TABLE 2.

Open Discussion Key Points

Licensure challenges associated with the development of pro-platelet therapies for use after radiation exposure (e.g., species specificity of some approaches, use of animal and/or human-derived cells for cell therapy approaches) exist. Potential means to address these challenges include using novel animal models and/or homologous animal cell preparations as the surrogate human product in an animal model.

The FDA Animal Rule is interpreted to mean that a candidate MCM using this licensure pathway should (generally) have efficacy data in at least two animal models (at least one non-rodent) that are predictive for humans. These pivotal efficacy studies must be performed in compliance with GLP and have clinically relevant end points (usually mortality or major morbidity) and MoA of the therapy across species will need to be assessed. Ample PK/PD data should be available to allow for the selection of an appropriate human dose.

Animal model development is critical, given the Animal Rule guidance. Species that are selected for study should respond both to radiation and to the candidate MCM in a way that is similar to or predictive of the human response.

Supportive care of the animals should also parallel the level of medical management that would be expected for humans. Testing of the MCM in the presence of another treatment that might be considered standard of care for a radiation accident victim could also provide important data.

Radiation exposures, to the extent that it is possible to do so, should mimic the anticipated real-world exposure scenarios, including the type of radiation, dose and dose rate. The need to conduct studies in partially shielded animal models should be discussed and agreed upon with FDA.

In addition, the dose modification factor (DMF) for the approach should be determined, so as to allow efficacy comparisons between candidate therapeutics.

Regulatory strategies should be established early in the development of a drug for a radiation counterterrorism indication. Discussion with FDA review divisions in CDER or CBER should be initiated once proof-of-concept data are obtained by the Sponsor.

Research gaps still exist, especially in the area of MCM development for special populations, such as children, the elderly and immunocompromised individuals. Working together, the different components of the U.S. Government must continue to provide guidance and funding to researchers developing pipeline and advanced MCMs for radiation indications.