FDA Overview of Antibiotic Regulatory Activities (Guidance 213, VFD, antibiotic use data collection) - Craig A. Lewis, DVM MPH DACVPM, U.S. Food and Drug Administration, from the 2014 NIAA Annual Conference titled 'The Precautionary Principle: How Agriculture Will Thrive', March 31 - April 2, 2014, Omaha, NE, USA. More presentations at http://www.trufflemedia.com/agmedia/conference/2014_niaa_how_animal_agriculture_will_thrive

1. 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 Council
April 1, 2014 1

2.  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 Draft guidance for industry (GFI) #213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

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 do not mean
that steps can’t be identified to mitigate risk.

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.
 While debate continues, identify measures that
address public health concern and that continue to
assure animal health needs are met.

5. 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.

6. 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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7. 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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8. 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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9.  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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10. 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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11. Guidance 213: Affected Drugs
 Medically important antimicrobials
 Administered in feed/water
 Approved for production uses
 Available OTC
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12. 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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13. 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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14. 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.
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15. 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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16. 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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17. 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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18. 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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19. 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
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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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27. 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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28. 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.
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29. 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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30. Thank You
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