This document summarizes the FDA's ongoing efforts to address antimicrobial resistance related to food-producing animals. It discusses the FDA's strategy of issuing guidance documents like GFI #209 and #213 to promote the judicious use of medically important antimicrobials in animals. These guidances aim to limit antimicrobial use to therapeutic purposes and increase veterinary oversight through mechanisms like veterinary feed directives. The document also outlines the FDA's activities to enhance antimicrobial resistance monitoring through NARMS and collect antimicrobial sales and use data to inform policies.

1. FDA-CVM Activities Regarding
Antimicrobial Resistance and
Food-producing Animals
Bridging the Gap
Between Animal Health and Human Health
November 13, 2013
Craig A. Lewis, DVM, MPH, DACVPM
Veterinary Medical Officer
Center for Veterinary Medicine (CVM)
U.S. Food and Drug Administration (FDA)
1

2. Topics

Background

FDA‟s ongoing strategy
 Guidance
 Draft
guidance for industry (GFI) #213
 Veterinary

for industry (GFI) #209
Feed Directives
Other AR-related activities
 NARMS
 Antimicrobial
sales/use data
2

3. Antimicrobial Resistance – In Perspective

Complex, multi-factorial issue


Acquired vs. naturally occurring
Use as a driver of resistance

All uses (human, animal, horticultural, other) are part of the picture

Gaps in our understanding of the issue remain – the
science continues to evolve

But, these complexities and uncertainties don‟t
mean that steps can‟t be identified to mitigate risk
3

4. Antibiotic Use in Animal Agriculture

Has been the subject of scientific and policy debate for
decades

Consumers, public health advocates, Congress, and others
continue to be concerned about public health impacts

Rather than continue debate, identify measures that
address public health concern and that continue to assure
animal health needs are met
4

5. FDA Measures to Address AR Risks

Since late 1980‟s – All “new” antibiotics have been
approved as Rx or VFD

1996 – National Antimicrobial Resistance Monitoring
System (NARMS) established

1997 – Extralabel use of fluoroquinolones and
glycopeptides prohibited

2003 – FDA established framework for assessing
antimicrobial resistance risks as part of drug approval
(Guidance 152)
5

6. Remaining Concerns

Although a process is in place (with implementation of GFI
152 in 2003) to provide assurance that new antibiotic
products are safe

Concerns remain about products that pre-date current
assessment process
6

7. Focus of Recent Activities

Steps to assure that existing antibiotics (including those
that predate 2003 Guidance 152 assessment process) are
used as judiciously as possible

These include:
 2005
– withdrawal of enrofloxacin in poultry
– initiated “judicious use” effort with issuance of
draft guidance 209
 2010
– prohibited certain extralabel uses of
cephalosporins
 2012
7

8. Judicious Use of Antimicrobials

Guidance 209 – „„The Judicious Use of Medically
Important Antimicrobial Drugs in Food-Producing
Animals‟‟
 Published
 Finalized
as draft in June 2010
April 2012
 Describes
overall policy direction
8

9. Judicious Use: Guidance 209

Focus is on initiating steps to assure that
medically important antimicrobial drugs are used
as judiciously as possible

Antimicrobials must continue to be available to
combat disease in animals
 including

treatment, control, and prevention
Goal: preserve availability of effective drugs (for
both humans and animals)
9

10. Judicious Use: Guidance 209

Two key principles outlined in Guidance 209:
1.
Limit use of medically important antimicrobial
drugs to those uses considered necessary for
assuring animal health (i.e., therapeutic
purposes)
2.
Increase veterinary involvement/consultation
10

11. Draft Guidance 213: Overview

Published April 2012

Provides more detailed guidance on
implementation of key principles in Guidance 209
 Definition
 Process
 Data
of medically important
for updating product labels
required to obtain approval of new uses
 Proposed
implementation timeline
11

12. Draft Guidance 213: Medical Importance

Proposed definition of medically important
 Those
drugs currently listed in Appendix A of Guidance
152 (regardless of their ranking)

Guidance 152 provides guidance on evaluating the potential
effects of antimicrobial new animal drugs on non-target bacteria
as part of the new animal drug application process

Appendix A describes a process for ranking antimicrobial drugs
with regard to their relative importance in human medicine
12

13. Draft Guidance 213: Affected Drugs

Medically important antimicrobials

Administered in feed/water

Approved for production uses

Available OTC
13

14. Draft Guidance 213: Affected Drugs

Examples include:

Aminoglycosides


Lincosamides


Virginiamycin
Sulfonamides


Penicillin G procaine
Streptogramins


Tylosin, Erythromycin
Penicillins


Lincomycin
Macrolides


Streptomycin (water), Spectinomycin (water)
Sulfamethazine
Tetracyclines

Chlortetracycline, oxytetracycline
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15. Draft Guidance 213: New Uses

Stakeholder input revealed concerns that
removing production uses might negatively impact
animal health

