#273 
 
Defining Durations of Use for Approved 
Medically Important Antimicrobial Drugs 
Fed to Food-Producing Animals 
 
Guidance for Industry 
 
Draft Guidance 
 
This guidance document is being distributed for comment purposes only. 
Submit comments on this draft guidance by the dated provided in the Federal Register notice 
announcing the availability of the draft guidance. Submit electronic comments to 
https://www.regulations.gov. Submit written comments to the Dockets Management Staff (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All 
comments should be identified with docket number FDA-2023-D-2925. 
For further information regarding this document, contact John M. Mussman, DVM, Center for 
Veterinary Medicine (HFV-133), Food and Drug Administration, 7500 Standish Place, Rockville 
MD 20855, 240-402-0589, email: john.mussman@fda.hhs.gov. 
Additional copies of this draft guidance document may be requested from the Policy and 
Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 
7500 Standish Place, Rockville MD 20855, and may be viewed on the Internet at 
https://www.fda.gov/animal-veterinary, https://www.fda.gov/regulatory-information/search-fda-
guidance-documents, or http://www.regulations.gov. 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
September 2023 
 
   Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
  Table of Contents 
I.  Introduction ....................................................................................................................... 1 
II.  Background ....................................................................................................................... 1 
III.  Scope................................................................................................................................... 3 
IV.  Objectives........................................................................................................................... 4 
A.  Appropriately Defining the Duration of Use ............................................................ 5 
B.  Providing Additional Information for the Veterinarian ......................................... 5 
V.  Voluntary Adoption of Judicious Use Principles ........................................................... 7 
VI.  Timelines for Implementing Changes ............................................................................. 7 
A.  Timeline for Sponsors Defining a Duration of Use on the Labeling ...................... 8 
B.  Timeline for Sponsors Choosing to Request Withdrawal of the Approval of      
an Indication or of an Entire Application .............................................................. 11 
VII.  Supplemental NADAs (Pioneer Drugs) ......................................................................... 11 
A.  Pioneer (NADA) Single-Ingredient and Fixed-Ratio Combination Type A 
Medicated Articles .................................................................................................... 12 
B.  Pioneer (NADA) Feed-Use Combinations .............................................................. 22 
C.  Proprietary Free-Choice Medicated Feed Labeling Maintained Under a       
VMF ........................................................................................................................... 25 
D.  Marketing Exclusivity Considerations .................................................................... 26 
VIII.  Supplemental ANADAs (Generic Drugs) ..................................................................... 27 
A.  Revising Conditions of Use through Conforming Labeling Changes .................. 28 
B.  Administrative Procedures and Submission Content ............................................ 28 
C.  Defining a Duration of Use if Approval of the RLNAD is Withdrawn ................ 29 
IX.  Voluntary Withdrawal of Approval of a Regimen or an Indication with an 
Undefined Duration of Use from an NADA or Voluntary Withdrawal of the     
Entire (A)NADA .............................................................................................................. 29 
A.  Withdrawing Approval of a Regimen or an Indication from an NADA ............. 30 
B.  Withdrawing Approval of an Entire Application .................................................. 31 
X.  Glossary ........................................................................................................................... 31 
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Defining Durations of Use for Approved Medically Important 
Antimicrobial Drugs Fed to Food-Producing Animals 
 
Draft Guidance for Industry 
 
This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
Administration (FDA or Agency) on this topic. It does not establish any rights for any person 
and is not binding on FDA or the public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations. To discuss an alternative approach, 
contact the FDA staff responsible for this guidance as listed on the title page. 
I.  Introduction 
This guidance is intended for sponsors of approved new animal drug applications (NADAs) and 
abbreviated new animal drug applications (ANADAs) containing antimicrobial drugs: (1) 
important to human medicine (medically important antimicrobial drugs), (2) for use in or on 
the medicated feed of food-producing animals, and (3) that are currently approved with one or 
more indications that have an undefined duration of use.  Medically important antimicrobial 
drugs and undefined duration of use are discussed further in section III. Scope of this guidance.  
The framework outlined in this guidance will facilitate voluntary changes to have all medically 
important antimicrobial new animal drugs administered in alignment with the principles of 
judicious use.1  Establishing appropriately defined durations of use to mitigate the development 
of antimicrobial resistance is consistent with previous and ongoing efforts by FDA to protect 
public health by promoting the judicious use of medically important antimicrobial drugs in 
animals.  This guidance provides specific recommendations on how sponsors may facilitate 
changes to the approved conditions of use of affected products in support of ongoing efforts to 
mitigate the development of antimicrobial resistance. 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
II.  Background 
On April 13, 2012, FDA issued Guidance for Industry (GFI) #209, The Judicious Use of 
Medically Important Antimicrobial Drugs in Food-Producing Animals.2  In GFI #209, FDA 
stated that the development of resistance to medically important antimicrobial drugs, and the 
 
1 See FDA CVM Webpage, Judicious Use of AntimicrobialsAntimicrobial Resistance, 
https://public4.pagefreezer.com/browse/FDA/21-11-2022T08:21/https://www.fda.gov/judicious-use-antimicrobials. 
2 https://www.fda.gov/media/79140/download 
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resulting loss of their effectiveness as antimicrobial therapies, poses a serious public health 
threat.  As part of addressing this issue, FDA recommended in GFI #209 the following two 
principles to help promote the appropriate or judicious use of medically important antimicrobial 
drugs in food-producing animals: 
(1)  Limit medically important antimicrobial drugs to uses in food-producing animals that 
are considered necessary for ensuring animal health (i.e., to treat, control, and prevent 
disease), and 
(2)  Limit medically important antimicrobial drug uses in food-producing animals to uses 
that include veterinary oversight or consultation. 
On December 12, 2013, FDA issued GFI #213, New Animal Drugs and New Animal Drug 
Combination Products Administered in or on Medicated Feed or Drinking Water of Food-
Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product Use 
Conditions with GFI #209.3  Based on recommendations in that final guidance, sponsors of 
medically important antimicrobial drugs approved for use in or on the feed or drinking water of 
food-producing animals voluntarily worked with FDA to accomplish withdrawal of approval of 
indications that were not considered necessary for ensuring animal health (i.e., production 
indications), and change of all remaining approved uses of such new animal drugs from over-the-
counter (OTC) to either veterinary feed directive (VFD) or prescription (Rx) marketing status, as 
applicable.  FDA, working in conjunction with sponsors of the affected animal drug products, 
successfully completed implementation of GFI #213 in January 2017.4  
On September 14, 2016, FDA announced that it intended to enter the next phase of its efforts to 
mitigate antimicrobial resistance by focusing on medically important antimicrobials used in 
animal feed or water that have at least one therapeutic indication without a defined duration of 
use.  These older products were approved prior to FDAs current understanding of the 
importance of including a defined duration as one of the principles of judicious use.  In a notice 
published in the Federal Register (81 FR 63187),5 the Agency requested public comment 
regarding the establishment of appropriately defined durations of use for therapeutic products 
affected by GFI #213 with no defined duration of use.  Feedback received in response to that 
request for comments was taken into consideration during development of this guidance.  
On September 14, 2018, FDA released a 5-year action plan for supporting antimicrobial 
stewardship in veterinary settings.6  This plan builds upon the important steps the FDA Center 
for Veterinary Medicine (CVM) has already taken to support the judicious use of antimicrobials 
 
3 https://www.fda.gov/media/83488/download 
4 https://wayback.archive-
it.org/7993/20190423131636/https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm535154.htm  
5 https://www.federalregister.gov/documents/2016/09/14/2016-21972/the-judicious-use-of-medically-important-
antimicrobial-drugs-in-food-producing-animals-establishing 
6 FDAs 5-year action plan is entitled Supporting Antimicrobial Stewardship in Veterinary Settings: Goals for 
Fiscal Years 2019-2023. (https://www.fda.gov/media/115776/download). 
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in food-producing animals,7 and is driven by the concept that medically important antimicrobial 
drugs should only be used in animals when necessary for the treatment, control, or prevention of 
specific diseases. Action item 1.1.2 included in this plan is to ensure that all medically 
important antimicrobial drugs used in the feed or drinking water of food-producing animals have 
an appropriately targeted duration of use.8 
Starting in 2019, CVM began offering multiple funding opportunities9 to support the conduct of 
studies that are intended to generate data to help establish appropriately defined durations of use 
for certain medically important antimicrobial drugs approved for use in the feed of food-
producing animals.  This funding was intended to provide publicly available data that may be 
used by sponsors of affected approved new animal drugs to help support revisions to the 
conditions of use for products consistent with the objectives outlined in this guidance.  When the 
studies are complete, CVM intends to make the final study reports and data available in a Public 
Master File, and they may be used as applicable to inform labeling changes discussed in this 
guidance. 
On January 11, 2021, FDA published and requested public comment on a concept paper titled 
Potential Approach for Defining Durations of Use for Medically Important Antimicrobial Drugs 
Intended for Use In or On Feed: A Concept Paper (86 FR 1979).10  The concept paper described 
a potential framework for how animal drug sponsors could voluntarily work with FDA to make 
changes to the approved conditions of use for certain medically important antimicrobial drugs 
(i.e., those described in section III. Scope of this guidance), to establish an appropriately defined 
duration of use for those indications that currently lack a defined duration of use.  FDA 
considered all information and public feedback received in response to the concept paper during 
development of this guidance.  
III.  Scope 
This guidance is applicable to all medically important antimicrobial drugs that are approved11 for 
use in or on medicated feed of food-producing animals that have one or more indications with 
undefined durations of use on currently approved labeling.  For purposes of this guidance, an 
undefined duration of use means that the labeling for the identified product includes no 
information regarding duration of feeding or otherwise does not provide an appropriately 
targeted duration of use.  For purposes of this guidance, an appropriately defined duration of 
use means that the information regarding duration of feeding on the labeling ensures that the 
drug is used only when animals need it and provides the veterinarian appropriate flexibility to 
 
