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

Background FDA’s ongoing strategy

Guidance for industry (GFI) #209 Draft guidance for industry (GFI) #213 Veterinary Feed Directives

Other AR-related activities NARMS Antimicrobial sales/use data

Topics

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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

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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

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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)

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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

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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

2010 – initiated “judicious use” effort with issuance of draft guidance 209

2012 – prohibited certain extralabel uses of cephalosporins

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Judicious Use of Antimicrobials

Guidance 209 – ‘‘The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals’’ Published as draft in June 2010

Finalized April 2012

Describes overall policy direction

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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)

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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

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Draft Guidance 213: Overview

Published April 2012

Provides more detailed guidance on implementation of key principles in Guidance 209

Definition of medically important

Process for updating product labelsData required to obtain approval of new uses

Proposed implementation timeline

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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

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Draft Guidance 213: Affected Drugs

Medically important antimicrobials

Administered in feed/water

Approved for production uses

Available OTC

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Draft Guidance 213: Affected Drugs

Examples include: Aminoglycosides

Streptomycin (water), Spectinomycin (water) Lincosamides

Lincomycin Macrolides

Tylosin, Erythromycin Penicillins

Penicillin G procaine Streptogramins

Virginiamycin Sulfonamides

Sulfamethazine Tetracyclines

Chlortetracycline, oxytetracycline

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Draft Guidance 213: New Uses

Stakeholder input revealed concerns that removing production uses might negatively impact animal health

Potential new therapeutic uses Therapeutic = treatment, control, prevention Includes data required to obtain approval of new uses Any new uses expected to:

Demonstrate therapeutic effectiveness Have defined dosing duration Include veterinary oversight

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Draft Guidance 213: Timeline

Implementation timeframe 3 months after finalization of Guidance 213

Hear from drug sponsors as to their intentions

3 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

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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

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Veterinary Oversight

Primary objective is to include veterinarian in decision-making processDoes not require direct veterinarian involvement

in drug administration

Practically, this means changing marketing status from OTC to Rx or VFD

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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

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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

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Updating VFD Process

Changes intended to make process more efficient

Critically evaluated all current requirements Information required on VFD form

Transmitting VFD

Recordkeeping requirements

Specificity of order

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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

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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

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Other AR-related activities

Enhancing antimicrobial resistance dataNARMS

Enhancing antimicrobial sales/use dataADUFA 1052012 ANPRM

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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

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NARMS: Examining sampling strategies

5 on-farm pilot studies initiated in September 2011 Explore feasibility of a pre-

harvest (live animal) sampling approach for NARMS

New slaughter sampling initiated in March 2013 Worked with FSIS to acquire

intestinal samples at slaughter

Goal is a representative and sustainable animal sampling scheme

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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 food-producing animals

Provides measure of total weight of antimicrobials entering livestock distribution channels

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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

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Enhancing Antimicrobial Sales/Use Data

Advance notice of proposed rulemaking (ANPRM) published July 27, 2012

Public input requested on: Enhancements to existing sales/distribution data Format of FDA’s annual summary Other sources of information on use

Comment period extended Closed November 26, 2012

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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

Enhancing Antimicrobial Sales/Use Data

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Related CVM Websites

Judicious Use of Antimicrobials: http://

www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/JudiciousUseofAntimicrobials/default.htm

NARMS http://

www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/default.htm

ADUFA 105 Reports: http://

www.fda.gov/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/ucm042896.htm

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Thank You

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