Defining Durations of Use for Certain Medically Important Antimicrobial Drugs for Food-Producing Animals

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

#273
Defining Durations of Use for Approved
Medically Important Antimicrobial Drugs
Fed to Food-Producing Animals
Guidance for Industry
Submit comments on this guidance at any time. 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 the docket number FDA-2023-D-2925.
For further information regarding this document, contact AskCVM@fda.hhs.gov.
Additional copies of this guidance document may be requested from the Policy and Regulations
Staff, U.S. Food and Drug Administration, Center for Veterinary Medicine, CPK1, 5001 Campus
Drive, College Park, MD 20740-3835,, 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)
February 2026

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Table of Contents
I. 	Introduction ....................................................................................................................... 1
II. 	Background ....................................................................................................................... 2
III. 	Scope................................................................................................................................... 3
IV. 	Objectives........................................................................................................................... 4
A. Appropriately Defining the Duration of Use ............................................................ 5
B. Providing Additional Information for the Veterinarian ......................................... 6
V. 	Voluntary Adoption of Judicious Use Principles ........................................................... 8
VI. 	Timelines for Implementing Changes ............................................................................. 8
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) ......................................................................... 12
A. Pioneer (NADA) Single-Ingredient and Fixed-Ratio Combination Type A
Medicated Articles .................................................................................................... 12
B. Pioneer (NADA) Feed-Use Combinations .............................................................. 24
C. Proprietary Free-Choice Medicated Feed Labeling Maintained Under a VMF 27
D. Marketing Exclusivity Considerations .................................................................... 28
VIII. 	Supplemental ANADAs (Generic Drugs) ..................................................................... 29
A. Revising Conditions of Use through Conforming Labeling Changes .................. 29
B. Administrative Recommendations and Submission Content ............................... 30
C. Defining a Duration of Use if Approval of the RLNAD is Withdrawn ................ 31
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 ......................................................................................................................... 31
A. Withdrawing Approval of a Regimen or an Indication from an NADA ............. 31
B. Withdrawing Approval of an Entire Application .................................................. 32
X. 	Glossary ........................................................................................................................... 33

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Defining Durations of Use for Approved Medically Important
Antimicrobial Drugs Fed to Food-Producing Animals
Guidance for Industry
This guidance represents 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 is intended to 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, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s 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.
1 Judicious use is defined as the optimal selection, dosage, and duration of antimicrobial treatment that results in the
best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal
impact on subsequent resistance. See “Supporting Antimicrobial Stewardship in Veterinary Settings, Goals for
Fiscal Years 2024-2028,” (https://www.fda.gov/animal-veterinary/cvm-updates/fda-releases-plan-supporting-
antimicrobial-stewardship-veterinary-settings-fy-2024-2028).

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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
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 FDA’s 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.
2 https://www.fda.gov/media/79140/download (April 2012).
3 https://www.fda.gov/media/83488/download (December 2013).
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

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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
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
6 “Supporting Antimicrobial Stewardship in Veterinary Settings: Goals for Fiscal Years 2019-2023,”
(https://www.fda.gov/media/115776/download).
7 https://www.fda.gov/animal-veterinary/safety-health/antimicrobial-resistance
8 See Action 1.1.2 on page 7 of FDA’s 5-year action plan for fiscal years 2019-2023.
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 https://www.fda.gov/media/144927/download (January 2021).
11 Including products that are not currently marketed.

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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
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 FDA’s 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
FDA’s 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.
12 Although FDA’s 5-year action plan (fiscal years 2019-2023) 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/judicious-use-antimicrobials/list-approved-medically-important-
antimicrobial-drugs-administered-feed-food-producing-animals-lack
14 See Action 1.3.1 on page 9 of FDA’s 5-year action plan (fiscal years 2019-2023). 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,” (https://www.fda.gov/media/69949/download)
(January 2023). When final, this guidance will represent FDA’s current thinking on this topic.

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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 veterinarian’s oversight of the
product’s feeding to animals in a manner consistent with the principles of judicious use. As
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 describe the approximate duration range that veterinarians should
first consider for the indication (typical duration range) and be bounded by a maximum
permitted duration. The directions for use on the labeling should also 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).
When determining the specific duration to authorize, veterinarians should first consider
whether a duration within the typical duration range on the labeling would be adequate
and appropriate for the animals under consideration. Veterinarians ultimately may
authorize, in accordance with their professional judgment in varying clinical
circumstances, a duration that falls outside of the typical duration range up to the
maximum permitted duration described on the labeling.
The maximum permitted duration of use is the duration that cannot15 be exceeded for a
single course of therapy authorized by a veterinarian. The maximum permitted duration
is not intended to be routinely authorized. 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.
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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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
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 veterinarian’s 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 veterinarian’s 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.
16 A percentage that is greater than 0% and less than 100%, unless otherwise specified on the labeling.

