Clinical and Translational Pharmacology Considerations for Anti-infectives Approved Under the FDA Animal Rule.

Abstract

The US Food and Drug Administration's Animal Rule provides a pathway for approval of drugs and biologics aimed to treat serious or life-threatening conditions wherein traditional clinical trials are either not ethical or feasible. In such a scenario, determination of safety and efficacy are based on integration of data on drug disposition and drug action collected from in vitro models, infected animals, and healthy volunteer human studies. The demonstration of clinical efficacy and safety in humans based on robust, well-controlled animal studies is filled with challenges. This review elaborates on the challenges in the translation of data from in vitro and animal models to human dosing for antimicrobials. In this context, it discusses precedents of drugs approved under the Animal Rule, along with the approaches and guidance undertaken by sponsors.