1. Relating Food Animal and Human Antimicrobial Use Comments to the FDA Anti-Infective Drugs Advisory Committee on behalf of the on behalf of the American Veterinary Medical Association Mike Apley, DVM, PhD Department of Veterinary Diagnostic and Production Animal Medicine Iowa State University Gaithersburg, MD, January 9, 2003

2. The AVMA has presented written and public comments on Docket Number 98D-1146, Draft Guidance for Industry #152. Comments in this presentation focus on the ranking of antimicrobial drugs according to their importance in human medicine as contained in Guidance #152.

3. Antimicrobial Ranking The AVMA has a significant concern with the ranking of antimicrobial drugs with regard to their relative importance in human medicine as contained in draft Guidance #152. The AVMA has a significant concern with the ranking of antimicrobial drugs with regard to their relative importance in human medicine as contained in draft Guidance #152.

4. Antimicrobials in Food Animals Food Animal Veterinarians rely on preventive and therapeutic strategies to maintain the health of food animals. Food Animal Veterinarians rely on preventive and therapeutic strategies to maintain the health of food animals. Antimicrobials are essential for addressing disease in food animals in order to relieve animal suffering and conserve livestock resources. Antimicrobials are essential for addressing disease in food animals in order to relieve animal suffering and conserve livestock resources. Healthy animals are the basis for a healthy food supply. Healthy animals are the basis for a healthy food supply.

5. Antimicrobial Ranking The antimicrobial ranking section of Guidance #152 is especially critical because the rankings are considered when completing two parts of the three-part qualitative risk assessment outlined in Guidance #152. The antimicrobial ranking section of Guidance #152 is especially critical because the rankings are considered when completing two parts of the three-part qualitative risk assessment outlined in Guidance #152. Hazard identification Hazard identification Consequence assessment Consequence assessment

6. Why the AVMA is Concerned Guidance #152 is composed of multiple required input categories that must be categorized as being of low, medium, or high risk. Guidance #152 is composed of multiple required input categories that must be categorized as being of low, medium, or high risk. For many of the primary categories, there is no defined method to determine the degree of risk. For many of the primary categories, there is no defined method to determine the degree of risk.

7. Why the AVMA is Concerned If the FDA determines there is inadequate information to assign a risk classification in an input category, then the most conservative assessment (high risk) is assigned. If the FDA determines there is inadequate information to assign a risk classification in an input category, then the most conservative assessment (high risk) is assigned. The result is a document heavily biased towards the concept that there are no potential adverse effects from unnecessary restriction of antimicrobial use in food animals. The result is a document heavily biased towards the concept that there are no potential adverse effects from unnecessary restriction of antimicrobial use in food animals.

8. Why the AVMA is Concerned This bias is accentuated further when antimicrobials are ranked on the basis of human therapeutic applications with no demonstrated relationship to food animals. This bias is accentuated further when antimicrobials are ranked on the basis of human therapeutic applications with no demonstrated relationship to food animals. The context within which the drugs should be ranked is defined in Guidance #152. The context within which the drugs should be ranked is defined in Guidance #152.

9. Guidance #152 Hazard The hazard in Guidance #152 is defined “as human illness that is caused by a specified antimicrobial-resistant bacteria, is attributable to a specified animal- derived food commodity, and is treated with the human antimicrobial drug of interest.” [Emphasis added] The hazard in Guidance #152 is defined “as human illness that is caused by a specified antimicrobial-resistant bacteria, is attributable to a specified animal- derived food commodity, and is treated with the human antimicrobial drug of interest.” [Emphasis added]

10. Guidance #152 Risk The risk in Guidance #152 is defined “as the probability that human illness is caused by a specified antimicrobial - resistant bacteria, is attributable to a specified animal-derived food commodity, and is treated with the human antimicrobial drug of interest.” [Emphasis added] The risk in Guidance #152 is defined “as the probability that human illness is caused by a specified antimicrobial - resistant bacteria, is attributable to a specified animal-derived food commodity, and is treated with the human antimicrobial drug of interest.” [Emphasis added]

11. Antimicrobial Ranking In Guidance #152, food animal and human antimicrobial use are related through “a specified animal-derived food commodity”. In Guidance #152, food animal and human antimicrobial use are related through “a specified animal-derived food commodity”. Therefore, the AVMA believes that the antimicrobial drug rankings in Guidance #152 should consider only those bacteria or resistance determinants that are food borne. Therefore, the AVMA believes that the antimicrobial drug rankings in Guidance #152 should consider only those bacteria or resistance determinants that are food borne.

12. Antimicrobial Ranking Antimicrobial drug rankings justified on the importance for treatment of other than food borne bacterial disease or disease involving food borne resistance determinants should not be included in Guidance #152. Antimicrobial drug rankings justified on the importance for treatment of other than food borne bacterial disease or disease involving food borne resistance determinants should not be included in Guidance #152.

13. The AVMA asks for justification of antimicrobial rankings based on the following disease/organism combinations in a document intended to address resistance relationships through food borne channels.

14. Examples of Ranking Justifications Ranking justifications for these diseases and/or organisms are either contained in Guidance #152 or were presented in discussion at the public meeting. Ranking justifications for these diseases and/or organisms are either contained in Guidance #152 or were presented in discussion at the public meeting. acute bacterial meningitis; acute bacterial meningitis; neurosyphilis in pregnant women; neurosyphilis in pregnant women;

15. Additional Ranking Justifications gonorrhea in pregnant women; gonorrhea in pregnant women; tuberculosis; tuberculosis; pneumonia caused by Legionella pneumophila; pneumonia caused by Legionella pneumophila; empirical treatment of bacterial meningitis, empirical treatment of bacterial meningitis, endocarditis, osteomyelitis, or pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA); endocarditis, osteomyelitis, or pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA);

16. Additional Ranking Justifications post-exposure prophylaxis of invasive disease caused by Neisseria meningitides; post-exposure prophylaxis of invasive disease caused by Neisseria meningitides; Pseudomonas aeruginosa infections. Pseudomonas aeruginosa infections.

17. Antimicrobial Ranking Guidance document #152 does not provide the specific disease justification(s) for the rankings of each drug. Guidance document #152 does not provide the specific disease justification(s) for the rankings of each drug. A representative of the FDA stated during the public meeting on October 2, 2002 “There is also a degree of subjectivity in these [ranking] determinations”. A representative of the FDA stated during the public meeting on October 2, 2002 “There is also a degree of subjectivity in these [ranking] determinations”.

18. The AVMA requests that the justification of the assigned rankings of the drugs be made fully transparent, and that opportunity for comment on these justifications be provided prior to finalization of the guidance document