The purpose of this Funding Opportunity Announcement (FOA) is to encourage Small Business Innovation Research (SBIR) grant applications (Phase I [R43] and Phase II [R44]) focused on specific product development activities for radiological/nuclear medical countermeasures leading to Investigational New Drug (IND) or Investigational Device Exemption (IDE) submission packages to the U.S. Food and Drug Administration (FDA). This FOA will support non-clinical and preclinical product development activities to advance new medical countermeasures in preparation for, Phase I clinical trial safety studies, "Good Laboratory Practices" (GLP) animal model pivotal efficacy studies, and FDA licensure. In support of the overall program goal for the rapid development of safe and effective radiological/nuclear medical countermeasures for clinical use under emergency situations, the National Institute of Allergy and Infectious Diseases (NIAID) encourages the development of products that: 1) mitigate and/or treat the acute radiation syndromes (ARS) and/or the delayed effects of radiation exposures; 2) eliminate internal radionuclide contamination (decorporation); or 3) accurately determine individual radiation exposure levels (biodosimetry).
Very few medical products have been shown to counter the acute and long-term injuries that can result from a nuclear or radiological accident or attack. Following the September 11, 2001 attacks, national and global attention regarding the threat of nuclear attacks and concern over illicit trafficking of radioactive materials has increased. Recent non-terrorist related accidents have also increased global and national attention to the need for medical countermeasures, decorporation agents and biodosimetry devices. The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was given the responsibility by the Department of Health and Human Services (DHHS) to identify, characterize and develop new medical countermeasure products against radiological and nuclear incidents that may cause a public health emergency.
In 2005, the NIH published a Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats http://www.niaid.nih.gov/about/whoWeAre/Documents/radnucstrategicplan.pdf This agenda includes focused product development of medical countermeasures, ARS mitigators or treatments, radionuclide decorporation agents, and biodosimetry techniques and devices to fill an important Public Health product need and for inclusion in the Strategic National Stockpile (SNS). In 2012, NIAID updated the strategic plan and research agenda in the Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats Progress Report: 2005–2011 and Future Research Directions: 2012–2016 http://www.niaid.nih.gov/topics/radnuc/Documents/radnucprogressreport.pdf NIAID has established several contract and grant programs to initiate research and product development efforts: http://www.niaid.nih.gov/topics/radnuc/Pages/default.aspx. This funding opportunity will provide additional support for development of promising candidate medical countermeasures and devices.
This FOA will support activities leading to the development, preparation and submission of an IND or an IDE for eventual FDA licensure. It is anticipated that in most cases, licensure or approval of proposed medical countermeasures will occur in accordance with the FDA Animal Rule (see 21 CFR 314.600 Subpart I for drug products and 21 CFR 601.90 Subpart H for biologic products http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM399217.pdf). Thus, studies in animal models will be required to demonstrate efficacy of the medical countermeasure products. Under the FDA Animal Rule, GLP animal model pivotal efficacy studies serve as surrogates for Phase III clinical efficacy studies. This FOA, however, will NOT support Phase I clinical trials or GLP pivotal efficacy studies. Animal studies leading to GLP pivotal studies, including preclinical efficacy studies and GLP-pilot studies, will be supported by this FOA.
The spectrum of development activities supported by this FOA includes proof of concept studies; preclinical efficacy work; statistically valid developmental efficacy studies; GLP-pilot studies to inform the design of GLP pivotal efficacy study protocols; non-clinical determination of safety, toxicology and metabolism; formulation development as well as determination of dose and dose scheduling; cGMP manufacturing scale-up and drug product stability studies; development of GLP analytical methods for efficacy studies; product characterization; and completion of IND or IDE packages for FDA submission.
The priority areas of product development from proof of principle to submission of an IND/IDE package include, but are not limited to, the following examples:
- Medical products and regimens that mitigate and/or treat radiation injury post-exposure (i.e., administration of first dose to start at least 24 hours after radiation exposure), with emphasis on broad activity (i.e. multi-syndrome and/or multi-tissue), ease of administration in a mass casualty and emergency scenario; safety; and long shelf-life;
- Medical products and regimens that accelerate the removal of inhaled, insoluble particles containing radionuclides from the lungs. Radionuclide decorporation agents that facilitate elimination of a range of radionuclides from the body or blocking agents that prevent the absorption of radionuclides in the body;
- Minimally invasive or non-invasive biodosimetry devices useful for emergency triage that can rapidly and accurately distinguish individuals who need treatment from those who do not, and that can identify and measure internal and external exposure; and
- New medical product formulations that can be easily administered to civilian populations, including special populations (e.g. infants, children, elderly, and the immunocompromised) in emergency situations.
Guidance for the approval of decorporation agents to treat internal radionuclide contamination has been provided by the FDA and is available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071944.pdf.