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GUIDANCE FOR INDUSTRY 
 
SMALL ENTITIES COMPLIANCE GUIDE 
 
The Index of Legally Marketed Unapproved New Animal Drugs 
for Minor Species 
 
(This guidance replaces the version dated September 1, 2010.  This guidance updates contact 
information and reflects minor formatting changes.) 
 
Submit comments on this guidance at any time.  Submit written comments to the Division  of 
Dockets Management (HFA-305), Food and Drug Administration,  5630 Fishers Lane, Room 
1061, Rockville,  MD 20852.  Submit electronic comments on the guidance to 
http://www.regulations.gov.   All comments should be identified  with Docket No. FDA-2010-D-
0435. 
 
For questions regarding this guidance document, contact Dorothy Bailey, Office of Minor Use 
& Minor Species Animal Drug Development (HFV-50), Center for Veterinary Medicine, Food 
and Drug Administration,  7500 Standish Place, Rockville,  MD 20855, 240-402-0565;  email:  
dorothy.bailey@fda.hhs.gov. 
 
Additional  copies of this guidance document may be requested from the Communications  Staff 
(HFV-12), Center for Veterinary Medicine, Food and Drug Administration,  7519 Standish Place, 
Rockville,  MD 20855, and may be viewed on the Internet at 
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIn 
dustry/default.htm  or http://www.regulations.gov. 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine 
July 2014 
    Contains Nonbinding Recommendations 
Guidance for Industry 
Small Entities Compliance Guide 
 
The Index of Legally Marketed Unapproved New Animal Drugs for Minor Species 
 
This guidance represents the Food and Drug Administrations (FDAs) current 
thinking on this topic.  It does not create or confer any rights for or on any person and 
does not operate to bind FDA or the public.  You can use an alternative approach if the 
approach satisfies the requirements of the applicable statutes and regulations.  If you 
want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the 
appropriate number listed on the title page of this guidance. 
 
 
I.  Background 
 
On December 6, 2007 (72 FR 69108), FDA published  a final rule in the Federal Register, 
entitled Index of Legally Marketed Unapproved New Animal Drugs for Minor Species.  This 
final rule implements  section 572 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 
which provides for a public  index listing  of legally  marketed unapproved new animal drugs for 
minor species of animals (species other than cattle, horses, swine, chickens, turkeys, dogs, and 
cats).  Within limitations  established by the statute, such indexing  provides a basis for legally 
marketing an unapproved new animal drug intended for use in a minor species. 
 
FDA has prepared this Small Entities Compliance Guide in accordance with section 212 of the 
Small Business Regulatory Enforcement Fairness Act of 1996 (Public Law 104-121).  This 
document is intended to provide guidance on the requirements of Title 21, Code of Federal 
Regulations,  new Part 516, subpart B. 
 
FDAs guidance documents, including  this guidance, do not establish legally  enforceable 
responsibilities.   Instead, guidances describe the Agencys current thinking  on a topic and 
should be viewed only as recommendations,  unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidances means that something 
is suggested or recommended, but not required. 
 
II.  Purpose 
 
What is Indexing? 
 
Indexing refers to the status that certain new animal drugs can achieve under the provisions 
of section 572 of the Federal Food, Drug and Cosmetic act (FFDCA or the act), which were 
added to the act by the Minor Use and Minor Species Animal Health Act of 2004 (MUMS 
act) (21 U.S.C.  360ccc-1, Index of Legally Marketed Unapproved New Animal Drugs for 
Minor Species). The purpose of indexing  is to allow an additional  means of legally 
marketing new animal drugs intended for use only in minor species and that have not been 
approved or conditionally  approved through the new animal drug approval process under 
section 512 or the conditional  approval process under section 571 of the act for the same 
intended use. 
2  Contains Nonbinding Recommendations 
III.  Questions and Answers 
 
Which animal drugs are eligible for Indexing? 
 
Only new animal drugs intended for use in non-food producing minor species are eligible  for 
indexing,  except that new animal drugs intended for use in early, non-food life stages of some 
food-producing  minor species may be eligible  for indexing  under very limited  circumstances 
(sec. 572(a)(1) of the act) (21 U.S.C.  360ccc-1(a)(1)).  An example might be the treatment 
of non-edible  fish eggs of edible fish species. 
 
