biodefense animal models will inform future efforts in less mature or non-biodefense animal models. It is important that future models be developed and studies performed in the most appropriate facilities—early proof of concept models may not be the best utilization of resources if performed in the expensive and limited environment of a GLP facility. It would be highly appropriate to develop animal models in research facilities and successfully transfer them to a fully compliant GLP environment, and a history of smooth transition from research to GLP facilities will help establish a greater level of comfort in the appropriate placement of animal studies by the product development community. Research laboratories need to consider early choices that may impact the transferability of models, such as the creation of master and working banks of pathogens and standardization and definition of limits of procedures, in order to successfully transfer models to a GLP environment. The term “GLP-like” is often derided as meaningless, but it can be difficult to transfer a model from research laboratory practices to GLP without going through an intermediate of good laboratory habits and documentation, with an eye toward the ultimate goal. The current state of animal model development is progressive in nature, approached by incremental advances rather than cumulative advancements all in one study. Other approaches may be feasible, but are uncharted regarding the final goal of successful implementation in regulatory decisions.

7. SUMMARY

Over the past seven years, NIAID has developed an extensive program devoted to animal models that are coordinated with, but not direct results of, product development efforts. The product-neutral nature of NIAID’s animal model program has focused on developing the best possible animal models, without the potentially competing interest of furthering a product. This approach has been very productive and has tremendously helped the regulatory framework for assessing product efficacy. NIAID’s models are assessed as models in their own right, without a concomitant assessment of a product. NIAID’s objective approach to animal model development, along with a high level of investment, has been very successful and should be viewed as the standard when approaching Animal Rule efficacy to support medical countermeasures for biological threats.

“Nothing happens quite by chance. It’s a question of accretion of information and experience.”

Jonas Salk

REFERENCES:

Friedlander AM, SL Welkos, MLM Pitt, JW Ezzell, PL Worsham, KJ Rose, BE Ivins, JR Lowe, GB Howe, P Mikesell and WB Lawrence, “Postexposure Prophylaxis Against Experimental Inhalational Anthrax,” J. Infectious Diseases, 167: 1239-42, 1993.

Vietri NJ, BK Purcell, JV Lawler, EK Leffel, P Rico, CS Gamble, NA Twenhafel, BE Ivins, HS Heine, R Sheeler, ME Wright and AM Friedlander, “Short-Course Postexposure Antibiotic Prophylaxis Combined with Vaccination Protects Against Experimental Inhalational Anthrax,” Proc. Natl. Acad. Sci., 103: 7813-7816, 2006.

ACKNOWLEDGEMENTS

The conclusions in this white paper are based upon projects managed by a number of people in the Office of Biodefense Research Affairs: Ken Cremer, Martin Crumrine, Kristin DeBord, Robert Johnson, Freyja Lynn, Tracy MacGill, Ed Nuzum, Blaire Osborn, and Thames Pickett. Thanks to Rose Aurigemma, Sue Garges, Irene Glowinski, and Mike Kurilla for critical reading of this manuscript.



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