7 https://www.fda.gov/animal-veterinary/safety-health/antimicrobial-resistance 
8 See Action 1.1.2 on page 7 of FDAs 5-year action plan. 
9 https://public4.pagefreezer.com/browse/FDA/29-01-2023T09:49/https://www.fda.gov/animal-veterinary/cvm-
updates/fda-announces-2020-funding-opportunity-help-define-durations-use-certain-medically-important 
10 See also https://www.fda.gov/animal-veterinary/cvm-updates/fda-seeks-public-comment-potential-approach-
defining-durations-use-certain-medically-important. 
11 Including products that are not currently marketed. 
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use the drug consistent with the labeling in a range of scenarios that may be encountered in 
practice.  The scope of this guidance is limited to those drugs that are approved for use in or on 
animal feed because all the approved uses of medically important antimicrobial drugs in other 
(non-feed) dosage forms already have appropriately defined durations of use.12  FDA has made 
public on its website a listing of all medically important antimicrobial drugs administered in the 
feed of food-producing animals that currently have one or more approved indications with an 
undefined duration of use.13  FDA intends for all drugs that appear in this listing, hereinafter 
referred to as affected products or affected applications, to be included within the scope of 
this guidance.  FDA refers to Appendix A of GFI #152 for FDAs determination of which 
antimicrobial drugs/drug classes are considered medically important for purposes of its 
strategy to promote the judicious use of antimicrobial drugs in animals.  The list of medically 
important antimicrobial drugs/drug classes in Appendix A is not static and FDA has previously 
stated its intent to periodically reassess this list consistent with contemporary science and current 
human clinical practices.14  Therefore, the antimicrobial products within the scope of this 
guidance may change in the future as FDA revises the list of antimicrobial drugs that are 
considered medically important. 
IV.  Objectives 
FDAs objective in issuing this guidance is to provide specific recommendations to animal drug 
sponsors on how to revise the product use conditions (e.g., dosage regimen, instructions for use) 
of affected products, as necessary, to better target when and for how long a drug may be used to 
effectively treat, control, or prevent the disease(s) for which the product is indicated.  Such 
revisions are intended to provide for the continued effective use of these products while 
minimizing the extent of antimicrobial drug exposure, thereby supporting efforts to mitigate the 
development of antimicrobial resistance.  Establishing appropriately defined durations of use for 
the affected applications supports the FDA's ongoing efforts to slow the development of 
antimicrobial resistance by fostering the judicious use of medically important antimicrobial 
drugs in animals.  
Revisions to product use conditions (as reflected through revisions to the approved labeling) 
generally should include appropriately defining the duration of use for the product and, where 
appropriate, providing additional information to facilitate the veterinarians oversight of the 
products feeding to animals in a manner consistent with the principles of judicious use.  As 
 
12 Although FDAs 5-year action plan for supporting antimicrobial stewardship included an action item calling for 
the Agency to develop a strategy for establishing appropriately defined durations of use for medically important 
antimicrobial drugs used in or on the feed or drinking water of food-producing animals, CVM has determined that 
all of the approved uses of medically important antimicrobial drugs used in drinking water already have 
appropriately defined durations of use. 
13 https://www.fda.gov/animal-veterinary/antimicrobial-resistance/list-approved-medically-important-antimicrobial-
drugs-administered-feed-food-producing-animals-lack  
14 See Action 1.3.1 on page 9 of FDAs 5-year action plan.  See also Table A1 of Appendix A in draft GFI #152, 
Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on 
Bacteria of Human Health Concern, (December 2022).  When final, this guidance will represent FDAs current 
thinking on this topic. 
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discussed in more detail in section VII. Supplemental NADAs (Pioneer Drugs) of this guidance, 
the recommendations in this guidance are not expected to impact any technical sections other 
than Labeling and Environmental Impact. 
A.  Appropriately Defining the Duration of Use 
For affected products that currently lack a defined duration of use for one or more 
indications, the labeling should be revised to include appropriate criteria regarding when 
to begin and end feeding of the antimicrobial drug.  As discussed in more detail in section 
VII. Supplemental NADAs (Pioneer Drugs) of this guidance, an appropriately defined 
duration of use should consist of the expected duration bounded by a maximum permitted 
duration.  
The expected duration of use is the duration to be ordered by the veterinarian in 
accordance with the labeled directions for use.  The expected duration should be defined 
in terms of evidence of disease in the group of animals (in the case of treatment or control 
indications) or the period during which animals are at risk for the disease (in the case of 
prevention and prevention-like indications), as determined by the veterinarian. 
The maximum permitted duration of use is the duration that cannot15 be exceeded for a 
single course of therapy ordered by a veterinarian.  The maximum permitted duration is 
not intended to be routinely ordered. It should:  
  provide the veterinarian appropriate flexibility to use the drug consistent with the 
labeling in a range of scenarios that may be encountered in practice,  
  be consistent with what is known about the risk factors, pathogenesis, and 
progression of the indicated disease, and  
  be defined in terms of maximum time that the drug may be used (e.g., days or 
weeks).  Depending on the disease, target species, and class, it may be more 
appropriate to define the maximum permitted duration of use in terms of 
maximum animal age or maximum animal body weight, rather than time. 
A sponsor should not use instructions such as feed until market weight to define the 
duration of use.  Likewise, sponsors should not use instructions to stop feeding by a 
certain age, when that age equals or exceeds the typical slaughter age of that species and 
class, to define the duration of use.  In addition, a slaughter withdrawal period on the 
labeling should not be used to define the duration of use. 
B.  Providing Additional Information for the Veterinarian 
These products are now VFD products requiring the oversight of a licensed veterinarian.  
Therefore, in addition to establishing defined durations as required conditions of use, it is 
 
15 Extralabel use of medicated feeds is prohibited.  See section 512(a)(4)(A) of the FD&C Act; 21 CFR 530.11(b).  
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appropriate to revise the approved product labeling to include additional information 
intended for the authorizing veterinarian to consider when writing a VFD.  Such 
information is expected to vary depending on the specific indication for use in question, 
including whether the indication is for disease treatment, control, or prevention.  Such 
information should appear in an Additional Recommendations section of the labeling 
and be presented in a manner that does not imply limits on the veterinarians ability to 
exercise professional judgement. 
For purposes of this guidance, the terms treatment, control, and prevention are defined as 
follows: 
Treatment:  The drug is administered only to animals diagnosed (based on clinical 
signs or other appropriate diagnostic methods) with the indicated disease. 
Relevant labeling information:  The veterinarians decision to use a medically 
important antimicrobial drug approved for treatment purposes, in a judicious manner, 
ordinarily includes consideration of factors relevant to: (1) diagnosing in the animals 
the bacterial disease indicated on the approved labeling, and (2) determining whether 
use of the drug in question to treat the disease is appropriate in a particular situation.  
The types of information provided on product labeling to assist veterinarians in 
deciding whether and how to use an antimicrobial drug indicated for disease 
treatment may include: 
  Information to support disease diagnosis 
  Clinical pharmacology information 
  Microbiology information  
  Clinical effectiveness information 
Control:  The drug is administered to a group of animals once a proportion16 of the 
animals in the group have been diagnosed (based on clinical signs or other 
appropriate diagnostic methods) with the indicated disease. 
Relevant labeling information:  The veterinarians decision to use a medically 
important antimicrobial drug approved for control purposes, in a judicious manner, 
ordinarily includes consideration of factors relevant to: (1) diagnosing the bacterial 
disease indicated on the approved labeling in a proportion of the animals in the group, 
and (2) determining whether use of the drug in question to control the disease is 
appropriate in a particular situation.  The types of information provided on product 
labeling to assist veterinarians in deciding whether and how to use an antimicrobial 
drug indicated for disease control may include: 
  Information to support disease diagnosis 
 
