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U.S. Department of Health and Human Services

Animal & Veterinary

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Draft Questions for Consideration for Panel Discussion and Public Comment

January 5, 2001 (revisions January 9, 2001)

The following questions are provided to stimulate discussion during the various panel discussion periods and public comment periods scheduled for the January 22-24, 2001, public meeting entitled, Use of Antimicrobial Drugs in Food Animals and the Establishment of Regulatory Thresholds on Antimicrobial Resistance. Although discussion of all relevant concerns and questions is encouraged, CVM requests consideration of the questions listed below during the respective panel discussion and comment periods.

Alternatively, comments regarding these questions, or any comments regarding the threshold discussion document or public meeting, may be submitted in writing by April 9, 2001. Written comments should refer to Docket # 00D-1677 and be submitted to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: William T. Flynn, Center for Veterinary Medicine (HFV-100), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-827-7570, e-mail at wflynn@cvm.fda.gov.

Session 2: Use of Antimicrobial Drugs in Food Animals

The establishment of regulatory thresholds on antimicrobial resistance requires a consideration of some quantifiable measure of the potential human health impact of concern. The CVM discussion document describes a human health threshold as the unacceptable level of human health impact associated with the use of an antimicrobial drug in food-producing animals. When considering potential human health impacts for the purpose of establishing regulatory thresholds, CVM believes that it is important to include in the discussion some consideration of all impacts, both positive and negative, associated with the use of these drugs in food animals. Therefore, in this session, we are interested in public feedback on the benefits of antimicrobial use in food animals and whether the potential level of unacceptable human health impact should be consistent for all antimicrobial drugs used in food animals or should vary. The following questions are offered for consideration although general comments would also be appreciated:

  1. What are the benefits of antimicrobial use in:

    • Young/growing food animals
    • Mature food animals
  2. If thresholds are set, should human health thresholds be consistent for all antimicrobial drugs used in animals or should they vary according to the importance of the antimicrobial drug to human medicine?
  3. If you believe human health thresholds should vary, please comment in general terms on whether the levels should be greater or smaller for the following categories of importance of the antimicrobial drug to human medicine:

    • Important antimicrobial drugs in human medicine for which alternatives are limited
    • Important antimicrobial drugs in human medicine for which alternatives are available
    • Antimicrobial drugs that have limited use in human medicine
  4. Other comments
Session 3: Establishing Human Health Thresholds
  1. As described in the CVM threshold document, the relevant human health concern is considered to be an unacceptable increase in the prevalence of human infections that are treated with the antimicrobial drug of concern and are caused by bacteria resistant to that drug due to the use of an antimicrobial drug in animals. Based on the current safety standard, an "unacceptable increase" is considered that level at which there is no longer reasonable certainty that there is no harm to human health.
  2. In order for the approach described in the CVM document to be consistent with the current safety standard, human health thresholds would need to be set that are consistent with there being "a reasonable certainty of no harm." Historically, the probability of one in a million (10-6) has been used as the risk standard for insignificant risk set in the regulations for animal drug carcinogens. Would this same standard meet the reasonable certainty of no harm standard? If not, what value(s) should be considered? In the discussion paper, CVM outlines two potential human health thresholds:

    • Human health threshold for enteric illness
    • Human health threshold for systemic illness

    These human health impact thresholds focus on the incremental effects on existing enteric illness or systemic illness in humans as a consequence of the causative bacteria being resistant to the antimicrobial drug the affected persons are expected to receive.

    CVM would like to solicit comments on the two human health thresholds described and suggestions for the levels at which they should be set.

  3. The discussion paper outlines an approach to the establishment of human health thresholds that focuses on enteric illness and systemic illness in humans. This approach recommends considering the impacts on enteric and systemic illness separately. An alternative to this approach would be to combine the human health impacts for enteric and systemic illness together using comparative weighting, and then have only one human health threshold.

    CVM would like comments on this alternative approach.

  4. What other approaches should be considered for establishing human health thresholds?
  5. Other comments
Session 4: Use of Risk Model to Establish Resistance Thresholds
  1. What are the strengths and limitations of the approach to establishing thresholds outlined in the CVM discussion document?
  2. According to the approach outlined in the CVM discussion document, resistance thresholds are derived using an epidemiology-based model.  In addition, the CVM document indicates that the NARMS program would be integral to monitoring resistance changes relative to the resistance thresholds.  Based on the model described, it is conceivable that derived resistance thresholds could be so low as to be below the limits of detection of the current NARMS program.  How should this situation be addressed?
  3. The outlined approach to the establishment of resistance thresholds has multiple complexities. CVM recognizes that there may be risk based methods to establish thresholds other than the approach outlined in this paper. What are alternatives to the proposed approach to establish resistance thresholds that CVM should consider?
  4. When an antimicrobial drug will be approved for use in multiple food animal species, it may be possible to divide the resistance threshold among the food animal commodity groups according to the individual commodity group’s contribution to all enteric disease.  Would this be a viable approach?
  5. How should resistance thresholds be updated after approval to take account of new information?  What criteria should trigger a reassessment of a current resistance threshold or lack of resistance threshold?
  6. Other comments