Antimicrobial Dose Selection under the Animal Rule

The Food and Drug Administration's (FDA's) Animal Rule provides a unique regulatory pathway for drugs and biologics intended to treat serious or life-threatening conditions caused by exposure to lethal or permanently disabling chemical, biological, radiological, or nuclear agents when human efficacy studies are not ethical and field trials are not feasible. Human dose selection under the Animal Rule is based on integrating the totality of clinical pharmacology evidence collected in in vitro, animal, and human studies. This review discusses the necessary pharmacokinetic and pharmacodynamic information and methods for determining the effective human dose of antimicrobials under the Animal Rule and presents case studies illustrating the utility of a totality of evidence approach for different methods.

Automated summary

The Animal Rule provides a unique regulatory pathway for drugs intended to treat serious conditions caused by exposure to lethal agents when human efficacy studies are not ethical. Human dose selection under the Animal Rule is based on integrating clinical pharmacology evidence from in vitro, animal, and human studies.