16 A percentage that is greater than 0% and less than 100%, unless otherwise specified on the labeling. 
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  Epidemiologic information regarding the indicated disease 
  Clinical pharmacology information 
  Microbiology information 
  Clinical effectiveness information 
Prevention:  The drug is administered to a group of animals, none of which have 
been diagnosed with the indicated disease, when transmission of existing 
undiagnosed infections or the introduction of pathogens is anticipated based on 
history, clinical judgment, or epidemiological knowledge. 
Relevant labeling information:  The veterinarians decision to use a medically 
important antimicrobial drug approved for prevention purposes (including prevention-
like purposes such as reduction of disease incidence) in a judicious manner ordinarily 
includes consideration of factors relevant to: (1) determining the risk that the disease 
indicated on the approved labeling will occur in the animals, and (2) determining 
whether use of the drug in question to prevent the disease is appropriate in a 
particular situation.  The types of information provided on product labeling to assist 
veterinarians in deciding whether and how to use an antimicrobial drug indicated for 
disease prevention may include: 
  Environmental risk factors for the indicated disease (e.g., related to 
temperature, ventilation, animal transportation conditions)  
  Host risk factors for the indicated disease (e.g., related to age, production 
class or production stage, nutrition, breed or genetics, stressors, immune 
status)  
  Epidemiologic information regarding the indicated disease 
  Clinical pharmacology information 
  Microbiology information 
  Clinical effectiveness information 
V.  Voluntary Adoption of Judicious Use Principles 
Based on the successful implementation of the recommendations made in GFIs #209 and #213, 
FDA believes the approach outlined in this guidance is the most effective and efficient means of 
furthering the goal of judicious use of medically important antimicrobial drugs in animals.  CVM 
will work with affected drug sponsors who opt to revise the use conditions for those product 
indications that are currently approved with an undefined duration of use. 
VI.  Timelines for Implementing Changes 
In order to ensure progress under the cooperative framework outlined in this guidance, FDA will 
monitor progress to assess whether changes are being adopted along the timelines discussed 
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below. If, after three years as discussed below, FDA determines that adequate progress has not 
been made, FDA will consider whether further action under the existing provisions of the FD&C 
Act may be appropriate. 
A.  Timeline for Sponsors Defining a Duration of Use on the Labeling 
As discussed in section VII.A.1. Submit Proposals with Justification to CVM for Review 
of this guidance, the following should be addressed to establish appropriately defined 
durations of use on applicable pioneer17 products: (1) labeling statements describing the 
expected duration of use (see section VII.A.1.a. Defining the Expected Duration of Use); 
and (2) a labeling statement establishing the maximum permitted duration of use, 
supported with a scientific justification (e.g., white paper) based on available information 
(e.g., peer-reviewed literature) about the disease (see section VII.A.1.b. Defining the 
Maximum Permitted Duration of Use).  In addition, pioneer sponsors should propose any 
additional information for the veterinarian to consider and any appropriate antimicrobial 
resistance mitigation statements for inclusion on the labeling. 
The timeframes described in this guidance are intended to fully implement the 
recommendations in this guidance within as short a time as possible following 
finalization of this guidance.  FDA anticipates that sponsors of affected products should 
be able to have revised labeling approved that incorporates the changes discussed in this 
guidance within 3 years from the date of publication of the final version of this guidance.    
To achieve this goal, sponsors should submit the various submissions for their affected 
applications in a timely manner as outlined below. 
1.  Step 1 (Proposal and Support for Intended Labeling Revisions for Affected 
NADA Type A Medicated Articles and Non-Animal Drug Availability Act 
(ADAA) Feed-Use Combinations) 
Sponsors of affected NADA Type A medicated articles (including fixed-ratio 
combination Type A medicated articles)18 and NADA non-ADAA19 feed-use 
combinations (for purposes of this guidance, these will be referred to as top-level 
applications) should submit proposals and information that would support the labeling 
changes described in this guidance.  Sponsors should submit these proposals in a 
STARS20 G submission (general correspondence submission) for CVM review.  
Sponsors may choose to coordinate with each other if they are interested in seeking 
 
17 NADA single-ingredient and fixed-ratio combination Type A medicated articles, and NADA feed-use 
combinations that are approved under section 512(d)(1)) of the FD&C Act. 
18 Type A medicated articles are defined in 21 CFR 558.3(b)(2). 
19 NADA, Animal Drug Availability Act (ADAA), and NADA non-ADAA feed-use combinations are discussed 
further in section VII.B Pioneer (NADA) Feed-Use Combinations of this guidance. 
20 STARS is CVMs Submission Tracking and Reporting System.  For information on electronic submission through 
eSubmitter, see https://www.fda.gov/animal-veterinary/development-approval-process/electronic-submissions. 
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approval for the same conditions of use across the same or similar indications.  CVM 
generally responds to G submissions within 180 days.  
For purposes of this guidance, a downstream application or file type is one that 
relies on and conforms to the conditions of use established for the application(s) that 
it references.  CVM is not able to review labeling supplements for downstream 
applications and files until the supplement for the referenced application has been 
received.  Sponsors of top-level NADAs who are unsure whether their application 
serves as a reference for one or more downstream applications or files are encouraged 
to contact CVMs Office of New Animal Drug Evaluation to confirm.  Of the 
applications affected by this guidance, ANADA Type A medicated articles, NADA 
ADAA feed-use combinations, and ANADA feed-use combinations are downstream 
applications.  Veterinary Master Files (VMFs) are a type of downstream file that 
maintain labeling for reference in an application.  Step 1 does not apply to 
downstream applications or VMFs. 
Sponsors of top-level applications should submit their proposals in a G submission as 
soon as practicable within the timeframe indicated below: 
  Top-level NADAs that serve as references for one or more downstream 
applications or files:  submit the G submission no later than 3 months 
following finalization of this guidance. 
  Top-level NADAs that do not serve as references for any downstream 
applications or files:  submit the G submission no later than 1 year following 
finalization of this guidance. 
If desired, sponsors may contact CVM to discuss their plans informally or formally 
(e.g., in a presubmission conference) before submitting their G submission. Whether 
or not such discussions are held, sponsors of top-level NADAs should cooperate with 
the above submission timeframes, to facilitate the submissions described in Step 2 
below being submitted and reviewed in a timely manner.  
When review of the G submission is complete, CVM will issue a letter to the sponsor.  
CVM anticipates that only in some exceptionally complex cases will more than 180 
days be needed. 
2.  Step 2 (Labeling Supplement Submission and Approval/Project Completion 
for all Affected Applications) 
As soon as possible after CVM has issued a letter regarding the G submission (for 
top-level NADAs), or after they are contacted by CVM (for downstream applications 
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and files), sponsors should submit non-fee21 supplemental applications (labeling 
supplements) to request approval of the revised conditions of use and associated 
labeling components for each affected application. 
Because of the way downstream applications and files are structured, sponsors will 
face constraints on the sequencing of certain submissions.  Those structures are:  
  ANADA Type A medicated articles, ANADA feed-use combinations that 
reference an NADA non-ADAA feed-use combination, NADA ADAA feed-
use combinations, and Veterinary Master Files (VMFs) rely directly on the 
submission and review of a top-level NADA. 
  ANADA feed-use combinations that reference an NADA ADAA feed-use 
combination rely on the submission and review of a downstream application, 
which itself relied on previous submission and review of a top-level NADA. 
  Approvals for use of proprietary free-choice medicated feeds based on 
VMFs22 under the application for the source Type A medicated article rely on 
submission and review of revised labeling submitted to the VMFs. 
Due to the inherent complexity of interactions between top-level and downstream 
applications, CVM does not intend to synchronize approval of any of these 
supplements. However, CVM will work with sponsors as requested to determine the 
appropriate submission timing for specific labeling supplements based on: (1) 
expected workload of CVM and the sponsor, (2) existence of any impacted 
combination or proprietary free-choice medicated feeds and generic products, and (3) 
whether sponsors wish to coordinate with each other to minimize the time that elapses 
between approval of labeling supplements for products with similar indications. 
CVM intends to notify sponsors of downstream applications and files within 
approximately 2 weeks of receiving the labeling supplement for the referenced 
application.  For each type of downstream application or file, sponsors should submit 
their labeling supplement as soon as practicable within the following timeframes: 
  ANADA Type A medicated articles:  submit supplement within 60 days of 
notification of submission of the supplement for the reference listed new 
animal drug (RLNAD) Type A medicated article. 
 
21 Supplemental animal drug applications that do not require safety or effectiveness data do not incur fees under the 
Animal Drug User Fee Act (ADUFA) program.  Supplemental abbreviated applications for generic new animal 
drugs do not incur fees under the Animal Generic Drug User Fee Act (AGDUFA) program.  See sections 739, 740, 
and 741 of the FD&C Act. 
22 Discussed further in section VII.C. Proprietary Free-Choice Medicated Feed Labeling Maintained under a VMF 
of this guidance. 
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  NADA ADAA feed-use combinations:  submit supplement within 60 days of 
notification of submission of the supplement for the referenced NADA Type 
A medicated article.  
  ANADA feed-use combinations:  submit supplement within 60 days of 
notification of submission of the supplement for the RLNAD feed-use 
combination. 
  VMFs for proprietary free-choice medicated feeds:  submit revised labeling to 
the VMF within 60 days of notification of submission of the supplement for 
the referenced Type A medicated article.  
  NADA Type A medicated articles that are the source for proprietary free-
choice medicated feeds based on VMFs:  submit supplements to the NADA 
within 60 days of notification of submission of the revised labeling for the 
applicable VMFs. 
CVM will review these labeling supplements as sponsors submit them, according to 
established review timeframes.  NADA labeling supplements are assigned a 180-day 
review time, and ANADA labeling supplements are assigned a 270-day review 
time.23 
B.  Timeline for Sponsors Choosing to Request Withdrawal of the Approval of an 
Indication or of an Entire Application 
If sponsors intend to request withdrawal of the approval of an indication or an entire 
application, rather than define a duration of use, they should initiate the withdrawal 
process as described in section IX. Voluntary Withdrawal of Approval of a Regimen or an 
Indication with an Undefined Duration of Use or the Entire (A)NADA of this guidance 
within 1 year following finalization of this guidance.  CVM will review these requests as 
sponsors submit them, according to established review timeframes. 
VII.  Supplemental NADAs (Pioneer Drugs) 
This section describes the labeling changes that sponsors should request, how sponsors should 
propose and justify a maximum permitted duration of use for each affected indication, and the 
additional information sponsors should include in their labeling supplements.  In addition, this 
section describes administrative processes and marketing exclusivity considerations that should 
be taken into account.  Sponsors should use the process set forth in this section to provide 
appropriate information to support approval of their labeling supplement to establish a defined 
 
23 The Agency agreed to these review time goals for labeling supplements in the goals letters that accompanied the 
2018 reauthorization of the Animal Drug User Fee Act (ADUFA) 
(https://www.fda.gov/files/about%20fda/published/ADUFA-Reauthorization-Performance-Goals-and-Procedures-
%E2%80%93-FYs-2019-thru-2023.pdf) and the Animal Generic Drug User Fee Act (AGDUFA) 
(https://www.fda.gov/media/116328/download).  
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duration of use.  CVM also will consider other scientifically and legally appropriate alternatives 
that sponsors may propose. 
Because the affected indications are approved (safety and effectiveness have already been 
demonstrated) and the formulation is not expected to change, the establishment of appropriately 
defined durations of use is not expected to require review of safety, effectiveness, or chemistry, 
manufacturing, and controls information.  The steps recommended in this section are intended to 
apply to situations where the only substantive change to the approved application is defining 
previously undefined durations of use and no new indications or other substantive changes to the 
application are proposed.24  Making changes unrelated to defining previously undefined 
durations of use (for example, increasing or decreasing the dosage level, changing the product 
formulation, or making other substantive changes) is likely to require submission and CVM 
review of additional information or data.  The process recommended in this guidance also 
assumes that the currently-approved dosage level administered to target animals (for example, 
drug inclusion rate in feed or the amount of drug per head or per unit body weight) and the 
formulation of the product are not changing. 
A.  Pioneer (NADA) Single-Ingredient and Fixed-Ratio Combination Type A 
Medicated Articles 
For each indication with an undefined duration of use, the labeling should define the 
expected duration of use,25 define the maximum permitted duration of use,26 and when 
appropriate, provide additional information for the veterinarian to consider when ordering 
use of the drug,27 or information that would otherwise support the principles of judicious 
use and minimize the development and spread of antimicrobial resistance.28  
To help ensure efficient review of these labeling changes, sponsors should first submit 
proposed labeling changes in a G submission for CVM review and then submit a labeling 
supplement for approval, as described in this section. 
 
