1. Infrastructure for FDA Registration of Erythromycin Christine M. Moffitt University of Idaho Idaho Cooperative Fish and Wildlife Research Unit Christine M. Moffitt University of Idaho Idaho Cooperative Fish and Wildlife Research Unit

2. Background Research Conducted by the University of Idaho and Cooperating Columbia Basin Hatcheries to support FDA Approval of Erythromycin to Control Bacterial Kidney Disease under Investigational New Animal Drug (INAD) permit 6013

3. Past Milestones Completion and Acceptance by FDA of Required Studies –Efficacy –Target Animal Safety –Residue Depletions Completion and Acceptance by FDA of Required Studies –Efficacy –Target Animal Safety –Residue Depletions

4. ISSUES UNRESOLVED Concerns Originating in the Centers for Disease Control Regarding Risks of Resistant Microorganisms Associated with Antibiotic Therapy in Animals Little Understanding of Aquaculture and Associated Risks Concerns Originating in the Centers for Disease Control Regarding Risks of Resistant Microorganisms Associated with Antibiotic Therapy in Animals Little Understanding of Aquaculture and Associated Risks

5. Project Objectives 1. Provide an infrastructure to keep erythromycin registration efforts viable in the Columbia River Basin, while required studies are conducted.

6. Hatcheries or Release Sites that Used Erythromycin 1992 +

7. Percent of Total Use Over Time

8. Percent of Hatcheries Using Erythromycin IntervalNumber1-2 yrs 3-5 yrs 1992- 1996 9264.535.5 1997- 2001 7665.234.8

9. Objective 2 Conduct experiments and design monitoring to understand the extent of erythromycin resistant microflora in the GI tract of fish following treatment with erythromycin

10. FDA Specific Questions to be Addressed Will Bacterial Drug Resistance During Treatment Extend into Post Treatment Phase? Will Resistance Persist in Fish until Release? Will Resistance Persist in Fish that Do not Migrate to the Ocean? Will Bacterial Drug Resistance During Treatment Extend into Post Treatment Phase? Will Resistance Persist in Fish until Release? Will Resistance Persist in Fish that Do not Migrate to the Ocean?

11. Frequent Users in Past Decade

12. Mg/yearling released <50 50-100 >100

13. Objective 3 Conduct experiments to address the fate of erythromycin in sediment ponds with a history of erythromycin treatment

14. Specific FDA Questions What are Patterns of Bacterial Resistance in Sediment Ponds Receiving Effluents from Salmonid Rearing Systems with a History of Erythromycin versus those Without? What are the Patterns in Fish Near Effluents ? What are Patterns of Bacterial Resistance in Sediment Ponds Receiving Effluents from Salmonid Rearing Systems with a History of Erythromycin versus those Without? What are the Patterns in Fish Near Effluents ?

15. Mg/fish Changes Over Time Decrease No Trend Increased

16. Objective 4 Provide submittals to FDA that detail results and publish in peer-reviewed journals the results of key studies accomplished during drug approval.

17. Justification Erythromycin is Needed for Effective Fish Health Management Must Demonstrate Progress or INAD will be Revoked Issues and Approaches to Understand Risks will be Useful to Understanding Hatchery Impact on Fish Populations within the Larger Landscape.