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Relevant labeling information: The veterinarian’s 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
• 	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 veterinarian’s 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 that cannot be practically
mitigated (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

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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 an 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
below. If, after approximately 3 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 types of information should be addressed in labeling
proposals for applicable pioneer17 products: (1) revised directions for use including the
typical duration range and maximum permitted duration of use (see section VII.A.1.a.
Defining the Revised Directions for Use Including Typical Duration Range and
Maximum Permitted Duration); (2) appropriate antimicrobial resistance mitigation
statement(s); and (3) additional information for the veterinarian to consider.
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 approximately 3 years from the date of publication of the final version of
this guidance. To achieve this goal, sponsors should provide 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
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.

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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 one or
more STARS20 G submissions (general correspondence submissions) for CVM
review.21 Sponsors may choose to coordinate with each other if they are interested in
seeking 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 CVM’s Office of New Animal Product 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
maintains 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 G submissions 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(s) no later than 6 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(s) 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(s).
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.
20 STARS is CVM’s Submission Tracking and Reporting System. For information on electronic submission through
eSubmitter, see https://www.fda.gov/animal-veterinary/development-approval-process/electronic-submissions.
21 Sponsors may choose to submit all proposals for a given application in the same G submission, or they may
choose to submit their various proposals across multiple G submissions (e.g., submit a separate G submission for
each impacted indication).

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When review of each 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 each relevant G
submission (for top-level NADAs), or after they are contacted by CVM (for
downstream applications and files), sponsors should submit one non-fee22
supplemental application (labeling supplement) for each affected application to
request approval of the revised conditions of use and associated labeling components.
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
VMFs23 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.
22 Supplemental animal drug applications that do not require safety or effectiveness data (such as the labeling
changes recommended in this guidance) 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.
23 Discussed further in section VII.C. Proprietary Free-Choice Medicated Feed Labeling Maintained under a VMF
of this guidance.

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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.
• 	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 (one
corresponding to each VMF) 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.24
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 from an NADA or Voluntary Withdrawal
of the Entire (A)NADA of this guidance within 1 year following finalization of this
24 The Agency agreed to these review time goals for labeling supplements in the goals letters that accompanied the
2023 reauthorization of the Animal Drug User Fee Act (ADUFA) (https://www.fda.gov/media/116001/download
and the 2023 reauthorization of the Animal Generic Drug User Fee Act (AGDUFA)
(https://www.fda.gov/media/116328/download).

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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
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.25 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 provide
directions for use that are defined in terms of evidence of disease (or risk period for
disease, as applicable) in the group, the typical duration range to be considered, and the
maximum permitted duration of use. 26 The labeling also should provide information as
appropriate that would support the principles of judicious use and minimize the
25 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.
26 See section VII.A.1.a. Defining the Revised Directions for Use Including Typical Duration Range and Maximum
Permitted Duration of this guidance.

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development and spread of antimicrobial resistance,27 and provide additional information
for the veterinarian to consider when authorizing use of the drug.28
To help ensure efficient review of these labeling changes, for each affected application,
sponsors should first submit proposed labeling changes in one or more G submissions for
CVM review and then submit a single labeling supplement for approval, as described in
this section.
1. 	Submit Proposals with Justification to CVM for Review
Sponsors should submit proposals with appropriate justification in one or more G
submissions before submitting the labeling supplement. For each affected indication,
the G submission should include the following, as discussed in this section:
• 	the proposed revised conditions of use including:
o 	the typical duration range veterinarians should first consider for the
indication (along with appropriate justification);
o 	the maximum permitted duration of use (along with appropriate
justification);
• 	appropriate antimicrobial resistance mitigation statement(s);
• 	any additional information for the veterinarian to consider; and
• 	acknowledgement of intent to incorporate any additional labeling changes that
may be needed.
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 one or more G
submissions to each affected application file. These should be submitted to CVM’s
Office of New Animal Product Evaluation, Division of Food Animal Drugs for
review and comment. Sponsors may address all affected indications for a product in
the same G submission or they may choose to address the affected indications across
multiple submissions. Sponsors may choose to request a presubmission conference to
discuss proposals with CVM before submitting the G submission(s). Sponsors are
encouraged to include draft revised labeling for all affected labeling components in
the G submission(s) 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
27 See section VII.A.1.b. Inclusion of Antimicrobial Resistance Mitigation Statements of this guidance.
28 See section VII.A.1.c. Providing Additional Information for the Veterinarian of this guidance.