24 Sponsors choosing to propose new indications or make other substantive changes to the application (including 
changes to the labeling other than those described in this guidance) are encouraged to do so under a separate 
supplemental application that includes all applicable technical sections, following established procedures.  These 
procedures are described elsewhere and are beyond the scope of this guidance.  Sponsors choosing to pursue all 
labeling changes close in time (e.g., for a single future printing of labeling) may submit the subsequent supplemental 
application at any time, as early as the next day after the supplemental application for approval of revised labeling 
containing the defined duration of use is submitted. 
25 See section VII.A.1.a. Defining the Expected Duration of Use of this guidance. 
26 See section VII.A.1.b. Defining the Maximum Permitted Duration of Use of this guidance. 
27 See section VII.A.1.c. Providing Additional Information for the Veterinarian of this guidance. 
28 See section VII.A.1.d. Inclusion of Antimicrobial Resistance Mitigation Statements of this guidance. 
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1.  Submit Proposals with Justification to CVM for Review 
Sponsors should submit proposals with appropriate justification in a G submission 
before submitting the labeling supplement.  For each affected indication, proposals 
should include the expected duration of use, the maximum permitted duration of use 
(along with appropriate justification), any additional information for the veterinarian 
to consider, any appropriate antimicrobial resistance mitigation statements, and 
acknowledgement of intent to incorporate any additional labeling changes that may 
be needed, as discussed in this section. 
During Step 1, described in section VI.A. Timeline for Sponsors Defining a Duration 
of Use on the Labeling of this guidance, and before submitting a labeling supplement, 
sponsors of top-level NADAs should submit their proposals and supporting 
information to address the labeling changes discussed in this section in a G 
submission to CVMs Office of New Animal Drug Evaluation, Division of Food 
Animal Drugs (HFV-130) for review and comment.  A separate G submission should 
be prepared and submitted to each application file; however, sponsors may address all 
affected indications for a product in the same submission.  Sponsors may choose to 
request a presubmission conference to discuss proposals with CVM before submitting 
the G submission.  Sponsors are encouraged to include draft revised labeling for all 
affected components in the G submission to allow CVM to provide comments or 
concurrence in advance of the future labeling supplement.  If draft revised labeling is 
not included in the G submission, sponsors should provide a detailed text description 
of the proposed changes to the labeling. 
CVM considers each application individually.  CVM does not intend to consider 
proposals that may be submitted for one application when evaluating proposals 
submitted for another.  CVM is only able to communicate with sponsors regarding 
their own application files; however, CVM recognizes that the body of available 
information may support a range of durations that would be appropriate for use to 
treat, control, or prevent a given disease and that some sponsors may be interested in 
aligning the directions for use across products approved for the same or similar 
indications to the extent possible, even across products owned by different sponsors.  
CVM will not object if sponsors choose to coordinate among themselves to prepare 
and submit identical proposals and supporting information to their respective 
application files. 
Following review of the G submission, CVM will issue a letter to the sponsor.  The 
letter will indicate whether CVM generally agrees with the sponsors proposals and 
will provide additional comments as warranted.  CVM will work with sponsors 
formally and informally to review and comment on planned labeling revisions in an 
efficient manner. 
a.  Defining the Expected Duration of Use 
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The expected duration of use should be incorporated into the Directions29 section 
of the labeling.  For all affected indications across all affected products, the 
expected duration of use should be defined in the following terms, unless unique 
characteristics of a disease or other factors warrant a modified statement: (1) 
evidence of disease in the group (in the case of treatment or control indications), 
or (2) the period during which animals are at risk for the disease (in the case of 
prevention indications).  The Directions section of the labeling should be clear 
that the veterinarian is to determine the actual duration that the drug will be used 
in a specific group of animals.  
Therefore, one of the following statements (as applicable according to indication 
type and other considerations) should be included in the Directions section of the 
labeling for each affected indication.  The statements should be modified when 
necessary to incorporate and preserve any required directions for use (e.g., a 
minimum duration) that may appear on the currently approved labeling. 
  Treatment Indications:  
For most treatment indications, the following statement should be used:  
Feed only to animals that are diagnosed with the disease.  Begin feeding 
after the disease is diagnosed and continue until the animals no longer 
require this medication, as determined by the veterinarian.  
For indications that have a minimum duration of use required by the currently 
approved labeling, the following statement should be used:  
Feed only to animals that are diagnosed with the disease.  Begin feeding 
after the disease is diagnosed and continue for at least [describe minimum 
duration] until the animals no longer require this medication, as 
determined by the veterinarian.  
If warranted by unique aspects of the disease or drug (e.g., veterinary practice 
standards related to the disease or specifics related to the drugs mechanism of 
action), an alternative statement similar to the following may be used:  
Feed only to animals that are diagnosed with the disease.  Begin feeding 
after the disease is diagnosed and continue until [X] days after resolution 
of clinical signs, as determined by the veterinarian.  
 
29 Some currently approved product labeling may title this section differently (e.g., Directions for Use), or may not 
have a specific section title. 
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Sponsors who consider that such an alternative statement is applicable to their 
product indication should propose and justify the need for the statement, the 
specific wording, and the number of days that will appear in place of [X]. 
  Control Indications:  
For most control indications, the following statement should be used: 
Feed to a group of animals in which a proportion of the animals in the 
group has been diagnosed with the disease.  Begin feeding after the 
disease is diagnosed and continue until an acceptable degree of control has 
been reached in the group or the animals no longer require this 
medication, as determined by the veterinarian.  
For indications that have a minimum duration of use required by the currently 
approved labeling, the following statement should be used: 
Feed to a group of animals in which a proportion of the animals in the 
group has been diagnosed with the disease.  Begin feeding after the 
disease is diagnosed and continue for at least [describe minimum duration] 
until an acceptable degree of control has been reached in the group or the 
animals no longer require this medication, as determined by the 
veterinarian.  
If warranted by unique aspects of the disease or drug (e.g., veterinary practice 
standards related to the disease or specifics related to the drugs mechanism of 
action), an alternative statement similar to the following may be used: 
Feed to a group of animals in which a proportion of the animals in the 
group has been diagnosed with the disease.  Begin feeding after the 
disease is diagnosed and continue until [X] days after an acceptable degree 
of control has been reached in the group or until resolution of clinical 
signs, as determined by the veterinarian.  
Sponsors who consider that such an alternative statement is applicable to their 
product indication should propose and justify the need for the statement, the 
specific wording, and the number of days that will appear in place of [X]. 
  Prevention, Reduction in Incidence, and Similar Indications:  
For most prevention and similar indications, the following statement should 
be used: 
Feed to a group of animals that are at risk of developing the disease, but 
in which no animals have yet been diagnosed.  Begin feeding at the start 
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of the risk period and continue until animals are no longer at risk, as 
determined by the veterinarian.  
For indications that have a minimum duration of use required by the currently 
approved labeling, the following statement should be used: 
Feed to a group of animals that are at risk of developing the disease, but 
in which no animals have yet been diagnosed.  Begin feeding at the start 
of the risk period and continue for at least [describe minimum duration] 
until the animals are no longer at risk, as determined by the veterinarian.  
Antimicrobials approved for prevention and similar indications should not be 
labeled for use beyond when the animals are at risk of the disease. 
Sponsors should explain in their G submission how they intend to revise their 
labeling after considering the guidance above.  Sponsors do not need to provide 
any information to support the statements shown in this section except where 
noted above, or if a sponsor considers that none of the above statements are 
appropriate to a particular product indication.  Alternative statements may be 
acceptable if appropriately justified. 
b.  Defining the Maximum Permitted Duration of Use 
For each affected indication on the product labeling, the Directions section should 
state the maximum duration of use that is permitted for a single course of therapy 
ordered by a VFD.  The maximum permitted duration of use should appear in a 
Do not feed for more than X days or similar statement.  The maximum 
permitted duration of use should be appropriate for each indication and likely will 
be different for different indications.  The maximum permitted duration of use on 
the labeling should not be the duration veterinarians would routinely order, but 
instead should provide the veterinarian with adequate flexibility to use the drug 
consistent with the principles of judicious use in a range of legitimate 
circumstances or scenarios that might sometimes be encountered in the United 
States.  CVM anticipates that for most affected indications, it will be difficult to 
justify a proposed maximum permitted duration of use that approaches either the 
production lifespan of the target animal or the maximum VFD expiration date.30  
However, CVM acknowledges that for some affected indications, there likely are 
scenarios in which it will be necessary and consistent with the principles of 
judicious use to feed the drug for an extended period. 
Sponsors should propose the maximum permitted duration of use for each 
indication based on the relevant characteristics or dynamics of the indicated 
disease (e.g., disease risk periods, pathogenesis, progress, self-cure timeframes, 
 
