of aerosolized exposure in animals to guide development and characterization of new animal models. There are many methodological challenges in generating reproducible exposures, e.g. generation of viable aerosols, consistent exposure of animals, appropriate quantification of dose, and comparison of results among laboratories. Also, the use of animal models to demonstrate efficacy during the drug approval process is a relatively new approach for the regulatory community and there are issues that still need to be addressed.
The NIAID approached the National Research Council with a request that it prepare a short consensus report that articulates the difficulties of testing countermeasures to aerosolized bioterrorism agents in animals and identifies opportunities that can be pursued to improve current testing efforts. As part of this project, NIAID requested that a workshop be organized to bring together select agent researchers, including researchers from NIAID and U.S. Army Medical Research Institute of Infectious Diseases, as well as leaders in complementary areas of science, particularly inhalation toxicologists, microbiologists, aerosol scientists, and statisticians. This report is based on the presentations and discussions held at this workshop on July 6 and 7, 2005, as well as further research and deliberations by the authoring committee following this workshop.
The committee approached its task by considering how to improve and standardize studies that generate efficacy data in animals. The committee generally focused on technical issues regarding the generation of consistent and reproducible exposures, which are key to producing scientifically-sound efficacy data, but also touched on issues to be considered in selecting an animal model. Studies to establish human dose response to a bioterrorism agent or conduct a risk assessment for a bioterrorism event are beyond the scope of the committee’s charge.
The committee organized its efforts and report by focusing on four parts of the experimental design process: the selection of the animal model to be utilized, the generation and characterization of the aerosolized bioterrorism agent, characterization of dose, and selection and delivery of dose. For each part of the experimental design, the committee identified issues that potentially affect the quality and reproducibility of data, and then identified experimental approaches and technology that might overcome those challenges. The committee also took a holistic approach to their overarching task, and identified workforce, infrastructure, and regulatory issues that could present challenges to testing countermeasures to bioterrorism agents.
The following recommendations have been developed to address the major challenges identified by the Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents.