[Federal Register Volume 65, Number 251 (Friday, December 29, 2000)]
[Pages 83070-83071]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-33215]



Food and Drug Administration

[Docket No. 00D-1677]

Discussion Paper: An Approach for Establishing Thresholds in 
Association With the Use of Antimicrobial Drugs in Food-Producing 
Animals; Availability

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.


SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a discussion paper entitled ``An Approach for 
Establishing Thresholds in Association With the Use of Antimicrobial 
Drugs in Food-Producing Animals (discussion paper).'' This discussion 
paper reflects the Center for Veterinary Medicine's (CVM's) current 
thinking on one concept for establishing resistance thresholds for 
antimicrobial drugs used in food-producing animals. The concept will be 
presented for discussion at a public meeting on January 22 to 24, 2001. 
CVM wants to receive comment on scientific and policy issues regarding 
this concept, as well as suggestions for alternative approaches.

DATES: Submit written comments on this discussion paper by April 9, 

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.
    See the SUPPLEMENTARY INFORMATION section for electronic access to 
the discussion paper. Persons without Internet access may submit 
written requests for single copies of this discussion paper to the 
Communications Staff (HFV-12), Center for Veterinary Medicine, Food and 
Drug Administration, 7500 Standish Pl., Rockville, MD 20855. Send one 
self-addressed adhesive label to assist that office in processing your 

FOR FURTHER INFORMATION CONTACT: For general inquiries: Sharon R. 
Thompson, Center for Veterinary Medicine (HFV-3), Food and Drug 
Administration, 7519 Standish Pl., Rockville, MD 20855, 301-827-4514, 
e-mail at sthompso@cvm.fda.gov.
    For technical inquiries: 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.


I. Background

    In the Federal Register of January 6, 1999 (64 FR 887), FDA 
announced the availability of a discussion paper entitled ``A Proposed 
Framework for Evaluating and Assuring the Human Safety of the Microbial 
Effects of Antimicrobial Drugs Intended for Use in Food-Producing 
Animals'' (the Framework Document). FDA made the Framework Document 
available to the public to initiate discussions with the scientific 
community and other interested parties on the agency's thinking about 
appropriate underlying concepts to be used to develop new policy for 
evaluating and ensuring that antimicrobial drug use in food-producing 
animals is safe for the public health. The Framework Document discussed 
several strategies for addressing concerns regarding the development of 
antimicrobial drug resistance associated with the use of antimicrobial 
drugs in food-producing animals. These strategies covered both 
preapproval and postapproval approaches and included: (1) Revision of 
the preapproval safety assessment for antimicrobial resistance for new 
animal drug applications to consider all uses of antimicrobial drugs in 
food-producing animals, (2) categorization of antimicrobial drugs based 
upon the importance of the drug for human medicine and upon which 
preapproval and postapproval requirements would be based, (3) 
postapproval monitoring of the development of antimicrobial drug 
resistance, and (4) elaboration of resistance and monitoring 
    The Framework Document discussed the concept of two thresholds, the 
resistance threshold and the monitoring threshold, that would be 
established prior to the approval of an antimicrobial new animal drug 
for use in food-producing animals to ensure that food products derived 
from the animal species treated with the drug are safe for consumers. 
The resistance threshold would be established in humans to represent 
the upper limit of resistant bacteria that can be transferred from 
animals to consumers. The Framework Document discussed the possibility 
of establishing resistance thresholds based on human data, animal data, 
or both.
    The Framework Document noted that monitoring thresholds also would 
be established to guide the postapproval monitoring of resistance 
development in animals. According to the Framework Document, a 
monitoring threshold would need to be determined for each antimicrobial 
drug prior to approval, and the threshold could vary depending on the 
human or animal pathogen of concern. Monitoring thresholds would be 
established in animals so that they would serve as an early warning 
system, signaling when loss of susceptibility or resistance prevalence 
is approaching the resistance threshold.
    If a monitoring threshold were reached, the drug sponsor could 
implement mitigation actions to address the loss of susceptibility or 
the increasing resistance trend. According to the concepts described in 
the Framework Document, if mitigation actions were found to be 
unsuccessful, and resistance levels exceeded the resistance threshold, 
withdrawal of the approval of the drug for the use(s) of concern would 
be warranted.
    The discussion paper, which is the subject of this notice of 
availability, further describes an approach for establishing thresholds 
intended to limit the emergence and spread of antimicrobial resistance 
in human pathogens attributed to antimicrobial drug use in food-
producing animals. The discussion paper attempts to describe the 
possible complexities of this approach to establishing thresholds in 
order to encourage discussion before, during, and after the January 
public meeting mentioned above. A notice of the public meeting was 
announced in the Federal Register of September 26, 2000 (65 FR 57820).
    The discussion paper discusses the use of two types of thresholds, 
a human health threshold and a resistance-in-animals threshold. The 
human health threshold represents the level at which there is no longer 
a reasonable certainty of no harm to human health associated

[[Page 83071]]

with antimicrobial resistance development as a consequence of 
antimicrobial drug use in food-producing animals. The resistance-in-
animals threshold represents the upper limit of acceptable levels of 
antimicrobial resistance in a food-producing animal species. This 
resistance threshold is derived through a risk assessment model that 
builds a link between the human health threshold and the resistance 
levels in animals. Therefore, exceeding the resistance threshold would 
be considered an unacceptable human health risk.

II. Comments

    This discussion paper is being distributed at this time for 
consideration by the public in anticipation of the January 22 to 24, 
2001, public meeting. Interested persons may submit to the Dockets 
Management Branch (address above) written comments regarding this 
discussion paper by April 9, 2001. Two copies of any comments are to be 
submitted, except that an individual may submit one copy. Comments are 
to be identified with the docket number found in brackets in the 
heading of this document. A copy of the docket including transcript and 
comments may be seen in the Dockets Management Branch between 9 a.m. 
and 4 p.m., Monday through Friday.

III. Electronic Access

    Copies of the discussion paper may be obtained on the Internet from 
the CVM home page at 

    Dated: December 21, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-33215 Filed 12-26-00; 11:47 am]