30 If not otherwise specified in the approval, the VFD expiration date must not exceed 6 months after the date of 
issuance.  See 21 CFR 558.6(b)(3)(v). 
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expected outcomes, or other information as applicable).  Sponsors should support 
the proposal with a scientific justification (e.g., white paper) that is based on 
relevant available information such as peer-reviewed scientific literature, 
recognized standards of veterinary practice, a consensus of expert opinions, and 
other such information.  If appropriate and the sponsor chooses to do so, the 
justification may also draw on disease dynamics observations from previously 
conducted studies, or existing information relevant to the drug itself (e.g., 
mechanism of action, pharmacokinetics, or pharmacodynamics information that 
may help inform how long the drug may need to be used to be effective for the 
indicated disease in certain scenarios).  
The justification should be comprehensive, focused, balanced, and limit bias.  It 
should build the argument logically and present information that both supports 
and refutes (if such information exists) the proposed maximum permitted duration 
of use.  It is important that the justification include any information that is 
unfavorable as well as favorable to the proposal and explain why any apparently 
unfavorable information may not be applicable.  If there are major differences 
among sources, the justification should discuss possible reasons for those 
differences.  Finally, the justification should draw overall conclusions and explain 
the reasoning (with reference to the specific information used) behind those 
conclusions. 
If literature is used, the justification should include information on the database(s) 
searched, the keyword(s) and search string(s) used, and any limitations, such as 
date range(s) imposed.  Sponsors should provide complete copies of the papers 
referenced and a reference list with the justification.  If any information used for 
the justification is in a foreign language, an accurate and complete English 
translation of the information must31 also be included.  
Sponsors choosing to refer to previously conducted studies should only include a 
study report or summary of relevant observations, and not include raw data with 
the justification.  
c.  Providing Additional Information for the Veterinarian 
All Type A medicated article labels and representative (Blue Bird)32 Type B and 
Type C medicated feed33 labeling should include additional information for the 
veterinarian to consider when authorizing use of the drug.  This information 
should appear in an Additional Recommendations section.  Information in this 
section does not constitute required conditions of use.  This information is not 
 
31 See 21 CFR 514.1(a). 
32 See GFI #181, Blue Bird Medicated Feed Labels, (July 2019). 
33 Type B medicated feed and Type C medicated feed are defined in 21 CFR 558.3(b)(3) and (4), respectively. 
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required to appear on the VFD.34  The Additional Recommendations section 
should appear on labeling immediately following the Warnings section. 
The Additional Recommendations section should include the following 
statements:   
The maximum permitted duration(s) of use for <list affected indication(s) 
[and affected regimen(s) as appropriate]> was(were) established according to 
an assessment of information relevant to the characteristics and dynamics of 
this(these) disease(s), including <describe information used: e.g., peer-
reviewed scientific literature, etc.>.  The maximum permitted duration of use 
specified on the labeling is not intended to be routinely ordered, but instead is 
intended to provide the veterinarian with adequate flexibility to use the drug 
consistent with the principles of judicious use. 
Labeling approved for prevention, reduction of incidence, and similar indications 
should include the following statement in the Additional Recommendations 
section: 
Animals may be considered at risk for a disease when transmission of 
existing undiagnosed infections, or the introduction of pathogens, is 
anticipated based on history, clinical judgment, or epidemiological 
knowledge. 
In addition, the Additional Recommendations section should include information 
for each indication, as appropriate, to assist the veterinarian in determining when 
drug feeding should be initiated or stopped in accordance with the approved 
conditions of use and consistent with the principles of judicious use of 
antimicrobials.  Such information should be oriented to the specific indication or 
indication type in question and may include factors to consider regarding when to 
begin the regimen, known risk factors for the disease, or considerations for 
selecting a specific duration of use under different scenarios.  For example, beef 
cattle may spend differing lengths of time in finishing feed yards depending on 
their age and condition when first entering the yard, which may affect the risk 
period or other factors associated with an indicated disease.  Not all indications 
will benefit from such additional information. 
For all indications, sponsors should consider whether the types of additional 
information described in section IV.B. Providing Additional Information for the 
Veterinarian of this guidance would be of value to the veterinarian when 
considering use of the drug or when determining an appropriate duration of use to 
 
34 See 21 CFR 558.6(b)(3) for information that must appear on a lawful VFD.  Among other things, the VFD is 
required to include various information such as cautionary statements necessary for use of the drug in conformance 
with the approval.  See 21 CFR 558.6(b)(3)(xi).  The information in the Additional Recommendations section is 
not intended to be necessary for use of the drug in conformance with the approval. 
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order on the VFD.  Sponsors should include their proposal(s) and any necessary 
supporting information in the G submission.  CVM will also consider this 
question during review of the G submission and may provide comments on the 
proposed changes for labeling revision. 
d.  Inclusion of Antimicrobial Resistance Mitigation Statements 
The labeling for certain drugs or certain indications may benefit from including 
information in the appropriate section(s) of the labeling that supports the 
principles of judicious use by encouraging practices that would minimize the 
development and spread of antimicrobial resistance.  Examples of statements that 
may address this concern include, but are not limited to: 
  Using an antimicrobial of the same drug class for the same indication 
immediately following use of this drug may increase the risk of 
antimicrobial resistance development.  Consider using a drug from a 
different class if available. 
  Using an antimicrobial of the same drug class in the same group of 
animals immediately following use of this drug may increase the risk of 
antimicrobial resistance development.  Consider using a drug from a 
different class if available. 
  After [X] days of therapy, if animals do not show signs of improvement, 
the veterinarian should evaluate the health status of the animals and, based 
on appropriate diagnostics, determine the need to continue antimicrobial 
therapy with this drug or a drug from a different class. 
  Feed this drug only to the number of animals necessary to treat, control, 
or prevent the indicated disease in accordance with the approved 
conditions of use. 
Sponsors are highly encouraged to consider whether inclusion of one or more 
antimicrobial resistance mitigation statements would be appropriate for their 
product labeling and propose them in the G submission.  CVM will also consider 
this question during review of the G submission and may provide comments on 
the proposed changes for labeling revision. 
e.  Additional Labeling Changes 
Sponsors should also plan to incorporate the following revisions to their labeling 
as applicable: 
  Any other labeling changes previously directed by the Agency that have 
not yet been implemented (e.g., storage statement updates). 
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  Revised directions for use for all approved indications that are otherwise 
not affected by this guidance to delete feed continuously (or similar 
wording) to reduce the chance for inadvertent misunderstanding regarding 
the approved duration of use.  The term should be replaced with either 
consecutive days or at every feeding, as appropriate for clarity with 
respect to the approved feeding regimen.  For example, if the directions 
for use currently state, Feed continuously for X to Y days, appropriate 
revisions include, Feed for X to Y consecutive days, and Feed at every 
feeding for X to Y days. 
  The Approved by FDA under NADA # XXX-XXX statement, as 
required in section 502(w)(3) of the FD&C Act.35 
Sponsors should assess whether any of the above changes are warranted for their 
product labeling and include proposed changes in the revised labeling included 
with the G submission or otherwise indicate the changes they intend to make. 
CVM will also consider this during review of the G submission and may provide 
comments on the proposed changes for labeling revision. 
2.  Submit Non-Fee Labeling Supplement 
After CVM has issued a letter regarding planned labeling revisions, as described in 
Step 2 in section VI.A. Timeline for Sponsors Defining a Duration of Use on the 
Labeling of this guidance, sponsors should submit a non-fee labeling supplement 
(STARS C submission, NF subclass code, 180-day review time36) to CVMs Office 
of New Animal Drug Evaluation, Division of Food Animal Drugs (HFV-130).  The 
labeling supplement should include the following, as discussed below: revised 
labeling, Environmental Impact information, and permission for CVM to contact 
sponsors of applications affected by changes to the pioneer application in advance of 
approval of the labeling supplement.  Other technical sections should not need to be 
addressed unless the sponsor makes changes that are outside the scope of this 
guidance. 
a.  Labeling 
 