Major species are dogs, cats, horses, cattle, swine, turkeys, and chickens.  All other species 
(other than humans) are minor species (sec. 201(nn) of the act) (21 U.S.C.  321(nn)).  Drugs 
intended for use in hundreds of non-food producing minor species may be eligible  for indexing; 
for example, drugs intended for use in most minor species companion animals (such as ferrets, 
hamsters, pet birds, or ornamental fish), most minor species laboratory animals, and most minor 
species maintained in zoos or similar facilities. 
 
A new animal drug cannot be indexed if it is already approved or conditionally  approved in 
the same dosage form for the same intended use in the same minor species (sec. 572(c)(2)(A) 
of the act) (21 U.S.C.  360ccc-1(c)(2)(A)). 
 
An animal drug that is contained in or is a product of a transgenic animal cannot be indexed 
(sec. 572(a)(2) of the act) (21 U.S.C.  360ccc-1(a)(2)). 
 
How does the Indexing process work? 
 
The basic elements of the overall indexing process are relatively  straight-forward. You must 
go through three steps or processes in order to add a new animal drug to the index (sec. 572(c) 
and (d) of the act) (21 U.S.C.  360ccc-1(c) and (d)).  After a new animal drug is indexed, 
there are two processes to assure continued safety and effectiveness while the indexed new 
animal drugs are on the market (sec. 572(e)(3) and (i) of the act) (21 U.S.C.  360ccc-1(e)(3) 
and (i)). 
 
Step 1  Determination of Eligibility:  The first step in the indexing  process involves a 
request for the FDA to determine that a specific new animal drug for one or more intended 
uses is eligible for indexing  (sec. 572(c) of the act) (21 U.S.C.  360ccc- 1(c)) (21 CFR 
516.129).  In this step, the agency needs information  from the requestor to characterize the 
nature of the drug proposed for indexing  and to support a determination  of several aspects of 
product safety as well as the requestors manufacturing  capability,  including: 
 
1)  Identification  of the minor species for which use is intended; 
 
2)  Information regarding drug components and composition; 
 
3)  A statement of intended use(s); 
 
3  Contains Nonbinding Recommendations 
4)  A statement of proposed conditions  of use, including  dosage, route of 
administration,  contraindications,  warnings, etc.; 
 
5)  A brief discussion of the need for the drug; 
 
6)  An estimate of anticipated annual distribution  of the drug expressed as total 
quantity of active ingredient; 
 
7)  Information to establish that the drug is intended for use only in:  non-food 
producing  minor species where there is a reasonable certainty that humans or food- 
producing  animals will not consume the treated animal; or an early, non-food life 
stage of a food-producing minor species in a hatchery, tank, or pond where there is 
information  to demonstrate food safety in accordance with sec. 512(b) of the 
FFDCA (21 U.S.C.  360(b)); 
 
8)  A description of manufacturing methods and controls that shows the requestor 
understands current good manufacturing practices (cGMPs); 
 
9)  An environmental  assessment or a claim for categorical exclusion from an 
environmental  assessment (see 21 CFR Part 25); 
 
10)  Information to support safety to individuals  exposed to the drug during 
manufacture and use; 
 
11)  The name and address of the contact person or permanent-resident U.S. agent. 
 
Step 2 - Establishing an Expert Panel:  If a new animal drug is determined to be eligible  for 
indexing,  the second step in the indexing  process is for a requestor to identify a panel of at least 
three experts qualified  to review the target animal safety and effectiveness of the specified new 
animal drug for its intended use(s).  The names and qualifications  of potential panelists (21 CFR 
516.141(c)(2)) and information  regarding any potential conflicts of interest (21 CFR 
516.141(g)(3)) must be submitted to the agency for a determination  of whether the proposed 
panel is acceptable to FDA to review the specified new animal drug for its intended use(s).  
Panel members may be paid a reasonable fee for services by the requestor (21 CFR 
516.141(g)(4)).  They will not be paid by the FDA (sec. 572(d)(3) of the act) (21 U.S.C.  
360ccc-1(d)(3)). 
 
When a potential qualified  expert panel has been identified,  the requestor must provide potential 
panel members with a copy of section 572 of the FFDCA and a description  of their intended 
duties and responsibilities,  obtain from each potential panel member a comprehensive 
curriculum vitae and certification that they have read and understood the information  provided 
to them, and inform each potential panel member of the need to provide information  regarding 
potential conflict of interest to the FDA. Information obtained from panel members, must then 
be submitted to the FDA for review.  Once a potential panel is accepted by FDA, the requestor 
must provide the panel with all information,  including  anecdotal information,  known to the 
requestor that is relevant to a determination  of the target animal safety and effectiveness of the 
4  Contains Nonbinding Recommendations 
new animal drug, and the requestor must notify FDA of the name of the panel leader (21 CFR 
516.141(c)). 
 