Potential new therapeutic uses
 Therapeutic
 Includes
 Any
= treatment, control, prevention
data required to obtain approval of new uses
new uses expected to:

Demonstrate therapeutic effectiveness

Have defined dosing duration

Include veterinary oversight
15

16. Draft Guidance 213: Timeline

Implementation timeframe
3
months after finalization of Guidance 213

3
Hear from drug sponsors as to their intentions
years after finalization of Guidance 213

Target for implementing changes to use conditions of affected products
 VFD

streamlining
Intent is to implement revised VFD regulation within 3-year timeframe,
but will adjust timeframe as necessary if VFD changes not yet in effect
16

17. Veterinary Oversight

One of two key principles described in
Guidance 209:
 Limit
the use of medically important
antimicrobial drugs to those uses that include
veterinary oversight/consultation
17

18. Veterinary Oversight

Primary objective is to include veterinarian
in decision-making process
 Does
not require direct veterinarian involvement
in drug administration

Practically, this means changing marketing
status from OTC to Rx or VFD
18

19. Veterinary Feed Directive

Existing framework for veterinary oversight of feed
use drugs is the veterinary feed directive (VFD)

In 1996 Congress passed Federal Law stating that
medicated feeds which require veterinary
oversight are designated VFDs

In 2001 FDA finalized regulations for distribution
and use of VFDs
19

20. Veterinary Feed Directive

The proposal to increase veterinary oversight of
feed use antimicrobials has raised concerns about
VFD requirements - including:

Limited experience with process

Administrative burden

Veterinary workforce limitations

Increased costs to producers

Impacts on feed industry
20

21. Updating VFD Process

Changes intended to make process more efficient

Critically evaluated all current requirements
 Information
required on VFD form
 Transmitting
VFD
 Recordkeeping
 Specificity
requirements
of order
21

22. Next Steps - GFI 213 & VFD

Comment period closed July 12, 2012
 Comments

have been analyzed
Publish final Guidance 213 and proposed VFD
regulation
 An
FDA priority for 2013
 Both
documents currently in clearance at OMB
 Final
Guidance 213 will “start clock”
 Proposed
VFD rule will be open for public comment
before revisions and publication of final rule
22

23. Public Meetings

Worked with USDA to plan series of listening
sessions
 Primary
focus on mechanisms for helping
assure access to vet services in remote or
under served locations
 In
Spring 2013 held meetings in 5 locations
identified by USDA
23

24. Other AR-related activities

Enhancing antimicrobial resistance data
 NARMS

Enhancing antimicrobial sales/use data
 ADUFA
 2012
105
ANPRM
24

25. Enhancing NARMS Program

Comments previously received from FDA‟s
Science Board included:
 Sampling
needs to be nationally representative
 Sampling
biases occur as processing plants are not
randomly selected
 On-farm
data are essential in understanding movement
of resistance from farm to fork
25

26. NARMS: Examining sampling strategies

5 on-farm pilot studies initiated
in September 2011


New slaughter sampling initiated
in March 2013


Explore feasibility of a preharvest (live animal) sampling
approach for NARMS
Worked with FSIS to acquire
intestinal samples at slaughter
Goal is a representative and
sustainable animal sampling
scheme
26

27. Antimicrobial Sales Data: ADUFA 105

ADUFA Section 105 introduced
as part of 2008 Animal Drug
User Fee Amendment
reauthorization

Requires FDA to collect and
publicly report annual
summaries of antimicrobial
sales intended for use in foodproducing animals

Provides measure of total
weight of antimicrobials entering
livestock distribution channels
27

28. Antimicrobial Sales Data: Limitations

Sales do not necessarily represent end-use



Complex distribution channels
Not all product ultimately used
No way to distinguish how much intended for individual
species or for a particular indication


Most approvals for multiple species/indications
Confidential business information (CBI) protection
requirements

Prevent publication of sales with less than 3 distinct sponsors
28

29. Enhancing Antimicrobial Sales/Use Data

Advance notice of proposed rulemaking (ANPRM)
published July 27, 2012

Public input requested on:


Format of FDA‟s annual summary


Enhancements to existing sales/distribution data
Other sources of information on use
Comment period extended

Closed November 26, 2012
29

30. Enhancing Antimicrobial Sales/Use Data

Enhancements to existing sales/distribution data


Developing rulemaking (e.g. requiring sponsor estimates of sales
by species)
Format of FDA‟s annual summary



Evaluating alternative formats that provide additional information
while protecting CBI
FR Notice published September 26, 2013 seeking public comments
on proposed additional tables
Other sources of information on use

Collaboration with USDA and CDC to collect on-farm antimicrobial
use data that can be linked to shifts in resistance patterns
30

31. Related CVM Websites

Judicious Use of Antimicrobials:


NARMS


http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance
/JudiciousUseofAntimicrobials/default.htm
http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance
/NationalAntimicrobialResistanceMonitoringSystem/default.htm
ADUFA 105 Reports:

http://www.fda.gov/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/u
cm042896.htm
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32. Thank You
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