35 This requirement was added by section 303 of the Animal Drug and Animal Generic Drug User Fee Amendments 
of 2018, Public Law 115-234, and requires the inclusion of this statement on the labeling (except representative 
medicated feed labeling) of approved new animal drugs by September 30, 2023.  For further information, sponsors 
should consult FDAs Resources for Industry webpage, Approved by FDA Labeling Statement for Approved 
New Animal Drugs, https://www.fda.gov/animal-veterinary/resources-you/approved-fda-labeling-statement-
approved-new-animal-drugs. 
36 Sponsors should not check yes for the question on the eSubmitter template that asks if they are submitting a 
Qualifying Labeling Supplement (QLS) because the supplements covered by this guidance will not qualify for a 
60-day review timeframe.  If this option is inadvertently selected, ONADE will change the submission review time 
from 60 to 180 days.  See footnote 26 on page 12 regarding review times. 
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Sponsors should submit a single, clean copy of each revised labeling component 
(i.e., color facsimile or final printed labeling [electronic FPL, eFPL] for the Type 
A medicated article, and representative [Blue Bird] Type B and Type C medicated 
feed labeling, as applicable) and a revised VFD, all reflecting the changes that 
were previously affirmed by CVM. 
b.  Environmental Impact 
Because the sole objective of this guidance is to define the previously undefined 
duration(s) of use for the affected products, these labeling changes are not 
expected to result in an increase in use of the originally approved drug.  
Therefore, sponsors should request, in the labeling supplement, a claim of 
categorical exclusion (CE) from the requirement to prepare an environmental 
assessment (EA) or an environmental impact statement (EIS), pursuant to 21 CFR 
25.33(a), for an action that does not increase the use of the drug.  (Sponsors 
should not claim a CE citing a subcategory of 21 CFR 25.33(a) [e.g., 21 CFR 
25.33(a)(1)] for these actions.)  With the claim of CE, sponsors must37 include a 
statement that, to their knowledge, no extraordinary circumstances exist that may 
significantly affect the quality of the human environment as described in 21 CFR 
25.21.  Sponsors with questions or who are unable to provide this statement 
should contact CVMs Office of New Animal Drug Evaluation, Division of 
Scientific Support, Environmental Team 1 (HFV-161) or Team 2 (HFV-162). 
c.  Permission for CVM to Contact Affected Sponsors 
Sponsors should include permission for CVM to contact sponsors of any affected 
feed-use combinations, proprietary free-choice medicated feeds, and affected 
generic copies of the drug to discuss changes being made to the pioneer drugs 
labeling, in advance of FDAs approval of the pioneer sponsors labeling 
supplement.  For example: 
[Sponsor] gives permission for CVM to contact sponsors of any affected 
feed-use combinations, proprietary free-choice medicated feeds, and affected 
generic copies of this drug to discuss changes being made to this drugs 
labeling, in advance of FDAs approval of this labeling supplement. 
d.  Other Technical Sections 
For the labeling changes recommended in this guidance (i.e., if the only change is 
to establish appropriately defined durations of use for the affected indications as 
recommended in this section of this guidance), it is not necessary for sponsors to 
provide additional information relevant to target animal safety, effectiveness, 
human food safety, or chemistry, manufacturing, and controls (CMC).  Safety and 
CMC related information are not needed because the overall exposure is not 
 
37 See 21 CFR 25.15(a). 
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increasing, and the feed inclusion rates and drug formulations are not changing.  
CVM recognizes that the affected drugs have previously been demonstrated to be 
effective for their respective indications, as reflected by the original approvals.  
Further, CVM considers that although the directions for use for the affected 
indications did not originally define a duration of use, the underlying assumption 
was that these drugs would be used only for the duration needed in any given 
group of animals.  Therefore, labeling changes to define the expected duration of 
use in terms of evidence of disease in the group or the period during which 
animals are at risk for the disease (as applicable to the indication type) are 
understood to be in conformance with the intent of the original approvals and thus 
inherently consistent with the effectiveness information that was used for 
approval.  It is not necessary for sponsors to submit an All Other Information 
technical section because no safety or effectiveness information is required for the 
changes recommended in this guidance.  
Accordingly, sponsors should not need to address these technical sections in a 
presubmission conference or in the supplemental application.  However, if 
sponsors propose changes beyond those recommended in this guidance, additional 
information for one or more of these technical sections may be needed, and a 
labeling supplement may not be an appropriate administrative submission type.  
Sponsors choosing to establish defined durations of use through submission and 
review of safety or effectiveness data (or equivalent information) should not 
submit a labeling supplement as described in this guidance, but instead should 
request a presubmission conference with CVM to discuss technical section 
requirements and the appropriate administrative pathway for approval.  If pioneer 
sponsors choose such an approach, they are strongly encouraged, consistent with 
FDAs goal of establishing appropriately defined durations of use on a timely 
basis for all medically important antimicrobials that currently have undefined 
durations of use, to also provide written permission waiving the pioneer sponsors 
right to marketing exclusivity as discussed in section VII.D. Marketing 
Exclusivity Considerations of this guidance. 
B.  Pioneer (NADA) Feed-Use Combinations 
A feed-use combination is an approved use of two or more active pharmaceutical 
ingredients or Type A medicated articles to create a complete medicated animal feed.  
There are three different types of pioneer feed-use combinations: NADA fixed-ratio 
combination Type A medicated articles, NADA ADAA feed-use combinations, and 
NADA non-ADAA feed-use combinations.  NADA fixed-ratio combination Type A 
medicated articles are those that provide two or more active pharmaceutical ingredients 
as a single Type A medicated article and are discussed in section VII.A. Pioneer Single-
Ingredient and Fixed-Ratio Combination Type A Medicated Articles of this guidance.  
Both NADA ADAA feed-use combinations and NADA non-ADAA feed-use 
combinations provide for two or more individually approved Type A medicated articles 
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to be combined (either directly or via intermediate Type B or Type C medicated feeds) to 
manufacture a Type C medicated animal feed containing a combination of new animal 
drugs.  NADA ADAA feed-use combinations and NADA non-ADAA feed-use 
combinations differ in the way they meet approval requirements.  NADA ADAA feed-
use combinations that meet the qualifying criteria set forth in section 512(d)(4) of the 
FD&C Act and its implementing regulations in 21 CFR 514.4(c)(2) (generally referred to 
as the ADAA combination requirements) are approved using modified requirements for 
establishing safety and effectiveness.  NADA non-ADAA feed-use combinations are 
approved under section 512(d)(1)) of the FD&C Act, after the sponsor provides, among 
other things, a full demonstration of effectiveness and target animal safety when each 
drug is combined in Type C medicated animal feed.  NADA non-ADAA feed-use 
combinations are combinations that were approved before the enactment of ADAA or 
those combinations that do not meet the qualifying criteria set forth in section 512(d)(4) 
of the FD&C Act at the time of approval.  
For the labeling changes recommended in this guidance (i.e., if the only change is to 
establish appropriately defined durations of use for the affected indications as 
recommended in this section of this guidance), it is not necessary for sponsors of feed-use 
combinations to provide additional information relevant to target animal safety, 
effectiveness, human food safety, or CMC. 
1.  NADA ADAA Feed-Use Combinations 
CVM intends to contact sponsors of affected NADA ADAA feed-use combination 
applications after receiving a supplemental application to revise the labeling of the 
affected component Type A medicated article.  Sponsors of these feed-use 
combinations should submit a labeling supplement (C submission, NF subclass code, 
180-day review time38) or otherwise formally initiate the alignment process (i.e., in a 
G submission or presubmission conference request) within 60 days after CVM 
notifies them that the approved conditions of use for the affected component Type A 
medicated article have been or are going to be revised.  Submissions should be 
directed to CVMs Office of New Animal Drug Evaluation, Division of Food Animal 
Drugs (HFV-130). 
CVM does not anticipate that sponsors of affected NADA ADAA feed-use 
combination applications would commonly need to submit proposals to CVM prior to 
submitting their labeling supplements.  CVM will request amendment(s) to the 
labeling supplements as necessary to work with the sponsor towards approval.  
However, in some cases, it may not be readily apparent how best to align the labeling 
of some feed-use combinations with the revised affected Type A medicated article 
labeling.  As such, sponsors may choose to first submit a G submission or request a 
 
38 See footnote 26 on page 12 regarding review times. 
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presubmission conference with CVM to propose changes and obtain CVMs 
comments before then submitting a labeling supplement. 
The labeling supplement for an NADA ADAA feed-use combination should include 
the following: 
a.  Labeling 
Sponsors should submit a single, clean copy of each revised labeling component 
(i.e., representative [Blue Bird] Type B and Type C medicated feed labeling, as 
applicable) and a revised VFD reflecting the changes to align with the affected 
component Type A medicated article. 
b.  Environmental Impact 
Because the sole objective of this guidance is to define the previously undefined 
duration(s) of use for the affected products, these labeling changes are not 
expected to result in an increase in use of the originally approved drug.  
Therefore, sponsors should request, in the labeling supplement, a claim of CE 
from the requirement to prepare an EA or an EIS, pursuant to 21 CFR 25.33(a), 
for an action that does not increase the use of the drug.  (Sponsors should not 
claim a CE citing a subcategory of 21 CFR 25.33(a) [e.g., 21 CFR 25.33(a)(1)] 
for these actions.)   With the claim of CE, sponsors must39 include a statement 
that, to their knowledge, no extraordinary circumstances exist that may 
significantly affect the quality of the human environment as described in 21 CFR 
25.21.  Sponsors with questions or who are unable to provide this statement 
should contact CVMs Office of New Animal Drug Evaluation, Division of 
Scientific Support, Environmental Team 1 (HFV-161) or Team 2 (HFV-162). 
c.  Permission for CVM to Contact Affected Sponsors 
Sponsors should include permission for CVM to contact sponsors of any affected 
generic copies of the drug to discuss changes being made to the pioneer drugs 
labeling, in advance of FDAs approval of the pioneer sponsors labeling 
supplement.  For example: 
[Sponsor] gives permission for CVM to contact sponsors of any affected 
generic copies of this drug to discuss changes being made to this drugs 
labeling, in advance of FDAs approval of this labeling supplement. 
d.  Other Technical Sections 
For the labeling changes recommended in this guidance (i.e., if the only change is 
to establish appropriately defined durations of use for the affected indications as 
 