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submission(s), 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 each G submission, CVM will issue a letter to the sponsor. The
letter will indicate whether CVM generally agrees with the sponsor’s proposals and
will provide additional comments as warranted. CVM will work with sponsors to
review and comment on planned labeling revisions in an efficient manner.
a. 	Defining the Revised Directions for Use Including Typical Duration
Range and Maximum Permitted Duration
For all affected indications across all affected products, the Directions29 section of
the labeling should be revised as follows:
• 	Provide language to ensure that the drug is only used (1) when there is
evidence of disease in the group (in the case of treatment or control
indications), or (2) during the period in which animals are at risk for the
disease (in the case of prevention indications);
• 	Describe the typical duration range that the veterinarian should consider,
and;
• 	State the maximum permitted duration.
Typical Duration Range
The typical duration range encompasses the durations that veterinarians would
authorize for the indication in most circumstances, and should be consistent with
current veterinary standards of practice for the indication. To allow veterinarians
flexibility to deviate from the typical duration range when warranted, this range
should appear on the labeling using the phrasing, “…continue for approximately
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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A to B days….” The Directions section of the labeling should be clear that the
veterinarian is to determine the actual duration to authorize on a VFD for use in a
specific group of animals.
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
authorized by a VFD. The maximum permitted duration of use should appear in a
“Do not feed for more than a [insert maximum duration of use (days)] course of
therapy as authorized by this VFD” 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 authorize,
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 may occasionally 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.
Proposal and Justification
Sponsors should propose the typical duration range and maximum permitted
duration of use for each indication based on typical and potential disease risk
periods, observed disease progress, self-cure timeframes, usual and maximum
time frames to expected outcomes, and other relevant 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 (e.g., statements from veterinarians regarding how long they
currently use the drug), and other such information. If appropriate and the
sponsor chooses to do so, the justification may also draw on existing information
relevant to the drug itself (including studies in the application file that were used
to support the original approval of the indication, or information related to
mechanism of action, pharmacokinetics, and pharmacodynamics), that may help
inform how long the drug should typically be used and the maximum duration
that it may need to be used, to be effective for the indicated disease in commonly
encountered and potential worst-case scenarios.
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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The justification should be comprehensive, focused, balanced, and limit bias. It
should build the argument logically and present information that both supports
and counters (if such information exists) the proposed typical duration range and
maximum permitted duration. 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 must also be included. 31
Sponsors choosing to refer to completed studies that have not yet been submitted
to CVM should only include a study report or summary of relevant observations,
and not include raw data with the justification. For studies previously submitted
to CVM, sponsors may simply refer to the location of the reports by study title or
other identifying information, submission date, and file number.
Format and Phrasing of Revised Directions for Use
For consistency and clarity across affected products, 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 incorporate the typical duration range, the
maximum permitted duration, and (if applicable) preserve any required directions
for use (e.g., a minimum duration) that 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 for approximately A to B days
until the animals no longer require this medication, as determined by the
veterinarian. Do not feed for more than X days.”
31 See 21 CFR 514.1(a).

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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 [currently approved
minimum duration (A)] days up to approximately B days until the animals
no longer require this medication, as determined by the veterinarian. Do
not feed for more than X days.”
If warranted by unique aspects of the disease or drug (e.g., veterinary practice
standards related to the disease or specifics related to the drug’s mechanism of
action), an alternative statement similar to the following is recommended:
“Feed only to animals that are diagnosed with the disease. Begin feeding
after the disease is diagnosed and continue for approximately A to B days
until C days after resolution of clinical signs, as determined by the
veterinarian. Do not feed for more than X days.”
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 “C.”
• 	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 for approximately A to B days 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. Do
not feed for more than X days.”
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 [currently approved
minimum duration (A)] days up to approximately B days 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. Do
not feed for more than X days.”
If warranted by unique aspects of the disease or drug (e.g., veterinary practice
standards related to the disease or specifics related to the drug’s mechanism of
action), an alternative statement similar to the following is recommended:

Contains Nonbinding Recommendations
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“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 approximately A to B days until C
days after an acceptable degree of control has been reached in the group or
until resolution of clinical signs, as determined by the veterinarian. Do not
feed for more than X days.”
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 “C.”
• 	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
of the risk period and continue for approximately A to B days until
animals are no longer at risk, as determined by the veterinarian. Do not
feed for more than X days.”
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 [currently approved minimum
duration (A)] days up to approximately B days until the animals are no
longer at risk, as determined by the veterinarian. Do not feed for more
than X days.”
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(s) 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. Sponsors should appropriately
justify any alternative statements they may choose to propose.
.

