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Animal Rule Summary

Final Guidance for Industry: Product Development Under the Animal Rule (PDF, 574 KB)

In assessing the sufficiency of animal data, FDA may take into account other data, including human data, available to the agency. Under this rule, FDA can rely on the evidence from animal studies to provide substantial evidence of the effectiveness of these products when:

  1. There is a reasonably well-understood pathophysiological mechanism of the toxicity of the chemical, biological, radiological, or nuclear substance and its prevention or substantial reduction by the product;
  2. The effect is demonstrated in more than one animal species expected to react with a response predictive for humans, unless the effect is demonstrated in a single animal species that represents a sufficiently well-characterized animal model (meaning the model has been adequately evaluated for its responsiveness) for predicting the response in humans;
  3. The animal study endpoint is clearly related to the desired benefit in humans, which is generally the enhancement of survival or prevention of major morbidity; and
  4. The data or information on the kinetics and pharmacodynamics of the product or other relevant data or information, in animals and humans, allows selection of an effective dose in humans.

These animal efficacy studies substitute for efficacy trials in humans, and therefore, the assessment of efficacy in animals should follow best practices for adequate and well-controlled human efficacy studies, with endpoints that demonstrate an important clinical benefit, generally the enhancement of survival or prevention of major morbidity. 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.).

Safety evaluation of products is not addressed in this 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. The agency believes that the safety of most of these products can be studied in human volunteers similar to the people who would be exposed to the product. FDA recognizes that some safety data, such as data on possible adverse interactions between the toxic substance itself and the new product, may not be available. This is not expected to keep the agency from making an adequate safety evaluation.

FDA’s procedures and standards for evaluating the safety of new drug and biological products are sufficiently flexible to provide for the safety evaluation of products evaluated for efficacy under 21 CFR subpart I of part 314 and subpart H of part 601. This rule will not apply if product approval can be based on standards described elsewhere in our regulations (e.g., accelerated approval based on human surrogate markers or clinical endpoints other than survival or irreversible morbidity).

This summary was taken from the introduction in the final regulation, New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible, Federal Register, Vol. 67, No. 105, Friday, May 31, 2002 (Federal Register notice).

Also see the revised final guidance Product Development Under the Animal Rule (PDF, 574 KB) published in October 2015. The revised guidance addresses a broader scope of issues for products developed under the Animal Rule, incorporates the learnings of considerable product development experience, and provides additional scientific and regulatory information to support a better understanding of the specific expectations for animal data intended to support approval or licensure of medical countermeasures. 

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