With the recent two-animal ruling by the FDA for the licensing of drugs or vaccines directed against diseases of low or no incidence, the ferret represents an inexpensive, small, nonrodent animal model for evaluating efficacy. The ferret is attractive for pulmonary research studies because of the long trachea, large lung capacity, and bronchiolar branching. This has been particularly evident in influenza and SARS CoV research in the Southern Research Institute (www.sri.org) laboratories.
The two-animal rule states that a therapeutic may be licensed if it meets two criteria. First, the therapeutic should show adequate protection in a challenge of infection in two species of animals. Secondly, the agent must be shown to be safe in humans.
To evaluate efficacy, a comprehensive set of analyses with well-defined end points is ideal. Considerations for development and standardization of animal efficacy models include: species selection; challenge strain and dose; route of exposure, i.e., parenteral, e.g., subcutaneous; intravenous versus respiratory, i.e., intranasal, intratracheal or aerosol; clinical endpoints, i.e., mimic human disease; and challenge strain and dose effects.
At this stage it is important that standard operating protocols of the assays are qualified. Further, technical personnel are expected to qualify on the assays. One of the major challenges in conducting the efficacy studies often lies in the sheer number of animals required to obtain statistically significant data for each of these end points.
In effect, the containment of the animals in the BSL3, and the number of samples taken at each necropsy will often limit the number of animals one can employ. The transition of the efficacy model to GLP for the preclinical research stage will require the involvement of study coordination, quality assurance, and quality-control personnel. Often, these people are new to working in biocontainment and so adequate consideration needs to be made in biosafety training.
Early-phase efficacy studies are crucial for evaluation of proof of concept and immunogenicity data of candidate vaccines.
Promising vaccine candidates are further evaluated in animal models to provide additional immunogenicity data and define dose range and vaccine regimen. Animal immunogenicity data is generated with validated immunological assays and is used to bridge human immunogenicity. Together with animal efficacy data, correlates of vaccine-elicited immune protection can be identified. Finally, definitive or pivotal vaccine efficacy studies are required to be conducted under GLP to provide supporting data for licensure of vaccines.