title: Animal models for Francisella tularensis and Burkholderia species: scientific and regulatory gaps toward approval of antibiotics under the FDA Animal Rule.
abstract: The development and regulatory approval of medical countermeasures (MCMs) for the treatment and prevention of bacterial threat agent infections will require the evaluation of products in animal models. To obtain regulatory approval, these models must accurately recapitulate aspects of human disease, including, but not necessarily limited to, route of exposure, time to disease onset, pathology, immune response, and mortality. This article focuses on the state of animal model development for 3 agents for which models are largely immature: Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei. An overview of available models and a description of scientific and regulatory gaps are provided.
authors.affiliation: US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, 375 E. St, SW- 12th Floor, Washington, DC 20024, USA. Email: joseph.larsen@hhs.gov.
authors.forename: M V
authors.initials: MV
authors.lastname: Stundick
authors.forename: M T
authors.initials: MT
authors.lastname: Albrecht
authors.forename: C R
authors.initials: CR
authors.lastname: Houchens
authors.forename: A Pierce
authors.initials: AP
authors.lastname: Smith
authors.forename: T M
authors.initials: TM
authors.lastname: Dreier
authors.forename: J C
authors.initials: JC
authors.lastname: Larsen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019117:Burkholderia / Q000187:drug effects*; D019121:Burkholderia Infections / Q000188:drug therapy*; D002939:Ciprofloxacin; D004195:Disease Models, Animal; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods*; D005604:Francisella tularensis / Q000187:drug effects*; D033161:Government Regulation; D064704:Levofloxacin; D014406:Tularemia / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D064704:Levofloxacin
keywords: BARDA; Burkholderia; Francisella; animal model; animal rule; antibiotic; biodefense