1. Antibiotic Resistance: Incentives for Antimicrobial Development Mark J Goldberger MD MPH CDER/FDA

2. Current situation Problem: –Antibiotic resistance is increasing Solutions: –Facilitate development of antimicrobial therapy for resistance and related claims –Preserve usefulness of current and new drugs

3. Issues in Development Regulatory/clinical trial Scientific/medical Economic

4. Regulatory Tools Early Guidance –Formal and informal communication –Advisory committee input Regulatory Tools –Subparts “E” & “H” –Fast Track designation –Exclusivity

5. Clinical Trial Issues Reduce the size of the clinical trial program Address the tradeoff between our ability to assess effectiveness and the resources required to perform a trial. Substituting quality for quantity in at least some clinical studies Strengthening the link to clinical inference –How studies and data fit together as a package

6. Consequences of the Preceding Serious illness = Expedited development Expedited development = Reduced costs Does expedited development = Less certainty re benefit and risk? Consequences of uncertainty

7. Scientific Issues Validation of surrogates The use of pre-clinical and early clinical trial data in combination with clinical trial data The role of infections due to susceptible organisms in the study of drugs for resistance claims Enhancing early discovery

9. Economic Incentives Exclusivity –Orphan Drugs: Seven years marketing exclusivity –Waxman-Hatch: Now available for “new” antibiotics –Pediatric Exclusivity: Six additional months added on to existing exclusivity

11. Other Potential Economic Incentives Expanding eligibility for orphan designation Bioshield like purchase arrangements “Wildcard Exclusivity” Other exclusivity or enhanced patent protection

12. Economic Downside to Antimicrobial Development Short course Rx Highly effective Rx Need is greatest for resistant and related infections: Market is most attractive for infections in the primary care setting Contrast with HIV Rx

13. An Unresolved Dilemma There is a basic tension between encouraging antimicrobial development and preserving the usefulness of current and new drugs Absent sufficient balance between these activities, adequate investment may not occur or the benefits of such investment may be short-lived

14. Limits of our Authority We can’t develop a drug New types of exclusivity/patent protection would require new legislation Reminder: Promotional claims derive from statements in labeling