39 See 21 CFR 25.15(a). 
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recommended in this section of this guidance), it is not necessary for sponsors to 
provide additional information relevant to target animal safety, effectiveness, 
human food safety, or CMC.  It is not necessary for sponsors to submit an All 
Other Information technical section because no safety or effectiveness 
information is needed for the changes recommended in this guidance.  
Accordingly, sponsors should not need to address these technical sections in a 
presubmission conference or in the supplemental application.  However, if 
sponsors propose changes beyond those recommended in this guidance, additional 
information for one or more of these technical sections may be needed, and a 
labeling supplement may not be an appropriate administrative submission type. 
2.  NADA Non-ADAA Feed-Use Combinations 
Sponsors of NADA non-ADAA feed-use combinations40 should follow the steps 
described in section VII.A. Pioneer Single-Ingredient and Fixed-Ratio Combination 
Type A Medicated Articles of this guidance. 
When applicable, sponsors should either include copies of or otherwise reference the 
location of the appropriate right of reference letter(s) in the file.  Previously-
submitted right of reference letters should be referenced by the principal submission 
identification number and submission date. 
C.  Proprietary Free-Choice Medicated Feed Labeling Maintained Under a VMF 
Free-choice medicated feeds41 are those products which contain one or more animal 
drugs and are placed in feeding and grazing areas but are not intended to be fully 
consumed at a single feeding or to constitute the entire diet of the animal.  The approval 
of a proprietary free-choice medicated feed formulation is completed under an NADA 
submitted under section 512 of the FD&C Act.  For the applications affected by this 
guidance, the underlying data, labeling for the proprietary Type C free-choice medicated 
feed, and VFD order(s) to support the approved use are maintained under a VMF. 
CVM intends to contact sponsors of affected proprietary free-choice medicated feeds 
maintained under a VMF when revisions to the labeling for the source Type A medicated 
article are submitted and approved.  The sponsor of the NADA for the proprietary free-
choice medicated feed and the VMF holder should work together to submit the 
 
40 Pioneer feed-use combinations that were originally approved as an NADA non-ADAA feed-use combination are 
not eligible to use the modified requirements offered by section 512(d)(4) when submitting a supplemental 
application. 
41 Free-choice medicated feeds are Type C medicated feeds and are discussed further in GFI #13, Evaluation of 
Effectiveness of New Animal Drugs for Use in Free-Choice Feeds-Medicated Block, (January 1985) and in GFI 
#23, Medicated Free-Choice Feeds - Manufacturing Control, (July 1985). 
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appropriate submissions to revise the proprietary free-choice medicated feed labeling 
within the timeframes described in section VI.A.2 Timeline Step 2 of this guidance. 
Once a defined duration of use is established for the Type A medicated article used to 
manufacture the proprietary free-choice medicated feed and CVM has notified the VMF 
holder of these changes, the VMF holder should submit the appropriate labeling 
component(s) for the Type C proprietary free-choice medicated feed and copies of a 
revised VFD order(s) reflecting the revised conditions of use to the VMF under a C 
submission. 
The submission to the VMF should include a single, clean copy of each revised labeling 
component (i.e., color facsimile labeling) and a revised VFD order.  In addition to the 
changes described for Type A medicated articles in section VII.A. Pioneer Single-
Ingredient and Fixed-Ratio Combination Type A Medicated Articles of this guidance, 
VMF holders should also include any additional revisions that are needed to align the 
proprietary free-choice medicated feed labeling with the Type A medicated article 
labeling. 
The VMF holder should then notify the sponsor of the Type A medicated article NADA 
that the C submission has been submitted to the VMF.  The sponsor of the Type A 
medicated article NADA should then submit a non-fee prior-approval labeling 
supplement (C submission, NF subclass code, 180-day review time42) to the Type A 
medicated article NADA that references the VMF submission identifier and requests the 
approval of the labeling component(s) and VFD order(s) that were submitted to the VMF.  
Submissions should be addressed to CVMs Office of New Animal Drug Evaluation, 
Division of Manufacturing Technologies (HFV-140).43 
D.  Marketing Exclusivity Considerations 
The labeling approach to establishing defined durations of use recommended in this 
guidance would not qualify pioneer sponsors for marketing exclusivity upon approval 
because no safety or effectiveness information is needed.  This will enable sponsors of 
impacted generic applications to immediately implement changes to align with the 
RLNAD product labeling.  
CVM recognizes that in some cases pioneer sponsors may choose to submit safety or 
effectiveness data (or equivalent information) to support a defined duration of use.44  If 
safety or effectiveness data (or equivalent information) is used to support the approval, 
 
42 See footnote 26 on page 12 regarding review times. 
43 The Division of Manufacturing Technologies (HFV-140) will internally reassign these submissions to the 
Division of Food Animal Drugs (HFV-130) for review.  VMF submissions are initially submitted to HFV-140 based 
on how eSubmitter is currently structured.  
44 The technical section requirements and administrative processes that may be involved in such an approach are 
outside of the scope of this guidance.   
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this may qualify the sponsor for 3-year exclusivity under section 512(c)(2)(F)(iii) of the 
FD&C Act.45  The grant of exclusivity would prevent a generic sponsor from adding the 
RLNADs newly-defined duration of use to their labeling until the end of the 3-year 
exclusivity period, that is, the generic product may continue to be marketed during the 3-
year exclusivity period with no defined duration. 
CVM strongly encourages pioneer sponsors who choose to rely on safety or effectiveness 
data to voluntarily waive their 3-year exclusivity in order to permit the submission and 
approval of a supplement from a generic sponsor containing the RLNADs newly-defined 
duration of use.  A waiver of this exclusivity would allow for the durations of use for 
affected generic products to be revised before the end of the 3-year exclusivity period, 
consistent with FDAs goal of establishing appropriately defined durations of use on a 
timely basis for all medically important antimicrobials that currently have undefined 
durations of use.   
Sponsors who intend to waive their 3-year exclusivity should do so in writing, in their 
supplemental application. 
The request for voluntary waiver should include the following language: 
[Sponsor name] voluntarily waives its right to 3-year exclusivity under section 
512(c)(2)(F)(iii) of the Federal Food, Drug, and Cosmetic Act, in connection with the 
defined duration of use that is the subject of this supplemental application. 
Pioneer sponsors who follow the labeling approach described in this guidance (i.e., one 
that does not involve submission of safety or effectiveness data) should not include the 
above language in their supplement because no exclusivity would apply. 
VIII.  Supplemental ANADAs (Generic Drugs) 
Consistent with current practice, if the conditions of use for an NADA for a medically important 
antimicrobial drug are changed, the labeling for any approved ANADA(s) that references the 
original new animal drug application should be revised in a similar fashion.  CVM intends to 
work expeditiously with the sponsors of affected ANADAs to align their products with the 
revised conditions of use specified in the RLNAD (i.e., pioneer) applications.  Sponsors of 
generic applications affected by this guidance should: (1) align their labeling with the revised 
labeling of the RLNAD to reflect a defined duration of use; (2) define a duration of use if 
approval of the RLNAD has been withdrawn; or (3) request voluntary withdrawal of the 
approval of the specific indication(s) with an undefined duration of use or the entire generic 
application as described in section IX. Voluntary Withdrawal of Approval of a Regimen or an 
 
45 Supplemental applications, as described in this guidance, submitted to add the defined duration of use to an 
NADA ADAA feed-use combination would not qualify for marketing exclusivity under section 512(c)(2)(F)(iii) of 
the FD&C Act because they would not contain the types of studies needed to qualify for 3-year exclusivity. 
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Indication with an Undefined Duration of Use or the Entire (A)NADA of this guidance.  These 
options apply even if the affected ANADA is not currently marketed. 
Consistent with section VII. Supplemental NADAs (Pioneer Drugs) of this guidance, this section 
of the guidance assumes that the currently-approved dosage level administered to the animals 
(drug inclusion rate in feed, amount of drug per head or per unit body weight, etc.) and the 
formulation of the product are not changing.  Additionally, this section assumes that the RLNAD 
sponsor either does not qualify for or waives any marketing exclusivity associated with the 
approval of the supplemental application establishing appropriately defined durations of use for 
the RLNAD.  Sponsors of generic products affected by this guidance that do not meet these 
assumptions are encouraged to discuss their proposals with CVM in a presubmission conference. 
A.  Revising Conditions of Use through Conforming Labeling Changes 
CVM intends to contact sponsors of affected ANADAs after a supplemental application 
to revise the labeling of the RLNAD has been received.  Consistent with current practice, 
CVM recommends that the generic sponsor submit a supplemental application to come 
into alignment with the revised labeling of the RLNAD within 60 days after CVM 
notifies the generic sponsor that the approved conditions of use for the RLNAD have 
been or are being revised.  In addition, any future generic sponsor that wants to use a 
pioneer drug as its RLNAD for which the labeling has been revised as recommended in 
this guidance must submit labeling that is the same as the labeling approved for the 
RLNAD, with a few, non-relevant, exceptions.46   
B.  Administrative Recommendations and Submission Content 
Sponsors of affected ANADAs should use eSubmitter to submit a prior-approval labeling 
supplement (C submission, NF subclass code, 270-day review time47) to the Division 
of Generic Animal Drugs in ONADE and indicate that their supplemental application is 
being submitted as recommended by this guidance.  Sponsors should not propose labeling 
changes in this supplement other than those made to the RLNAD labeling, except for any 
additional changes that may be required by the Agency.  The submission should include: 
  A single, clean copy of each affected labeling component (i.e., color facsimile or 
final printed labeling [electronic FPL, eFPL] for the Type A medicated article and 
representative [Blue Bird] Type B and Type C medicated feed labeling, as 
applicable) and a VFD order(s) reflecting the revised conditions of use, revised as 
follows:48 
 
46 See sections 512(c)(2)(A)(vii) and 512(n)(1)(F) of the FD&C Act (21 U.S.C. 360b(c)(2)(A)(vii) and (n)(1)(F)). 
47 See footnote 26 on page 12 regarding review times. 
48 With the exception of minor formatting or layout adjustments as appropriate to revise the conditions of use, 
revisions to the component version date or number, and other changes as described in this guidance, it is not 
recommended under the framework outlined in this guidance that sponsors propose other labeling changes in the 
 
