FDA Overview of

Antibiotic Regulatory Activities

Craig A. Lewis, DVM, MPH, DACVPM

Center for Veterinary Medicine (CVM)

U.S. Food and Drug Administration (FDA)

Presented to

NIAA 2014 Annual Conference

Antibiotics CouncilApril 1, 2014 1

Background

FDA’s ongoing strategy

Guidance for industry (GFI) #209

Draft guidance for industry (GFI) #213

Veterinary Feed Directives

Next Steps

Finalizing VFD Rule

Monitoring Progress

Topics

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 do not mean

that steps can’t be identified to mitigate risk.

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.

While debate continues, identify measures that

address public health concern and that continue to

assure animal health needs are met.

Remaining Concerns

A process is in place, with implementation of GFI 152 in

2003, that now evaluates the safety of antimicrobial new

animal drugs with regard to their microbiological effects on

bacteria of human health concern.

However, concerns remain about products that pre-date

current assessment process.

Focus of recent efforts is on taking steps to assure that

existing antibiotics (including those that predate 2003

assessment process) are used as judiciously as possible.

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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Published December 2013

Provides more detailed guidance on

implementation of key principles in Guidance 209

Definition of “medically important”

Process for updating product labels

Data required to obtain approval of new uses

Proposed implementation timeline

Guidance 213: Overview

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Guidance 213: Medical Importance

Proposed definition of medically important: those

drugs currently listed in GFI #152, Appendix A

regardless of their ranking

GFI #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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Guidance 213: Affected Drugs

Medically important antimicrobials

Administered in feed/water

Approved for production uses

Available OTC

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Guidance 213: Affected Drugs

7 Classes (with some examples):

Aminoglycosides (streptomycin, spectinomycin)

Lincosamides (lincomycin)

Macrolides (tylosin, erythromycin)

Penicillins (penicillin G procaine)

Streptogramins (virginiamycin)

Sulfonamides (sulfamethazine)

Tetracyclines (chlortetracycline, oxytetracycline)

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Guidance 213: New Uses

Potential new therapeutic uses

Therapeutic = treatment, control, prevention

Includes data required to obtain approval of new uses

Any new uses are expected to:

demonstrate therapeutic effectiveness

have defined dosing duration

include veterinary oversight

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Guidance 213: Timeline (3 months)

Requested notification from drug sponsors as to their

intentions within 3 months (by March 12, 2014)

FDA has received responses from all of the sponsors

affected by this guidance and is very encouraged by the

positive response.

The number of affected sponsors is 26.

25 sponsors confirmed their intent to engage in Guidance #213.

These 25 sponsors hold 99.6 percent of the applications affected

by Guidance #213.

These applications represent 99.95 percent of the total sales of

products affected by Guidance #213, based on 2011 data.14

Guidance 213: Timeline (3 years)

Target for implementing changes to use conditions of

affected products within 3 years (by December 12, 2016)

FDA is confident that these changes can be completed within the

three-year implementation period.

Veterinary Feed Directive (VFD) streamlining

To facilitate transition to increased veterinary oversight of

medicated feeds, FDA is also updating the VFD regulation.

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:

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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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.

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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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Updating the 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 19

Proposed VFD Rule: Major Provisions

Replace the explicit “veterinarian-client-patient relationship”

(VCPR) provision with the requirement that veterinarians

ordering the use of VFD drugs must do so “in compliance

with all applicable veterinary licensing and practice

requirements”

Revise the definition of Category II to eliminate the

automatic classification of VFD drugs into Category II.

Reduce the recording keeping burden for VFD drugs from

2 years to 1 year.

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Proposed VFD Rule: Example

Current process

Requires VFD orders be written for a specific amount of

medicated feed for specifically identified animals.

Proposed change

Allows veterinarians to be this specific, but also

provides the flexibility for veterinarians to issue a

broader "standing order"

For up to 6 months

Limited by approximate number of animals specified on the

VFD

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Guidance #213: Next Steps

Finalize VFD rule

Proposed rule published with final GFI #213

90-day public comment period (closed 3-12-2014)

Monitoring Progress of Guidance #213

Notifying Public

Assessing Impacts

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Notifying the Public of Progress

Listing all antimicrobial products and sponsors affected by

GFI #213

Publishing summary indicating the level of engagement of

affected drug sponsors following the 3-month notification

period indicated in the guidance

Notifying the public of completed changes to affected

products through publication of approval of supplemental

new animal drug applications

Evaluating the rate of adoption of the recommended

changes at the end of 3 years

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Assessing Impacts of Strategy

Monitoring trends in antimicrobial resistance among

foodborne bacteria from humans, retail meats, and animals

through the NARMS program.

Enhancing data FDA currently collects on the sales and

distribution of antimicrobial drugs intended for use in food-

producing animals.

Collaborating with other agencies, including USDA and the

CDC, to explore approaches for enhancing current data

collection efforts in order to measure the effectiveness of

the strategy.

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A Collaborative Approach

FDA believes that a collaborative approach is the

fastest way to implement the changes outlined in

Guidance #213.

We have worked with stakeholders, including

animal pharmaceutical companies, to encourage

their cooperation on this important public health

issue, and we are confident in their support.

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The Role of Animal Producers and

Veterinarians

Once drug companies voluntarily make these changes,

animal producers and veterinarians can no longer use

these products for production purposes, and therapeutic

use of these products would require veterinary oversight.

By law, drugs administered through feed must be used

according to the approved labeling.

In addition, the extralabel use of approved drugs in animals

by or on the lawful order of licensed veterinarians is limited

to situations where the health of an animal is threatened or

suffering or death may result from failure to treat.

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Judicious Prevention Use

A veterinarian practicing judicious use principles would

consider relevant factors to determine:

the risk of a specific bacterial disease,

whether it would be appropriate in a particular situation to use

medically important antimicrobials for prevention purposes.

For example, the veterinarian would consider:

the way the drug acts against the particular bacteria in question,

whether it can effectively reach the site of infection,

how long the drug maintains effective levels at the site of infection.

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Judicious Prevention Use

Other important factors veterinarians consider

when determining whether a particular drug is

appropriate for preventive use include whether:

1. There is evidence that the drug will be effective in treating the

particular disease.

2. Such preventive use is consistent with accepted veterinary

practice.

3. The use is intended to address particular bacteria.

4. The use is appropriately targeted to animals at risk of developing a

specific disease.

5. There are no reasonable alternatives for intervention. 28

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/u

cm042896.htm

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Thank You

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