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Eligibility Criteria for Expanded 
Conditional Approval of New 
Animal Drugs 
 
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 docket number FDA-2019-D-3361. 
 
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 (HFV-6), Center for Veterinary Medicine, Food and Drug 
Administration, 7500 Standish Place, Rockville MD 20855, and may be viewed on the 
Internet at https://www.fda.gov/animal-veterinary, https://www.fda.gov/regulatory-
information/search-fda-guidance-documents, or https://www.regulations.gov. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
July 2021 Contains Nonbinding Recommendations 
 
Eligibility Criteria for Expanded Conditional Approval of New 
Animal Drugs 
 
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 
AskCVM@fda.hhs.gov. 
 
I.  Introduction 
 
This guidance is intended for sponsors and potential sponsors (you) who may be interested 
in pursuing conditional approval of new animal drug products (hereinafter referred to as 
drugs) for certain major uses in major species under section 571 of the Federal Food, 
Drug, and Cosmetic Act (FD&C Act).  Section 571 of the FD&C Act, as amended by the 
Animal Drug and Animal Generic Drug User Fee Amendments of 2018, now includes 
provisions which expand eligibility for conditional approval beyond minor uses in major 
species and use in minor species (MUMS) to also include certain major uses in major 
species in order to incentivize development of drugs for serious or life-threatening 
conditions or unmet animal or human health needs where a demonstration of effectiveness 
would require a complex or particularly difficult study or studies.  Throughout this 
guidance, the Center for Veterinary Medicine (CVM or we) refers to the process for 
conditionally approving drugs that are not intended for MUMS indications as expanded 
conditional approval.  The term expanded conditional approval does not apply to 
applications for conditional approval involving drugs intended for MUMS indications 
(i.e., MUMS drugs).  
 
The purpose of this guidance is to further clarify the statutory eligibility criteria for 
expanded conditional approval, specifically by defining the following terms that appear in 
section 571 of the FD&C Act: 
  serious or life-threatening disease or condition  
  unmet animal or human health need, and  
  complex or particularly difficult study or studies 
 
CVM intends to describe the procedure for sponsors to use for requesting determinations 
of eligibility for expanded conditional approval in a separate guidance document.  
 
Sponsors and potential sponsors interested in pursuing expanded conditional approval for 
a drug are encouraged to work with CVMs Office of New Animal Drug Evaluation 
2    Contains Nonbinding Recommendations 
(ONADE) early in the drug development process and should contact ONADE for more 
information on this topic.  You may contact AskCVM@fda.hhs.gov if you have questions 
about the expanded conditional approval process. 
 
ONADE project managers (PMs) serve as a central point of contact for drug sponsors and 
potential sponsors and can provide information about the drug review process and 
ONADEs regulatory procedures.  Sponsors or potential sponsors that have questions 
about the expanded conditional approval process and do not have an ONADE PM 
assigned to them may contact the PM team using the CVM mailbox 
CVM.ONADE.PM@fda.hhs.gov. 
 
Throughout this guidance, the term full approval or fully approved is used when 
referring to an approval of an application submitted under section 512(b) of the FD&C 
Act.  The term conditional approval or conditionally approved is used when referring 
to an application for conditional approval submitted under section 571 of the FD&C Act. 
 
In general, FDAs guidance documents do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
 
II.  Background 
 
In 2004, the Minor Use and Minor Species Animal Health Act (MUMS Act) was enacted 
and established section 571 of the FD&C Act (21 U.S.C. 360ccc), allowing for the 
conditional approval of drugs intended for use in minor species (those other than horses, 
dogs, cats, cattle, pigs, turkeys, and chickens) or for minor uses in major species (i.e., 
MUMS drugs).1 For a drug intended for use in a major species to be eligible for 
conditional approval under the MUMS Act, the drug must be intended for a minor use (see 
section 571(a)(1)(A)(i) of the FD&C Act).  The term minor use is defined in section 
201(pp) of the FD&C Act.2 
 
In 2013, in a goals letter FDA prepared in conjunction with the third authorization of its 
animal drug user fee program (ADUFA III),3 FDA agreed to consider whether it would be 
appropriate to pursue possible statutory revisions to expand the concept of conditional 
 
1 In accordance with sections 201(nn) and (oo) of the FD&C Act (21 U.S.C. 321(nn) and (oo)), major species 
means cattle, horses, swine, chickens, turkeys, dogs, and cats; minor species means animals, other than humans, 
that are not major species. 
2 Section 201(pp) of the FD&C Act (21 U.S.C. 321(pp)) states, [t]he term minor use means the intended use of a 
drug in a major species for an indication that occurs infrequently and in only a small number of animals or in limited 
geographical areas and in only a small number of animals annually. 
3 The Animal Drug and Animal Generic Drug User Fee Reauthorization Act of 2013 was signed into law on June 
13, 2013 and became Public Law 113-14. 
3    Contains Nonbinding Recommendations 
approval in section 571 of the FD&C Act to other appropriate categories of drugs that 
would not be eligible for conditional approval under the MUMS provisions of the FD&C 
Act.  Through a public process and working in concert with stakeholders, FDA explored 
the feasibility of the expansion of the conditional approval pathway.   
 