Expert panel members must (21 CFR 516.141(e)): 
 
1)  assure, and certify to the requestor and the agency, that no conflict of interest exists 
with respect to the particular new animal drug under review by the panel; 
 
2)  act in accordance with generally accepted professional and ethical business 
practices; 
 
3)  review all relevant available information  regarding the safety and effectiveness of 
the new animal drug under review; 
 
4)  participate in the preparation of, and sign or otherwise approve in writing, a written 
report of the findings  of the panel. 
 
The written report of the panel must include (21 CFR 516.143): 
 
1)  a description  of the panels evaluation of all information  reviewed; 
 
2)  citations to or summaries of all information  reviewed; 
 
3)  the panels opinion  regarding whether the benefits of the new animal drug 
reviewed outweigh the risks to the target animal, taking into account the harm 
being caused by the absence of an approved or conditionally  approved new animal 
drug for the intended use in the minor species in question and, if it is the 
unanimous opinion  of the panel that benefits outweigh risks; 
 
4)  draft labeling  that includes conditions  of use deemed necessary by the panel to 
assure that the benefits of the reviewed new animal drug outweigh the risks; 
 
5)  a recommendation  regarding whether use of the reviewed new animal drug should 
be limited  to the supervision  of a licensed veterinarian. 
 
Step 3  Request for addition to the Index:  The requestor must forward the qualified  expert 
panels findings  to the FDA for review and concurrence together with the following  (21 CFR 
516.145): 
 
1)  a copy of FDAs written determination  of eligibility  for indexing; 
 
2)  a copy of FDAs written determination  that the qualified  expert panel is acceptable; 
 
3)  a proposed index entry meeting the requirements of 21 CFR 516.157; 
 
4)  proposed labeling; 
5  Contains Nonbinding Recommendations 
5)  anticipated annual distribution  of the new animal drug; 
 
6)  a written commitment to manufacture the new animal drug in accordance with 
cGMPs; 
 
7)  a written commitment to label and promote the new animal drug only in 
accordance with the index entry; 
 
8)  the name and address of the contact person or permanent-resident U.S. agent; 
 
9)  a draft Freedom of Information summary. 
 
The agency will file a request for indexing,  if it meets the requirements of 21 CFR 516.145,  and 
will grant a request for addition  to the index provided it meets all of the following  conditions  (21 
CFR 516.149): 
 
1)  the same drug in the same dosage form for the same intended use is not approved 
or conditionally  approved; 
 
2)  there is no new information  indicating  that the new animal drug no longer meets 
the conditions  for eligibility  for indexing; 
 
3)  the request for indexing  contains all of the information  required by 21 CFR 
516.145; 
 
4)  the qualified  expert panel continues to meet all of the selection criteria in 21 CFR 
516.141; 
 
5)  the written report is sufficient to permit FDA to determine that the benefits of using 
the new animal drug for the proposed use in a minor species outweigh its risks to 
the target animal, taking into account the harm caused by the absence of an 
approved or conditionally-approved  new animal drug for the minor species in 
question; 
 
6)  the request does not contain any untrue statement of a material fact. 
 
The Index entry will be made publicly available on the FDA Website and each index listing  will 
identify:   the holder of the listing  and the new animal drug, the intended use(s) and conditions  of 
use of the new animal drug, a copy of the labeling  and the FOI summary, and any conditions  or 
limitations  regarding the use of the new animal drug (21 CFR 516.157). 
 
After a new animal drug is indexed, the holder of an index listing  will need to maintain 
records of all information  pertinent to the safety or effectiveness of the new animal drug, and 
will also need to submit reports of adverse events, manufacturing defects and other 
information  associated with the new animal drug as follows (21 CFR 516.165): 
 
6  Contains Nonbinding Recommendations 
1)  to the nearest FDA District Office or resident post, a three-day indexed drug field 
alert report regarding any product or manufacturing defect that may result in 
serious adverse drug events within three working days of learning of the defect; 
 
2)  to the Director, OMUMS, a fifteen-day indexed drug alert report on each serious, 
unexpected adverse drug event regardless of the source of the information  within 
fifteen working days of learning of the event; 
 
3)  to the Director, OMUMS, on or within 60 days after the anniversary date of the 
letter granting a request for indexing,  an annual indexed drug experience report 
containing  the number of units of each size, strength or potency distributed during 
the reporting period, a summary of any changes in labeling  or manufacturing 
processes during the reporting period (and copies of labeling  if revised), any non- 
clinical  laboratory studies and clinical  data, reports of adverse drug experiences, 
and any other information  pertinent to the safety or effectiveness of the new animal 
drug not previously  reported. 
 
