Recent advances in medical countermeasure development against acute radiation exposure based on the U.S. FDA animal rule.

Recent advances in medical countermeasures has been dependent on the Food and Drug Administration Animal Rule and the guidance document provided for industry on product development under the animal rule. The criteria outlined therein establish the path for approval under the animal rule. The guidance document, along with the funding and requirements from the federal agencies provided the basic considerations for animal model development in assessing radiation effects and efficacy against the potential lethal effects of acute radiation-induced acute radiation syndrome (ARS) and the delayed effects of acute exposure (DEARE). Animal models, essential for determining medical countermeasure (MCM) efficacy, were developed and validated to assess organ-specific, potentially lethal, radiation effects against the gastrointestinal (GI) and hematopoietic ARS and radiation-induced delayed effects to lung and associated comorbidities of prolonged immune suppression, gastrointestinal injury and damage to the kidney and heart. Partial-body irradiation models where marginal bone marrow was spared resulted in the ability to evaluate the concurrent evolution of multiple organ injury in the ARS and the delayed effects of acute exposure in survivors of acute radiation exposure. There are no MCM for prophylaxis against the major sequelae of the ARS or DEARE. Neither are there MCM that will mitigate the GI-ARS or DEARE consequent to potentially lethal exposure from a terrorist event or major radiation accident. The gap in MCM for prophylaxis may extend to mixed neutron/gamma radiation if current modeling predicts prompt exposure from an improvised nuclear device. Recent advances in MCM development have accrued due to federal and corporate funding, clarification of the critical criteria for efficacy within the Food and Drug Administration Animal Rule and the concomitant development and validation of additional animal models. These models provided for a strategic and tactical approach to determine radiation effects and MCM efficacy.