In 2002, the United States Department of Health and Human Services Food and Drug Administration (FDA) published the final rule for New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible. The regulations, which allow the equivalent of human phase III clinical trials to be performed in animal studies when human studies are not ethical or feasible, are commonly referred to as the Animal Rule (21 CFR Parts 314 and 601, 2002).
In the introduction to the supplementary information of the Animal Rule is this statement: “All studies subject to this rule must be conducted in accordance with preexisting requirements under the good laboratory practices (21 CFR part 58) regulations and the Animal Welfare Act (7 U.S.C. 2131 et. seq.).” Because of the increased safety risk and highly infectious nature of the agents that fall under the purview of the Animal Rule, these studies are often performed in high or maximum (BSL-3 or BSL-4) biocontainment laboratories. The logistics of assuring accurate and reliable data are collected and transferred from a BSL-4 (i.e., maximum biocontainment) laboratory, conducting the study under regulatory oversight, maintaining animal records equating to clinical case files, characterizing the disease-causing agent, and designing the appropriate study to satisfy the regulatory reviewers that study data are equivalent to the outcome in humans are challenging and complex. The FDA Guidance for Industry: Product Development Under the Animal Rule provides the current thinking of expectations, including complying with the GLP regulations “to the extent practicable.”
According to the FDA Compliance Program Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies, “The Good Laboratory Practice (GLP) regulations (21 CFR part 58) were developed as a quality system for nonclinical safety studies, and thus, do not address the Animal Rule-specific studies. FDA, however, considers the GLP regulations to be a well-established and relevant framework (e.g., definitions, procedures, roles and responsibilities, and controls) for ensuring data quality and integrity in Animal Rule-specific studies.”
Use of the Animal Rule pathway to seek a regulatory decision is determined by the Agency through sponsor interaction. The FDA strongly encourages sponsors of medical countermeasures to establish early and ongoing communication with the FDA. Animal Rule studies performed at UTMB must involve the ORNcS, to include critical phase inspections performed by the Quality Assurance Unit (QAU).
The Animal Rule, associated Guidance Documents and the Compliance Program are all available on fda.gov and are listed individually under ORNcS Education and Resources.