FDA Animal Rule: Overview & Impact on Drug Development

July 9, 2024

What is the Animal Rule?

The Animal Rule, a regulation set by the US Food and Drug Administration (FDA), applies to the development and testing of drugs and biological products intended to reduce or prevent serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic agents such as chemical, biological, radiological, or nuclear substances, where human clinical trials are not possible or ethical.

Under the Animal Rule, efficacy is established based on adequate and well-controlled animal models of the human disease or condition of interest. Under the rule, Sponsors developing new drugs and biological products, must still demonstrate the product’s safety in humans. Products can be approved under the rule when the following conditions are met:

  • There is a reasonably well-understood physiological response to the toxicity of the substance and its prevention or measurable reduction by use of the product:
  • The effect is demonstrated in more than one animal species and can be used to predict the response in humans unless the effect can be demonstrated in a single animal species sufficiently well to be used to predict the response in humans
  • The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity
  • The data or information on the kinetics and pharmacodynamics of the product in animals or humans allows for selection of an effective dose in humans

How Does FDA's Animal Rule Impact Drug Development?

The Animal Rule has a significant impact on drug development, particularly for drugs and biological products intended to reduce or prevent serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic agents.

Key impacts of FDA’s Animal Rule include:

Efficiency: Products developed under the Animal Rule may be eligible for two of the expedited development and review programs (fast track and priority review) or other FDA programs such as orphan drug designation. The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act of 2003 (PREA) may also apply to drugs developed under the Animal Rule. Through these expediated pathways, products have the potential to be available to the public earlier and use fewer resources when compared to approval through the traditional regulatory pathway.

Regulatory Considerations: The Animal Rule introduces specific regulatory considerations for drug development. These include a development plan, access to investigational drugs during a public health emergency, communications with the FDA, and the Animal Model Qualification Program.

Animal Studies: The rule sets general expectations for animal studies including the types of animals used in investigations, study conduct, types of animal care interventions, and the submission of the study report and data.

Compliance Program: The FDA has established a Compliance Program for the Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies to ensure the quality and integrity of the data from animal studies. This includes inspections of study sites to verify the quality and integrity of the data, evaluations of various areas such as personnel, test and control articles, facilities, equipment, and records.

Safety Evaluation: While the Animal Rule focuses on efficacy, safety evaluation of products is not addressed in the rule. Products evaluated for effectiveness under subpart I of part 314 and subpart H of part 601 will be evaluated for safety under preexisting requirements for establishing the safety of new drug and biological products.

How Can Sponsors Navigate the Regulatory Requirements?

Product Sponsors can navigate the regulatory requirements of the Animal Rule by early and ongoing communication with FDA, understanding the Animal Rule, developing a comprehensive drug development plan, ensuring data integrity, and following the guidelines of FDA’s compliance and Animal Model Qualification Programs.

Establish early and ongoing communication with FDA: Sponsors should request and receive two meetings with the FDA - one to discuss proposed animal model development activities and a second meeting prior to initiating pivotal animal studies.

Understand the Animal Rule: The FDA provides guidance documents to help Sponsors understand the Animal Rule and its expectations for product development under the rule.

Develop a Product Development Plan: A well-structured development plan is crucial. The plan should include a through description of the product’s intended use, identification of the appropriate animal model(s), and design of adequate and well-controlled animal studies.

Ensure Data Integrity: Sponsors must ensure the integrity of data in animal studies by conducting the studies under Good Laboratory Practice (GLP) guidelines, performing data quality and integrity checks, and ensuring personnel training.

Comply with FDA’s Compliance Program: FDA has established a Compliance Program for Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies. Sponsors should ensure compliance with the program.

Understand the Animal Model Qualification Program: Sponsors should be aware of the Animal Model Qualification Program, which provides a framework for the qualification of animal models for use in testing the effectiveness of drugs or biological products under the Animal Rule.

ProPharma: Animal Rule Experts

ProPharma helps Sponsors understand the Animal Rule requirements and to design GLP-compliant animal studies to ensure compliance with FDA’s programs and regulatory requirements. We provide a range of services to support development and execution of a Product Development Plan (PDP) outlining development and regulatory strategy, major milestones, potential technical hurdles, and approximate timelines and costs through IND/CTA submission. We help Sponsors develop optimal study designs for nonclinical animal studies, as well as clinical studies as part of the IND submission. Our experts can help draft or review a Sponsor’s study designs and/or protocols for clinical studies required in the IND/CTA submission, taking into consideration the nature and extent of evidence required to demonstrate Proof-of

Concept regarding efficacy and safety outcomes, and anticipated regulatory agency expectations. We help Sponsors establish early and ongoing communications with regulators by preparing for and attending FDA meetings.

We have some of the most well-known and well-regarded industry, academic, and regulatory professionals in the world. They have played a leading role in the development and regulatory approval of hundreds of significant new products and pioneered some of the most innovative modern approaches to biomedical product development and regulatory review. The former pharmaceutical industry and regulatory agency senior executives who comprise the experts in the firm, possess an unsurpassed knowledge of the product development and regulatory environment. They are thoroughly familiar with the review expectations in various agency divisions and can guide Sponsors to successful marketing approval. 

The World's Leading Regulatory Consultancy

Interested in learning more? Contact us today to learn how our team of expert regulatory consultants can help with any and all of your global regulatory needs.


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