BARDA Radiological and Nuclear (RADNUC) Animal Model and Medical Countermeasures (MCM) Development

The Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), seeks appropriate Good Laboratory Practices (GLP) facilities that are adequate and available to establish new or use existing animal models for the development of radiological and nuclear MCMs. In these models, the radiation exposure should be comparable to that which produces the human disease or condition and the pathophysiological mechanism of its toxicity should be reasonably well-understood and mimic the human disease/condition as closely as possible. These models will be used to test the efficacy of potential RadNuc MCMs. The mechanism of action of the countermeasure will also need to establish the utility of the animal model as a surrogate for humans. Laboratories must meet the following mandatory eligibility criteria to be considered: Evidence of Federal, State, and/or local licenses as required for the operation and control of a clinical level irradiation facility with qualified personnel for the operation, assigned safety restrictions, domestic and instrument calibration per licensed Health Physics authority. Evidence of Federal, State, and/or local licenses as required for the storage, use, and disposal of select agents such as chemical agents and radionuclides and training of all associated staff responsible for the use of such material. Evidence of accreditation or licensure of the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) accreditation or equivalent. Evidence of U.S. Department of Agriculture (USDA) animal research facility license, or equivalent. Completion of at least one good laboratory practice (GLP) study. Evidence of capability to conduct either small or large (or both) animal model studies. Provided plan for conducting studies in two animal models, with at least one being a large animal model. Subcontracting is an available option to expand capabilities. HHS, through the interagency Public Health Emergency and Medical Countermeasure Enterprise (PHEMCE) is responsible for the integration of requirements for the advanced development and procurement of MCMs for CBRN threats specified by the Department of Homeland Security as material threats. The HHS PHEMCE Strategy for Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Strategy), published in the Federal Register on March 20, 2007 describes the strategic policy goals and objectives for identifying requirements and establishes the priorities for the development of the MCMs. The HHS PHEMCE Implementation Plan for Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Implementation Plan), published in the Federal Register on April 2007 with subsequent updates between December 2012 and 2017, delineates HHS MCM priorities for research, development and acquisition to address the highest priority CBRN threats. The development of animal models is a key element in the development of MCM for CBRN threats, particularly since efficacy of products against most of these threats cannot be verified using human clinical studies. In 2002 and 2015, the FDA amended its regulations for drugs and biologics to permit approval or licensure of medical countermeasures based on substantial evidence of effectiveness in animals when adequate and well-controlled efficacy studies in humans cannot be conducted because it would be unethical to expose healthy human volunteers to lethal or disabling toxic CBRN substances, and relevant field efficacy trials in humans are not feasible. This change in the regulations (21 CFR 314.600 for drugs and 21 CFR 601.90 for biologics), commonly referred to as the Animal Rule, made the design and conduct of adequate efficacy studies in appropriate animal models of paramount regulatory importance, since the inference of efficacy in humans is based on efficacy data derived in animals. The primary demonstration of safety of the MCM (drug or biologic) is conducted in human clinical studies, although non-clinical data will also be used to evaluate safety.