If holders of index listings  need to change the conditions  of an existing index listing  due to 
adverse drug events or product/manufacturing  defects (urgent changes) or wish to expand the 
scope of an index listing,  for example, by adding new intended uses or extending existing 
intended uses to more minor species (significant  changes), they must do so by submitting  a 
request to modify the index listing  in accordance with the requirements of 21 CFR 516.161. 
 
Does my firm need to be registered and my product drug listed as a condition of 
legally distributing an indexed drug? 
 
Manufacturers of indexed drugs must register and drug list. See 21 CFR 207.20 and 207.21 for 
information  regarding registration and drug listing  requirements. 
 
Do indexed drugs or medicated articles need to comply with cGMPs? 
 
Yes.  In the case of indexed new animal drugs, requestors are required to provide a description 
of the manufacturing,  processing, and packing process, including  methods and controls, for the 
new animal drug proposed for indexing.   This must include sufficient detail for the FDA to 
determine that the requestor understands cGMPs (21 CFR 516.129(b)(8)).  This description 
will be considerably less lengthy than the information  on cGMPs needed in a new animal drug 
application  (NADA) under  512(b) of the FFDCA, i.e., it may be on the order of a 20 to 30 
page description of the manufacturing process rather than the hundreds of pages of information 
needed to support drug approval. 
 
Can new animal drugs intended for use in making medicated feeds be indexed? 
 
Yes.  Indexed drugs may be used to manufacture medicated feed (21 CFR 558.3(b)(2) and 
558.5(c)).  Indexed drugs for use in feed may either be marketed over- the-counter (OTC) or as 
veterinary feed directive (VFD) products depending  on the conditions  of use established by the 
qualified  expert panel and the FDA (21 CFR 516.143(f) and 558.6). 
7  Contains Nonbinding Recommendations 
Are mills that produce feeds from indexed articles subject to feed mill licensing? 
 
Mills producing  animal feeds from indexed drugs are subject to feed mill  licensing in 
accordance with the same criteria that apply to approved new animal drugs.  See 21 CFR 
558.3, 558.4, and part 515 for further information. 
 
Can foreign firms get drugs indexed in the U.S.? 
 
Yes, but foreign firms must have a permanent-resident U.S. agent in accordance with 21 
CFR 516.119. 
 
Must I have a Notice of Claimed Investigational Exemption for a New Animal Drug for 
Index Listing? 
 
If you need to perform studies to support safety or effectiveness, you must do so under an 
Investigational  New Animal Drug (INAD) file.  Studies performed using a new animal drug 
intended for investigational  use in minor species must be performed in accordance with the 
requirements of 21 CFR part 511 as modified for the indexing  process by 21 CFR 516.125.  
However, many new animal drugs may be able to be indexed on the basis of currently available 
information  and further investigational  studies will not be necessary. 
 
Because there is a connection between establishing  an INAD file and user fees, see the next 
question as well. 
 
Do animal drug user fees apply to the indexing process? 
 
There are no user fees specifically  associated with the indexing  process. However, if it is 
necessary to establish an INAD file to provide for investigational  studies to support indexing,  a 
waiver of user fees needs to be requested. Requesting the waiver prior to establishing  the INAD 
file will prevent assessment of any user fees. Because indexing  applies only to products intended 
for use in minor species, a user fee waiver will  be granted. See CVM Guidance for Industry #170 
and #173 for information  regarding the user fee waiver process. 
 
How do I get started with the indexing process? 
 
Read the regulations appearing at 21 CFR 516.111 to 516.171 carefully, and follow them to the 
best of your ability.   The regulations  describe the indexing  process and its various requirements 
in significant  detail.  The agency expects to make additional  information  regarding the indexing 
process available in the form of expanded guidance documents as the need arises. 
 
Who can I call for assistance? 
 
Call the Office of Minor Use & Minor Species Animal Drug Development (OMUMS) at 240-
402-0565.  This Office exists for the sole purpose of facilitating  the approval, conditional 
approval or indexing  of new animal drugs intended for minor species or minor use in major 
species.  The Office is responsible  for designation,  indexing,  minor use determinations,  and 
outreach to MUMS stakeholders. 
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