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b. 	Inclusion of Antimicrobial Resistance Mitigation Statements
The labeling for affected applications 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. Sponsors should consider antimicrobial resistance risk
mitigation statement(s) that are appropriate for their product and approved use
conditions, including where and under what heading(s) they should appear on the
labeling, and provide their proposal in the G submission(s). CVM will also
consider the need for such statement(s) during review of the G submission(s) and
may provide comments on the proposed changes for labeling revision.
For illustrative purposes, examples of such statements 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.”
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
32 See GFI #181, “Blue Bird Medicated Feed Labels,” (https://www.fda.gov/media/70452/download) (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 but sponsors may propose to include it on the
VFD submitted for approval to serve as a model for aiding communication with
veterinarians and other end users. 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 of use specified on the labeling is not
intended to be routinely authorized, but instead is intended to provide the
veterinarian with adequate flexibility when necessary to ensure effectiveness
while still using the drug consistent with the principles of judicious use. In
determining the specific duration to authorize, the veterinarian should first
consider whether the approximate duration range described in the Directions
is adequate and appropriate for the animals under consideration. The
approximate duration range(s) and maximum permitted duration(s) of use for
<list affected indication(s) [and affected regimen(s) if appropriate]>
was(were) established according to an assessment of information relevant to
the characteristics and dynamics of this(these) disease(s), including <briefly
describe the types of information used: e.g., peer-reviewed scientific
literature, etc.>. ”
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
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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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
authorize on the VFD. Sponsors should include their proposal(s) and any
necessary supporting information in the G submission(s). CVM will also consider
this question during review of the G submission(s) and may provide comments on
the proposed changes for labeling revision.
d. 	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).
• 	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.”
If not previously implemented, sponsors must also revise or add 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(s) or otherwise indicate the changes they intend to make.
CVM will also consider this during review of the G submission(s) and may
provide comments on the proposed changes for labeling revision.
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, see
“‘Approved by FDA’ Labeling Statement Provides Assurance of Safety, Effectiveness of Animal Drugs,”
(https://www.fda.gov/animal-veterinary/cvm-updates/approved-fda-labeling-statement-provides-assurance-safety-
effectiveness-animal-drugs).

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2. 	Submit Non-Fee Labeling Supplement
After CVM has issued all relevant letters regarding planned labeling revisions for a
given application, 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 single non-fee labeling supplement (STARS C submission, NF subclass code, 180-
day review time36) to CVM’s Office of New Animal Product Evaluation, Division of
Food Animal Drugs. 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
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 CVM’s Office of New Animal Product Evaluation, Division of
Statistical and Biological Sciences, Environmental Branch.
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, ONAPE will change the submission review time
from 60 to 180 days. See footnote 24 on page 11 regarding review times.
37 See 21 CFR 25.15(a).

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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 drug’s
labeling, in advance of FDA’s approval of the pioneer sponsor’s 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 drug’s
labeling, in advance of FDA’s approval of this labeling supplement.”
d. 	Other Technical Sections
For supplemental applications that only propose the labeling changes
recommended in 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 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 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

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sponsors choose such an approach, they are strongly encouraged, consistent with
FDA’s 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 sponsor’s
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 (NADA)
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
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)(ii) (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 supplemental applications that only propose the labeling changes recommended in
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,

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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 CVM’s Office of New Animal Product Evaluation, Division of Food
Animal Drugs.
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 each
labeling supplement 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
presubmission conference with CVM to propose changes and obtain CVM’s
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
38 See footnote 24 on page 11 regarding review times.
39 See 21 CFR 25.15(a).

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should contact CVM’s Office of New Animal Product Evaluation, Division of
Statistical and Biological Sciences, Environmental Branch.
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 drug’s
labeling, in advance of FDA’s approval of the pioneer sponsor’s 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 drug’s
labeling, in advance of FDA’s 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 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 (NADA) 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.
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.

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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(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
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(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. In addition to the changes
described for Type A medicated articles in section VII.A. Pioneer (NADA) 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(s) that were submitted to the VMF.
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,”
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-13-evaluation-effectiveness-
new-animal-drugs-use-free-choice-feeds-medicated-block) (January 1985) and in GFI #23, “Medicated Free-Choice
Feeds - Manufacturing Control,” (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-
gfi-23-medicated-free-choice-feeds-manufacturing-control) (July 1985).
42 See footnote 24 on page 11 regarding review times.

