1. Bioterrorism: Changing Priorities in Medical Training and Research Art Anderson MD Colonel US Army Medical Corps Director, Office of Human Use and Ethics, USAMRIID This presentation represents the views of the author. The information or content presented does not represent the official position or policy of the U.S. Army Medical Research and Materiel Command, the U.S. Army Medical Department, the Department of Defense, or the U.S. Government. RPP-03-104

2. Bioterrorism: Changing Priorities  Bioterrorism in the US was no longer theoretical after 2001  DHS, was created for domestic security and countermeasures  R&D for Biodefense medical countermeasures under DHHS  Present Bioterrorism response resembles US response to threat of BioWarfare with WWII

3. Then - 1942

4. NBACC Hub-and-Spoke Concept USAMRMC USAMRIID NIAID FBI CDC Training HS Institute SNL LLNL EML USUHS HSARPA DHS NBACC USDA ARS Plant USDA RAS Animal FDA AFMIC Academia Private Sector NRC/ National Academies USDA Plum Island LANL SBCCOM DoD Dugway P.G. DARPA AFRRI HHS WRAIR NMRC AFIP NSTC Biodefense Research Coordinating Committee USDA CIA National Biodefense Analysis and Countermeasures Centers Post 9/11/01 Now

5. Bioterrorism: Changing Priorities in Medical Training and Research  Translation of biosafety, biosurety, security and bioethical research practices from closed military installations to open university campuses will require specialized training, personnel and expensive infrastructure.  Providing for worker safety in high-hazard containment may produce ethical dilemmas with regard to voluntary use of IND products for prophylaxis and treatment, vs restricting access and policing safety practices.  Involvement of the larger academic community will hasten development of countermeasures and speed up spin-offs for the public sector, but at a cost of increasing vigilance, and security, thereby restricting openness on campuses

6. Medical Ethics After 9/11/2001: Does it require Rethinking?  The US Health Care System Has Not Faced Threats of Bioterrorism or Major Epidemics since before WW I I  The Military has been preparing for protecting troops against BioWarfare since 1943 but it was assumed that it would happen “over there” and not inside the US  In a national bioterror emergency, time taken to adhere to medical research laws, regulations and rules may interfere with effective use of “pipeline” drugs, vaccines and devices when needed immediately by responders

7. Ethical Analysis vs Rules & Laws  Common Rule Regulates Research based on Ethical Principles but applied as Rules blocked if Ethical Analysis result differs from the Rule  FDA Regulates Product FD&CA Law & FDA regulations control development, labeling, marketing and use of drugs, biologics & devices FDA defines use of product labeled IND / IDE as Research irrespective of intended use  Nuremberg Code provides principles that may be applied in Ethical Analyses for Biodefense Research

8. A National Biodefense Program Produces an Ethical Dichotomy:  Overarching circumstances may effect what kinds of actions ethical analyses may determine are preferred.  Respect the rights and welfare of subjects who participate in research designed to discover, validate and gain FDA marketing approval for products to be used in prevention and treatment of possible bioterrorism casualties. Versus  Urgent need to use unapproved products reasonably thought to be beneficial for protection from - or immediate treatment of bioterrorism when there is an emergency and no approved alternatives are available.

9. Big Footprint Small Benefit IND SMART Team vs Iraq Reality Study Site Constantly Moving

10. Legislation Was Needed to Overcome Obstacles of IND format in Biodefense  The “investigational” label and structured research format interferes with subject acceptance of products because of perception of experiment when treatment is intended.  Difficulties meeting IND/GCP regulatory requirements may cause DoD to deviate from FDA requirements or fail to successfully accomplish force health protection.  Seek “streamlined IND” from FDA for rapid licensure of advanced products with utility or potential utility.  Emergency use of key FDA-unapproved drugs is possible for “pipeline” products via Project BioShield.

11. Project Bioshield: 1. Establish secure funding source for purchase of critical biomedical countermeasures - approved 2. Increase authorities and flexibility for NIH / NIAID to expedite research and development of critical biomedical countermeasures 3. Establish an FDA Emergency Use Authorization for critical biomedical countermeasures Three-pronged program: to accelerate the process of research, development, purchase, and availability of effective countermeasures against agents of bioterror or biowarfare

12. Project BioShield : Benefits  CDC, HHS & DoD may use HHS Project BioShield procedures if legislation is approved Passed: H.R. 2122 Project Bioshield Act - July 16 2003 Passed: S. 15 Project BioShield Act - May 19 2004 President Signed : Public Law No: 108-276 July 21 2004 Presented: H.R. 4258 Rapid Pathogen Identification to Delivery of Cures Act - May 3, 2004 Presented: S.1873 Biodefense and Pandemic Vaccine and Drug Development Act of 2005 – IS Oct 17, 2005; RS Oct 24, 2005  These legislative Acts resolve the dilemma and the dichotomy that is associated with widespread use of FDA- unapproved products in civilians for national biodefense or in soldiers facing war hazards

13. Arthur O. Anderson MD Director, Office of Human Use and Ethics US Army Medical Research Institute of Infectious Diseases Fort Detrick, Frederick MD 21702-5011