U.S. Food and Drug Administration

1. U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only. It was current when produced, but is no longer maintained and may be outdated.

2. Effects of the use of antimicrobial drugs in food producing animals on pathogen shedding:Summary ofCritical points Dr. David G. White Center for Veterinary Medicine VMAC Meeting-Pathogen Load January 23,2002

3. Relevant factors related to drug use and pathogen load on potential human health impacts • Mid 1970’s, 21 CFR 558.15 “studies” • sub-therapeutic uses • shedding and resistance components • 1998, Guidance for industry #78 • all uses of all classes of antimicrobial new animal drugs • rate and extent of development of resistance • changes in pathogen load • 2000, CVM meeting on pre-approval studies in antimicrobial resistance and pathogen load • pre-approval studies to evaluate potential microbial effects associated with antimicrobial drug use in food-producing animals(http://www.fda.gov/cvm/antimicrobial/oldmeet.htm) • j

4. Relevant factors related to drug use and pathogen load on potential human health impacts • A consideration of the potential microbiological effects of antimicrobial new animal drugs has been identified as a significant component of the animal drug safety evaluation process • The lessons learned from the “558.15 studies” along with 20 years of advancement in scientific knowledge, are important factors for helping to develop appropriate methodologies for evaluating the relevant microbiological effects associated with the use of antimicrobial drugs in food-producing animals

5. VMAC pathogen load presentationsJanuary, 23, 2002 • Dr. Stephen Sundlof, CVM, Regulatory history • Dr. Jeffrey Gilbert, CVM: History of 21 CFR 558.15 “studies” • Dr. Tom Shryock, Elanco: Conduct of shedding studies • Dr. Jeff Gray, USDA: Design considerations • Dr. Mike Goodman, Exponent: Literature review • Dr. Scott McEwen, Univ. of Guelph: Epidemiological evidence • Dr. Richard Isaacson, Univ. of Minnesota: Pathogen shedding • Dr. Barbara Masters, USDA: PR/HAACP • Dr. Mark Robinson, CVM: Human food safety evaluation

6. 21 CFR 558.15 “Studies”regulatory perspective • Dr. Jeff Gilbert presented a brief history regarding submitted sponsor pre-approval studies to support microbiological safety of antimicrobial drugs • study design and examined parameters • integrity measurements • study results • identified problems • based on policy and regulation of the time

7. 21 CFR 558.15 “Studies”sponsor perspective • Dr. Tom Shryock presented industry experience with studies • study design and interpretation • study results • identified problems and limitations • relevance

8. Pathogen load study design considerations • Dr. Jeff Gray presented information regarding pathogen load study designs • organism • study design • measuring effects • confounding factors

9. Exponent literature review • CVM contracted with Exponent to conduct a review of published literature on the effect of using antimicrobials in food-producing animals on pathogen load • Dr. Mike Goodman presented summary of Exponent report • located athttp://www.fda.gov/cvm/antimicrobial/PathRpt.pdf • 33 literature databases were searched • challenge or observational studies • limited data

10. Epidemiological evidence of pathogen load effects • Dr. Scott McEwen presented an overview of relevant epidemiological information related to food animal studies • human studies • companion animal studies • food animal studies • study results

11. Pathogen shedding issues • Dr. Richard Isaacson presented information relevant to shedding of pathogens in food animals • study design • bacterial detection • culture methods • confounding factors • take home points

12. PR/HAACP • Dr. Barbara Masters presented information with regards to USDA/FSIS PR/HAACP • history • regulatory requirements • implementation • performance criteria • performance standards

13. Human food safety evaluation • Dr. Mark Robinson presented information describing evaluation of sponsor generated data • relevance to public health • identify and mitigate potential adverse human health effects • “safety” of drug product

14. CVM - Pathogen load • CVM recognizes that scientific information in this area is limited and acknowledges the concerns raised at the February 2000 public meeting • CVM contracted with Exponent to conduct a literature review on the subject to gather additional information • Today’s VMAC represents our ongoing efforts to look at the issue of pathogen load and to develop appropriate policy in this area • CVM is seeking recommendations from the VMAC on the issue of evaluating potential antimicrobial drug effects on pathogen load in food-producing animals as part of the new animal drug application process

15. Open public session (am) Presentation of questions to VMAC Committee deliberations Meeting summary Special thanks: William Flynn Patrick McDermott Charles Eastin Karen Lampe Jeff Gilbert Aleta Sindelar Mark Robinson Bert Mitchell VMAC pathogen load January, 24, 2002