposed products to minimize damage and restore normal function. Clinical studies using human tissue samples or data from irradiated patients may be provided if the results are likely to be relevant to the treatment of humans exposed to terrorist, accidental radiological, or nuclear attack.
Information on mutagenesis and/or carcinogenesis arising from exposure of pediatric and/or elderly populations is not requested in this RFI and should not be submitted.
This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any identified opportunities. Please note that the Government will not pay for response preparation or the use of any information contained therein. Responses to this RFI are voluntary. Acknowledgement of receipt of responses will not be made. No basis for claims against the NIAID shall arise as a result of a response to this request for information or the NIAID’s use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). As previously indicated, the NIAID may use the information gathered to develop grant, contract, or other funding initiatives. Any proprietary information should be so marked.
Information must be submitted by July, 19, 2011. Responses should be limited to 10 pages and marked with this RFI identifier (NOT-AI-11-044). Responses are preferred in electronic format and can be e-mailed to the attention of:
Dr. Francesca Macchiarini
Program Officer, DAIT, NIAID, NIH, DHHS
6610 Rockledge Drive, Room 5302
Bethesda, MD 20892-7612
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