FDA typically requires safety and efficacy to be demonstrated in humans, but there are times when exposure of humans to toxic therapeutic substances may be impractical and ethically impossible (e.g., antidote for nerve gas treatment, nuclear threat, biological, chemical or substance that would otherwise causea life-threating condition or poisoning [e.g., snake venom, virus, industrial chemicals]). The FDA has released a newly revised update to its previously issued 2009 Guidance on this topic. Within this update, it states, “While addressing the topics covered in the 2009 draft, this revision covers a broader scope of issues for drugs developed under the Animal Rule. For example, new sections have been added related specifically to study conduct and data quality and integrity (section IV.B), development of vaccines (section VII.A), and development of cellular and gene therapies (section VII.B). There are new sections on FDA’s general expectations for animal studies related to, for example, animals used in investigations, types of animal care interventions, and study reports (section IV). There is also a new section on FDA’s general expectations regarding natural history studies (Appendix C).” The 53 page Draft Guidance can be found in its entirety here.
The FDA indicates that the only time they will permit the use of the Animal Rule is if all of the four criteria listed below are met:
1. There is a reasonably well-understood pathophysiological mechanism of the toxicity of the 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 for predicting the response in humans;
3. The animal study endpoint is clearly related to the desired benefit in humans, 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.
The Draft Guidance makes for some interesting and thought-provoking reading. Remember, the FDA does a case-by-case review as to whether to permit development of a product under this rule, but with the world as it is today, it may be possible that this document is unfortunately more reflective of the times in which we live.