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Submissions should be addressed to CVM’s Office of New Animal Product Evaluation,
Division of Manufacturing Technologies.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 for approval (see section
VII.A.2.d. Other Technical Sections of this guidance). This will enable sponsors of
impacted generic applications to immediately implement changes to align with the
RLNAD product labeling.
However, CVM recognizes that in some cases pioneer sponsors may choose to submit
safety or effectiveness data (or equivalent information) to be used for approval of a
defined duration of use.44 If safety or effectiveness data (or equivalent information) is
used for the approval, 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 RLNAD’s 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 RLNAD’s 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 FDA’s 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:
43 The Division of Manufacturing Technologies will internally reassign these submissions to the Division of Food
Animal Drugs for review. VMF submissions are initially submitted to the Division of Manufacturing Technologies
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.
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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“[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 must be revised in a similar fashion.46 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 must align their labeling with the revised labeling
of the RLNAD to reflect a defined duration of use.47 	If approval of the RLNAD has been
withdrawn, sponsors of generic applications should (1) define a duration of use; or (2) 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 Indication with an Undefined Duration of Use from an NADA or
Voluntary Withdrawal of 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
46 See sections 512(c)(2)(A)(vii) and (n)(1)(F) of the FD&C Act (21 U.S.C. 360b(c)(2)(A)(vii) and (n)(1)(F)).
47 Ibid.

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this guidance must submit labeling that is the same as the labeling approved for the
RLNAD, with a few, non-relevant, exceptions.
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 time48) to the Office of
Generic Animal Drugs 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(s) reflecting the revised conditions of use, revised as
follows49:
o 	Revised conditions of use to include a defined duration of use as described
on the RLNAD labeling;
o 	Any other labeling changes necessary to align with the revised RLNAD
labeling;
o 	If not previously implemented, addition of or revision to the “Approved by
FDA under ANADA # XXX-XXX” statement, as required in section
502(w)(3) of the FD&C Act; and
o 	Any other labeling changes previously required by the Agency that were
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 must50
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 CVM’s Office of New Animal Product Evaluation,
Division of Statistical and Biological Sciences, Environmental Branch.
48 See footnote 24 on page 11 regarding review times.
49 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
context of this supplemental application. Rather, as previously noted, requests to approve other substantive changes
should be submitted in a separate supplement.
50 See 21 CFR 25.15(a).

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• 	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 (NADA) Single-Ingredient and Fixed-Ratio Combination Type A
Medicated Articles or section VII.B. Pioneer (NADA) 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
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 time51) to CVM’s Office
of New Animal Product Evaluation, Division of Food Animal Drugs. The labeling
supplement should include the following:
• 	The sponsor’s 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
51 See footnote 24 on page 11 regarding review times.

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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 must52 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 drug’s
labeling, in advance of FDA’s approval of this labeling supplement.”
B. Withdrawing Approval of an Entire Application
Requests to withdraw approval of the entire application should be submitted to CVM’s
Office of Surveillance and Compliance, Division of Pharmacovigilance and Surveillance,
Marketed Product Information Branch, and should include the following:
• 	The sponsor’s written request to voluntarily withdraw the approval of their entire
application without prejudice under 21 CFR 514.115(d).
• 	The sponsor’s acknowledgement that their written request shall be construed as a
waiver of the sponsor’s opportunity for a hearing in relation to the withdrawal of
approval.53
• 	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.”
52 See 21 CFR 25.15(a).
53 See 21 CFR 514.115(d).

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• 	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 must54 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 CVM’s Office of New Animal Product Evaluation, Division of Statistical
and Biological Sciences, Environmental Branch.
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.
Term 	Definition for Use in This Guidance
Affected products /
affected applications
Products / applications that appear on FDA’s public list
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
duration of use
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 use the drug consistent with the labeling in
a range of scenarios that may be encountered in practice.
C submission 	CVM’s 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.
54 See 21 CFR 25.15(a).

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Term 	Definition for Use in This Guidance
Downstream application /
file type
Application or file that relies on and conforms to the
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.
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
feeds
Free-choice medicated feeds 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.
G submission 	CVM’s STARS [see definition] code for a general
correspondence submission to an application file.
Maximum permitted
duration of use
The duration of use stated in the labeling that cannot be
exceeded for a single course of therapy authorized by a
veterinarian. The maximum permitted duration is not
intended to be routinely authorized.
Medically important
antimicrobial drugs
Antimicrobial drugs important to human medicine.
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.

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Term 	Definition for Use in This Guidance
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 	CVM’s 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.
Typical duration range 	The approximate duration range that the veterinarian
should first consider when determining the actual
duration to authorize in accordance with the labeled
directions for use.
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.