Notice Number: NOT-AI-13-057
Release Date: July 25, 2013
Response Date: August 19, 2013
National Institute of Allergy and Infectious Diseases (NIAID)
This is a Request for Information (RFI). This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this RFI is to obtain knowledge and information for project planning purposes.
This Notice is intended to solicit input from the radiation biology research and product development communities about existing animal models that represent the human response to radiation exposure and the product development capabilities that could be used to develop medical countermeasures (MCMs) for Food and Drug Administration (FDA) licensure under the Animal Rule. The NIH will use the information obtained in response to this RFI to design future programs to develop effective and safe radiation medical countermeasures.
The Department of Health and Human Services (HHS) is charged with protecting civilian populations by providing leadership in research, development, acquisition, deployment, and use of effective MCMs for weapons of mass destruction. The HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for Chemical, Biological, Radiological and Nuclear (CBRN) Threats (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2012-PHEMCE-Strategy) 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. NIAID, on behalf of the National Institutes of Health (NIH) has been charged to develop and manage a comprehensive research and development program focused on medical therapies and diagnostics as outlined in the NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiation and Nuclear Threats (http://www.niaid.nih.gov/about/whoWeAre/Documents/radnucstrategicplan.pdf and http://www.niaid.nih.gov/topics/radnuc/Documents/radnucprogressreport.pdf).
Acute radiation syndrome (ARS) encompasses a spectrum of pathophysiologic changes caused by exposure to high doses of penetrating radiation in a relatively short time period. Injuries sustained depend on the dose and extent of radiation exposure (e.g., whole- 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 from infection or hemorrhage. 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. Individuals who survive ARS may suffer from the delayed effects of acute radiation exposure (DEARE), which can include pulmonary, renal and cutaneous complications occurring weeks to months after radiation exposure.
The NIH is committed to addressing the need for radiation/nuclear MCMs that are suitable for a mass casualty situation and to support research and development efforts to make them available for advanced development and procurement by the Biomedical Advanced Research and Development Authority (BARDA) and the Strategic National Stockpile (SNS). These efforts include developing suitable animal models for radiation injury, evaluating the safety and efficacy of promising MCMs in these models, and providing other product development-related services. For the purposes of this RFI, the terms “MCM(s)” and “drug(s)” will include drugs, biologics and cellular therapies.
Information received will inform NIAID program on the existing capabilities and capacities, depending on contract type and program needs, and that would span a five-year period, beginning in 2015. Interested organizations are encouraged to provide a white paper that includes organizational experience and staff expertise in the following areas:
Organization: Describe in general the structure of the organization and its administrative capabilities and experience. Include data and document management systems, good laboratory practice (GLP) capabilities (21 CFR 58), radiation dosimetry, and coordination of multiple areas of interest.
Radiation injuries: Describe capabilities and experience using animal models for the radiation syndromes listed below. Include radiation source(s), species and/or strains used, radiation dose-response relationships, assessment of mortality or major morbidity, any available supportive care, and tools that are available to discern the mechanisms of radiation injury and possible recovery.
Radionuclide modeling and decorporation: Describe capabilities and experience using animal models of radionuclide contamination. Include radionuclides that can be used, species and/or strains, route of radionuclide administration, assessment of radionuclide body burden and excretion, and experience with radionuclide decorporation studies.
Animal safety/pharmacology: Describe capabilities and experience with safety/toxicity and pharmacology testing in animals to support clinical use of a therapeutic product. Such testing shall also include all tests required for an IND application. Studies may be performed in accordance with GLP regulations. Examples include the development of validated analytical methods for assessing concentrations of test article or active metabolite in biological fluids, such as blood, for testing of pharmacokinetics (PK), validated methods for testing pharmacodynamics (PD), and other parameters, preclinical acute and chronic toxicity, PK/toxicokinetic parameters, bioavailability studies, absorption, distribution, and metabolism and excretion (ADME) studies.
Phase I clinical: Describe capabilities and experience with conducting Phase I clinical safety/PK studies in normal human subjects to support approval of a radiological/nuclear medical countermeasure candidate drug. This requirement could also include studies that help to define mechanism of action and guide the dosing of a MCM (PK and/or PD).
Chemistry, manufacturing and control (CMC) support services: Describe capabilities and experience manufacturing drug candidates to support clinical use, including formulation development, production development, stability testing and current good manufacturing practice (cGMP) manufacture of drug candidates.
This Notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this Notice should ensure that its response is complete and sufficiently detailed. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.
Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities in accordance with the FAR Part 5. However, responses to this Notice will not be considered adequate responses to a solicitation.
Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
Information must be submitted by August 19, 2013. Responses should follow this format: 3 pages organization description and 2 pages per area of interest or bulleted item under “Radiation injuries” (radiation syndrome/species combination). A list of relevant scientific references or URLs may be provided separately. Include respondents’ technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and email addresses. Mark the responses with the RFI identifier (NOT-AI-13-057) and email as an attachment (Microsoft Word or PDF) to the attention of the Program Contact listed below.
Please direct all inquiries to the NIAID Program contact:
Dr. David R. Cassatt
National Institute of Allergy and Infectious Diseases (NIAID)