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 licensure 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 licensure 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; and

Evidence of capability to conduct studies in two animal models, with at least one being a large animal model. Subcontracting is an available option to expand capabilities.

The Pandemic and All Hazards Preparedness Act (PAHPA) of 2006 established the Biomedical Advanced Research and Development Authority (BARDA) to support development and acquisition of medical countermeasures (MCMs) to prevent or treat the medical consequences of chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza (PI), and emerging infectious diseases (EID). These MCMs include vaccines, therapeutics, diagnostics, and medical devices. Additionally, BARDA is entrusted to foster innovation of technologies that enable better manufacturing, testing, and utilization of these medical countermeasures.

The development of animal models is a key element in the successful development of MCMs for RadNuc threats, particularly since efficacy of products directed against most of these threats cannot be verified using clinical studies. In 2002 and 2015, the FDA amended its regulations for drugs and biologics to permit approval or licensure of MCMs 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. 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 necessary for drug approval or licensure is based solely on efficacy data derived in animals. Demonstration of the safety of the medical countermeasure (drug or biologic) is done in normal, healthy adult humans and in some cases safety in a related pathology particularly if the drug or biologic is already approved for the related pathology.