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

Relating Food Animal and Relating Food Animal and Human Antimicrobial UseHuman Antimicrobial Use

Comments to the FDA Anti-Infective Drugs Advisory CommitteeComments to the FDA Anti-Infective Drugs Advisory Committee on behalf of theon behalf of the

American Veterinary Medical AssociationAmerican Veterinary Medical Association

Mike Apley, DVM, PhDMike Apley, DVM, PhDDepartment of Veterinary Diagnostic and Production Animal Department of Veterinary Diagnostic and Production Animal

MedicineMedicineIowa State UniversityIowa State University

Gaithersburg, MD, January 9, 2003Gaithersburg, MD, January 9, 2003

The AVMA has presented The AVMA has presented written and public comments written and public comments

on Docket Number 98D-on Docket Number 98D-1146, Draft Guidance for 1146, Draft Guidance for

Industry #152.Industry #152.Comments in this presentation Comments in this presentation

focus on the ranking of focus on the ranking of antimicrobial drugs according to antimicrobial drugs according to

their importance in human their importance in human medicine as contained in Guidance medicine as contained in Guidance

#152.#152.

Antimicrobial RankingAntimicrobial Ranking

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drugs with regard to their relative importance in human medicine as importance in human medicine as contained in draft Guidance #152.contained in draft Guidance #152.

Antimicrobials in Food Antimicrobials in Food AnimalsAnimals

Food Animal Veterinarians rely on Food Animal Veterinarians rely on preventive and therapeutic strategies preventive and therapeutic strategies to maintain the health of food animals.to maintain the health of food animals.

Antimicrobials are essential for Antimicrobials are essential for addressing disease in food animals in addressing disease in food animals in order to relieve animal suffering and order to relieve animal suffering and conserve livestock resources.conserve livestock resources.

Healthy animals are the basis for a Healthy animals are the basis for a healthy food supply.healthy food supply.

Antimicrobial RankingAntimicrobial Ranking The antimicrobial ranking section of The antimicrobial ranking section of

Guidance #152 is especially critical Guidance #152 is especially critical because the rankings are considered because the rankings are considered when completing two parts of the when completing two parts of the three-part qualitative risk assessment three-part qualitative risk assessment outlined in Guidance #152.outlined in Guidance #152. Hazard identificationHazard identification Consequence assessmentConsequence assessment

Why the AVMA is ConcernedWhy the AVMA is Concerned

GuidanceGuidance #152 is composed of #152 is composed of multiple required input categories multiple required input categories that must be categorized as being of that must be categorized as being of low, medium, or high risk.low, medium, or high risk.

For many of the primary categories, For many of the primary categories, there is no defined method to there is no defined method to determine the degree of risk.determine the degree of risk.


If the FDA determines there is If the FDA determines there is inadequate information to assign a inadequate information to assign a risk classification in an input risk classification in an input category, then the most conservative category, then the most conservative assessment (high risk) is assigned.assessment (high risk) is assigned.

The result is a document heavily The result is a document heavily biased towards the concept that biased towards the concept that there are no potential adverse effects there are no potential adverse effects from unnecessary restriction of from unnecessary restriction of antimicrobial use in food animals.antimicrobial use in food animals.


This bias is accentuated further when This bias is accentuated further when antimicrobials are ranked on the antimicrobials are ranked on the basis of human therapeutic basis of human therapeutic applications with no demonstrated applications with no demonstrated relationship to food animals.relationship to food animals.

The context within which the drugs The context within which the drugs should be ranked is defined in should be ranked is defined in Guidance #152. Guidance #152.

Guidance #152 HazardGuidance #152 Hazard

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

Guidance #152 RiskGuidance #152 Risk

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

Antimicrobial RankingAntimicrobial Ranking In Guidance #152, food animal and In Guidance #152, food animal and

human antimicrobial use are human antimicrobial use are relatedrelated through “through “a specified animal-derived a specified animal-derived food commodityfood commodity”.”.

Therefore, the AVMA believes that Therefore, the AVMA believes that the antimicrobial drug rankings in the antimicrobial drug rankings in Guidance #152 should consider only Guidance #152 should consider only those bacteria or resistance those bacteria or resistance determinants that are determinants that are food bornefood borne..


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

The AVMA asks for The AVMA asks for justification of antimicrobial justification of antimicrobial

rankings based on the rankings based on the following disease/organism following disease/organism

combinations in a document combinations in a document intended to address intended to address

resistance relationships resistance relationships through food borne channels.through food borne channels.

Examples of Ranking Examples of Ranking JustificationsJustifications

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

Additional Ranking Additional Ranking JustificationsJustifications

gonorrhea in pregnant women; gonorrhea in pregnant women; tuberculosis; tuberculosis; pneumonia caused by pneumonia caused by Legionella Legionella

pneumophilapneumophila;; empirical treatment of bacterial empirical treatment of bacterial

meningitis,meningitis, endocarditis, osteomyelitis, or endocarditis, osteomyelitis, or

pneumonia caused by methicillin-pneumonia caused by methicillin-resistant resistant Staphylococcus aureusStaphylococcus aureus (MRSA); (MRSA);

Additional Ranking Additional Ranking JustificationsJustifications

post-exposure prophylaxis of invasive post-exposure prophylaxis of invasive disease caused by disease caused by Neisseria Neisseria meningitidesmeningitides;;

Pseudomonas aeruginosaPseudomonas aeruginosa infections. infections.


Guidance document #152 does not Guidance document #152 does not provide the specific disease provide the specific disease justification(s) for the rankings of justification(s) for the rankings of each drug.each drug.

A representative of the FDA stated A representative of the FDA stated during the public meeting on October during the public meeting on October 2, 2002 “There is also a degree of 2, 2002 “There is also a degree of subjectivity in these [ranking] subjectivity in these [ranking] determinations”.determinations”.

The AVMA requests that the The AVMA requests that the justification of the assigned justification of the assigned

rankings of the drugs be rankings of the drugs be made fully transparent, and made fully transparent, and

that opportunity for comment that opportunity for comment on these justifications be on these justifications be

provided prior to finalization provided prior to finalization of the guidance documentof the guidance document

Documents

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