Animal Models for Assessing Countermeasures to Bioterrorism Agents

Animal Models for Assessing Countermeasures This issue evaluates how well the existing TMT-employed or candidate animal models reflect the pathophysiology, clinical picture, and treatment of human disease as related to the agents of interest. The report also evaluates alternatives to the use of animal models based on the premise of the Three Rs.

The report addresses the process and/or feasibility of developing new animal models for critical biodefense research, placing emphasis on the need for a robust and expeditious validation process in terms of the FDA's Animal Rule.

Contents
SUMMARY
1 INTRODUCTION
The Nature of Threat
Addressing the Unknown Threat through the Transformational Medical Technologies Initiative
Statement of Task
Approach by the Committee
References
2 EVALUATION OF CURRENT AND FUTURE TMT-USED ANIMAL MODELS
Animal Models Are Analogous, Not Homologous Systems
Considerations for Animal Models for Countermeasure Development
Filoviruses
Tularemia
Anthrax
Lessons Learned from Developing Animal Models for Therapeutic Purposes against Biothreat Agents
References
3 ETHICAL AND REGULATORY CHALLENGES IN THE DEVELOPMENT OF COUNTERMEASURES
History of the Animal Rule and Ethical Considerations
The Low Approval Rate to Date under the Animal Rule
Regulation of Drug Development
References
4 DEVELOPING NEW ANIMAL MODELS FOR BIODEFENSE RESEARCH
Use of Human Data to Improve the Value of Animal Models
Interactions with the Food and Drug Administration
“Validation” of Animal Models for Biodefense Research
Comparative Biology and Compartmentalization in Animal Model Development
Optimizing Current Animal Models
References
5 ALTERNATIVE APPROACHES TO ANIMAL TESTING FOR BIODEFENSE COUNTERMEASURES
General Principles of Alternative Approaches
Animal Efficacy Studies Are Clinical Trials
In Vitro Tools and Replacement Strategies
Promises and Challenges for the Future
References,
APPENDICES
A THE ANIMAL RULE
B DRAFT GUIDANCE TO INDUSTRY: ANIMAL MODELS – ESSENTIAL ELEMENTS TO ADDRESS EFFICACY UNDER THE ANIMAL RULE
C DEVELOPING ANIMAL MODELS FOR USE IN ANIMAL RULE LICENSURE: THE NIAID APPROACH
D PRESENTATIONS TO THE COMMITTEE
E STATEMENT OF TASK
F ABOUT THE AUTHORS