BARDA Chemical Animal Model Development

The Biomedical Advanced Research and Development Authority (BARDA) within the Oice of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), seeks laboratories capable of controlled exposures of various animal species to chemical agents, and capable of establishing models to evaluate the efficacy of potential MCMs. Task Orders derived from this IDIQ contract will be assigned to one of two groups: Group A covers pulmonary agents, cyanide, opioids, toxic industrial chemicals (TICs), and other potential chemical agents of concern by inhalation, ingestion, and topical routes. Performers in this group must have performed at least one GLP study in the past three (3) years. Group B covers nerve agents and vesicants (including sulfur mustard) by inhalation, ingestion, and topical routes. Performers in this group must be capable of working with chemical threat agents (i.e. OPCW Schedule 1 compounds). Please note that laboratories must be capable of performing tasks from at least one of the above groups (i.e., meeting the capabilities/requirements to belong to one group would suffice) Laboratories may belong to of either group so long as they meet the requirements for that group. In these models, the challenge dose should typically be similar 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. When these models are used to test the efficacy of potential MCMs for chemical threat agents, the mechanism of action of the countermeasure in the animals will need to match the expected mechanism of action in human victims. 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 chemical, threats, particularly since efficacy of products directed against most of these threats cannot be verified using clinical studies. In 2002, 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.