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  Revised conditions of use to include a defined duration of use as described 
o
on the RLNAD labeling; 
  Any other labeling changes necessary to align with the revised RLNAD 
o
labeling; 
  If not previously implemented, addition of or revision to the Approved by 
o
FDA under ANADA # XXX-XXX statement, as required in section 
502(w)(3) of the FD&C Act; and 
  Any other labeling changes previously required by the Agency that were 
o
not yet implemented. 
  A claim of CE under 21 CFR 25.33(a), for an action that does not increase the use 
of the drug.  Sponsors should not cite a subcategory of 21 CFR 25.33(a) [e.g., 21 
CFR 25.33(a)(1)] for these actions.  With the claim of CE, sponsors must49 
include a statement that, to their knowledge, no extraordinary circumstances exist 
that may significantly affect the quality of the human environment as described in 
21 CFR 25.21.  Sponsors with questions or who are unable to provide this 
statement should contact CVMs Office of New Animal Drug Evaluation, 
Division of Scientific Support, Environmental Team 1 (HFV-161) or Team 2 
(HFV-162). 
  Other technical sections/information.  Except in rare cases, CVM does not 
recommend that sponsors of generic applications include any other technical 
sections for approval in these labeling supplements. 
C.  Defining a Duration of Use if Approval of the RLNAD is Withdrawn 
If approval of the RLNAD referenced by an affected generic application has been 
withdrawn, the generic sponsor(s) should follow the process recommended under section 
VII.A. Pioneer Single-Ingredient and Fixed-Ratio Combination Type A Medicated 
Articles or section VII.B. Pioneer Feed-Use Combinations of this guidance, as 
applicable. 
IX.  Voluntary Withdrawal of Approval of a Regimen or an Indication with an 
Undefined Duration of Use from an NADA or Voluntary Withdrawal of the Entire 
(A)NADA 
Sponsors who choose to not establish an appropriately defined duration of use for the affected 
indication(s) on their product labeling should submit a request to either: (1) voluntarily withdraw 
the approval of their entire application without prejudice under 21 CFR 514.115(d); or (2) 
voluntarily withdraw the approval of the regimen(s) or indication(s) with an undefined duration 
 
context of this supplemental application.  Rather, as previously noted, requests to approve other substantive changes 
should be submitted in a separate supplement. 
49 See 21 CFR 25.15(a). 
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of use from their approved application.  Sponsors may contact CVM with any specific questions 
in advance of submitting such requests. 
A.  Withdrawing Approval of a Regimen or an Indication from an NADA 
Requests to withdraw approval of one or more affected regimen(s) or indication(s) 
without withdrawing approval of the entire application should be submitted as a labeling 
supplement (C submission, NF subclass code, 180-day review time50) to CVMs Office 
of New Animal Drug Evaluation, Division of Food Animal Drugs (HFV-130).  The 
labeling supplement should include the following: 
  The sponsors request to withdraw approval of one or more specific regimen(s) or 
indication(s).  The request should be worded as follows: 
<Sponsor Name> voluntarily requests withdrawal of approval of those 
portions of NADA <###-###> pertaining to the following [regimen(s) or 
indication(s)]: [describe the specific regimen(s) or indication(s) being 
withdrawn]. 
  A single, clean copy of each revised labeling component (i.e., color facsimile or 
final printed labeling [electronic FPL, eFPL] for the Type A medicated article, 
and representative [Blue Bird] Type B and Type C medicated feed labeling, as 
applicable) and a revised VFD reflecting the withdrawn regimen(s) or 
indication(s). 
  A claim of categorical exclusion (CE) under 21 CFR 25.33(a) for an action that 
does not increase the use of the drug.  Sponsors should cite only one basis for CE. 
Sponsors should not claim a CE under 21 CFR 25.33(a)(1) for these actions.  
With the claim of CE, the sponsor must51 provide a statement that, to their 
knowledge, no extraordinary circumstances exist that may significantly affect the 
quality of the human environment as described in 21 CFR 25.21. 
  If applicable, written permission for CVM to contact any sponsors of affected 
feed-use combinations, proprietary free-choice medicated feeds, and affected 
generic copies to discuss changes to the pioneer application in advance of 
approval of the supplement.  For example:  
[Sponsor] gives permission for CVM to contact sponsors of any affected 
feed-use combinations, proprietary free-choice medicated feeds, and affected 
generic copies of this drug to discuss changes being made to this drugs 
labeling, in advance of FDAs approval of this labeling supplement. 
 
50 See footnote 26 on page 12 regarding review times. 
51 See 21 CFR 25.15(a). 
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B.  Withdrawing Approval of an Entire Application 
Requests to withdraw approval of the entire application should be submitted to CVMs 
Office of Surveillance and Compliance, Division of Pharmacovigilance and Surveillance, 
Marketed Product Information Team (HFV-244), and should include the following:  
  The sponsors written request to voluntarily withdraw the approval of their entire 
application without prejudice under 21 CFR 514.115(d). 
  The sponsors acknowledgement that their written request shall be construed as a 
waiver of the sponsors opportunity for a hearing in relation to the withdrawal of 
approval.52  
  If applicable, written permission for CVM to contact any sponsors of affected 
generic copies of the drug in advance of publication of notice of the withdrawal of 
approval in the Federal Register (FR).  The sponsor should use the following 
language for this request:  
[Sponsor] grants CVM permission to contact the sponsor(s) of affected 
generic copies (if applicable) in advance of Federal Register (FR) 
publication.  
  A claim of CE from the requirement to prepare an EA or an EIS, pursuant to 21 
CFR 25.33(g), for withdrawal of approval of an NADA or an ANADA or removal 
of a new animal drug from the index.  Other citations should not be used.  With 
this claim of CE, sponsors must53 also include a statement that, to their 
knowledge, no extraordinary circumstances exist that may significantly affect the 
quality of the human environment as discussed under 21 CFR 25.21.  Sponsors 
with questions or who are unable to provide this statement should, before 
submitting their request to voluntarily withdraw approval of the application, 
contact CVMs Office of New Animal Drug Evaluation, Division of Scientific 
Support, Environmental Team 1 (HFV-161) or Team 2 (HFV-162). 
X.  Glossary 
The following terms used in this document are defined for the purposes of this guidance only. 
See the text of the guidance for complete explanation of and context for these terms. 
 
52 See 21 CFR 514.115(d). 
53 See 21 CFR 25.15(a). 
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Term  Definition for Use in This Guidance 
Affected products /  Products / applications that appear on FDAs public list 
affected applications  of medically important antimicrobial drugs administered 
in the feed of food-producing animals, that currently 
have one or more approved indications with an 
undefined duration of use. 
Appropriately defined  The information regarding duration of feeding on the 
duration of use  labeling ensures that the drug is used only when animals 
need it and provides the veterinarian appropriate 
flexibility to use the drug consistent with the labeling in 
a range of scenarios that may be encountered in practice. 
C submission  CVMs STARS [see definition] code for a supplemental 
application to an NADA or ANADA. 
Control (use)  The drug is administered to a group of animals once a 
proportion [see definition] of the animals in the group 
have been diagnosed (based on clinical signs or other 
appropriate diagnostic methods) with the indicated 
disease. 
Downstream application /  Application or file that relies on and conforms to the 
file type  conditions of use established for the application(s) that it 
references.  For purposes of this guidance, downstream 
applications are ANADA Type A medicated articles, 
NADA ADAA feed-use combinations, ANADA feed-
use combinations, and proprietary medicated feeds 
maintained in a Veterinary Master File. 
Expected duration of use  The duration to be ordered by the veterinarian in 
accordance with the labeled directions for use. 
Feed-use combination  A feed-use combination is an approved use of two or 
more active pharmaceutical ingredients or Type A 
medicated articles to create a complete medicated 
animal feed. 
Free-choice medicated  Free-choice medicated feeds are those products which 
feeds  contain one or more animal drugs and are placed in 
feeding and grazing areas but are not intended to be 
fully consumed at a single feeding or to constitute the 
entire diet of the animal.   
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Term  Definition for Use in This Guidance 
G submission  CVMs STARS [see definition] code for a general 
correspondence submission to an application file. 
Maximum permitted  The duration of use stated in the labeling that cannot be 
duration of use  exceeded for a single course of therapy ordered by a 
veterinarian. The maximum permitted duration is not 
intended to be routinely ordered. 
Medically important  Antimicrobial drugs important to human medicine.  
antimicrobial drugs  Appendix A of GFI #152 indicates which antimicrobial 
drugs/drug classes FDA considers medically 
important for purposes of its strategy to promote the 
judicious use of antimicrobial drugs in animals. 
Pioneer products  NADA single-ingredient and fixed-ratio combination 
Type A medicated articles, and NADA feed-use 
combinations that are approved under section 512(d)(1)) 
of the FD&C Act. 
Prevention (use)  The drug is administered to a group of animals, none of 
which have been diagnosed with the indicated disease, 
when transmission of existing undiagnosed infections or 
the introduction of pathogens is anticipated based on 
history, clinical judgment, or epidemiological 
knowledge. 
Proportion  A percentage of animals in a group that is greater than 
0% and less than 100%, unless otherwise specified on 
the labeling. 
STARS  CVMs Submission Tracking and Reporting System. 
Top-level application  Application that may serve as a reference or component 
for one or more downstream applications or files [see 
definition].  For purposes of this guidance, top-level 
applications are NADA Type A medicated articles 
(including fixed-ratio combination Type A medicated 
articles) and NADA non-ADAA feed-use combinations. 
Treatment (use)  The drug is administered only to animals diagnosed 
(based on clinical signs or other appropriate diagnostic 
methods) with the indicated disease. 
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Term  Definition for Use in This Guidance 
Undefined duration of use  The labeling for the identified product includes no 
information regarding duration of feeding or otherwise 
does not provide an appropriately targeted duration of 
use. 
 
34