Emergency Preparedness and Response
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Encouraging Development of Animal Models for Evaluation and Qualification
Background Qs & As and Highlights of FDA Efforts Under Way
Q: What are the hurdles to medical countermeasure development and approval?
A key hurdle is the limited human data available to assess a medical countermeasure's effectiveness.
Q: Why are the data limited?
Most of the diseases or conditions under consideration, like infections such as anthrax, smallpox, and plague, do not occur naturally. If they do occur, the number of people infected is so small that clinical trials are infeasible. For threats such as radiation or toxic chemicals ( e.g., cyanide), accidental exposures can provide limited human data, however, clinical trials to study efficacy are not feasible — It would be unethical to intentionally infect or to expose people to radiation or toxic chemicals to test possible treatments to see if they work.
Q: Then how can a product's effectiveness in people be demonstrated?
Medical product sponsors will have to show that their product works (effectiveness) in studies conducted in animals that model the human disease. Then, FDA will have to rely on these data as substantial evidence of product effectiveness during regulatory decision making. For many of the threat agents, animal models that simulate critical features of the human disease or condition have not been developed. FDA is encouraging the qualification*of existing models that adequately simulate the human disease or condition and new animal models as they are developed.
Q: What can be done to address this problem?
FDA is working to:
- Spur development and evaluation of product-independent animal models for qualification
- Provide guidance to current and prospective product sponsors on issues related to animal models for medical countermeasures that will be developed under the Animal Rule
- Make relevant information easily accessible to prospective product sponsors (see web site Program for Drug Development Tools Qualification)
Highlights of FDA Activities to Encourage Development, Qualification,
and Use of Animal Models
Animal rule
In May 2002, FDA issued the final rule New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible1. The regulation allows appropriate studies in animals in certain cases to provide substantial evidence of the effectiveness of new drug and biological products used to reduce or prevent the toxicity of chemical, biological, radiological, or nuclear (CBRN) substances. See a high-level summary taken from the final regulation.
Animal model draft guidance
In January 2009, FDA issued a draft guidance Animal Models—Essential Elements to Address Efficacy Under the Animal Rule3 to provide information to potential sponsors (industry, academia, and government) on the development of animal models to study efficacy. FDA received numerous comments during the public comment period following publication of the draft and at the November 2010 public meeting on the draft guidance. To address the comments and revise the guidance, FDA created a multi-disciplinary, multi-Center team that is carefully considering the comments expressed by the community, including requests to expand the scope of the guidance. FDA intends to publish the guidance as a revised draft for public comment. The revised and expanded guidance should provide 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.
Animal model qualification process
In October 2010, FDA published the draft guidance Qualification Process for Drug Development Tools4, which describes the qualification process for drug development tools (DDTs) intended for potential use in drug development programs. Examples of DDTs include biomarkers, of which animal models is a subset. Both of these DDTs are important in medical product development, especially for medical countermeasures developed under the Animal Rule. Among other things, the guidance provides a framework for interactions between FDA and DDT submitters to identify the data needed to support qualification of a DDT. The guidance also creates a mechanism for formal review by FDA to qualify a DDT.
*The guidance defines qualification as a conclusion that within the stated context of use, the “results of assessment with a DDT can be relied on to have a specific interpretation and application in drug development and regulatory decision-making.”
FDA is developing an Animal Model Qualification Program that will be consistent with the process described in the DDT guidance (once finalized) to enable the qualification of product-independent animal models within a context of use to evaluate product efficacy under the Animal Rule.
For more information, contact us at AskMCMi@fda.hhs.gov
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