In 2018, Congress enacted legislation reauthorizing FDAs animal drug user fee program 
for an additional 5 years.4  This legislation also amended section 571 of the FD&C Act to 
include provisions for expanded conditional approval (i.e., conditional approval for certain 
non-MUMS drugs) and directed the FDA to issue guidance or regulations to further clarify 
the eligibility criteria for expanded conditional approval.5  In developing the definitions 
CVM is providing in this guidance for the terms serious or life-threatening disease or 
condition and unmet animal or human health need, CVM considered the definitions for 
serious disease or condition and unmet medical need provided in the Guidance For 
Industry (GFI) entitled, Expedited Programs for Serious Conditions  Drugs and 
Biologics that was issued by FDAs Center for Drug Evaluation and Research and its 
Center for Biologics Evaluation and Research in May 2014.6 
 
Conditional approval for MUMS or non-MUMS drugs allows a sponsor to legally market 
a drug after demonstrating the drug is safe and manufactured in accordance with the full 
approval standards, and that there is a reasonable expectation of effectiveness.  The 
sponsor may be able to market the conditionally approved MUMS or non-MUMS drug for 
up to 5 years while gathering the remaining data required to demonstrate substantial 
evidence of effectiveness.  The statute requires annual renewal of the conditional approval 
in order for the conditional approval to remain in effect (see section 571(d) of the FD&C 
Act).  To obtain renewal, the sponsor of the conditionally approved MUMS or non-
MUMS drug needs to be making sufficient progress toward meeting the effectiveness 
standard for full approval (see section 571(d)(2) of the FD&C Act).  
 
The eligibility criteria for expanded conditional approval are discussed below.  
 
III.  Eligibility for Expanded Conditional Approval 
 
A. Statutory Criteria 
 
Section 304 of the Animal Drug and Animal Generic Drug User Fee Amendments of 2018 
amended section 571 of the FD&C Act expanding the conditional approval pathway to 
allow certain non-MUMS drugs to become eligible for conditional approval.  As stated 
above, for purposes of this guidance, CVM refers to the process for conditionally 
approving non-MUMS drugs as expanded conditional approval.  To be eligible for 
 
4 The Animal Drug and Animal Generic Drug User Fee Amendments of 2018 was signed into law on August 14, 
2018 and became Public Law 115-234. 
5 See section 304 of Public Law 115-234. 
6 https://www.fda.gov/media/119293/download 
4    Contains Nonbinding Recommendations 
expanded conditional approval, section 571(a)(1)(A)(ii) of the FD&C Act requires the 
non-MUMS drug to meet the following two criteria: 
1.  The drug is intended to treat a serious or life-threatening disease or condition OR 
addresses an unmet animal or human health need; AND 
2.  A demonstration of effectiveness would require a complex or particularly difficult 
study or studies. 
 
Section 571(a)(3)(A) of the FD&C Act states that the conditional approval pathway 
cannot be used for transgenic animals.  A transgenic animal is defined in section 571(j) 
of the FD&C Act as an animal whose genome contains a nucleotide sequence that has 
been intentionally modified in vitro, and the progeny of such an animal; Provided that the 
term transgenic animal does not include an animal of which the nucleotide sequence of 
the genome has been modified solely by selective breeding.  We note that intentional 
genomic alterations (IGAs) in animals include those that are transgenic, as defined in 
section 571 of the FD&C Act.  However, IGA is a broader term than transgenic and 
may include types of alterations (e.g., deletions) that would not meet the above-cited 
definition. Therefore, IGAs in animals may be eligible for conditional approval.  In 
addition, FDA does not consider an animal containing non-heritable alterations to be a 
transgenic animal within the meaning of section 571(j) of the FD&C Act.  For IGAs and 
other novel technologies, we encourage you to contact CVM to discuss whether your 
product may be eligible for conditional approval. 
 
Section 571(a)(3)(B) of the FD&C Act states that drugs containing an antimicrobial active 
ingredient are not eligible for expanded conditional approval. 
 
Section 571(a)(1)(B) of the FD&C Act directs FDA to further clarify the criteria specified 
in section 571 of the FD&C Act for expanded conditional approval.  In accordance with 
this directive, in section III.B. Definitions below, we are providing clarifications of the 
following terms for the purpose of implementing the expanded conditional approval 
provisions of section 571 of the FD&C Act: 
  serious or life-threatening disease or condition, 
  unmet animal or human health need, and  
  complex or particularly difficult study or studies 
 
B. Definitions 
 
1.  Serious or life-threatening disease or condition 
 
FDA interprets serious or life-threatening disease or condition to mean a disease or 
condition that is associated with morbidity that has substantial impact on day to day 
functioning or is associated with mortality in the target animal.  Short-lived and self-
limiting morbidity will usually not be sufficient, unless the disease or condition is 
persistent or recurrent.  Whether a disease or condition is serious is a matter of clinical 
judgment, based on its impact on such factors as survival, day-to-day functioning, or 
5    Contains Nonbinding Recommendations 
the likelihood that the disease, if left untreated, will progress from a less severe 
condition to a more serious one.  A disease or condition may be considered serious 
based on the magnitude of its effect on the target animals that would receive the drug, 
its potential to affect humans if they were to contract the disease or condition from an 
affected target animal, or its potential to adversely impact the food supply.  
 
The following are considered serious or life-threatening diseases or conditions: 
  A disease or condition associated with mortality or morbidity that has substantial 
impact on day to day functioning in the target animal; or 
  A disease or condition in animals that is zoonotic7 and that presents a risk of a 
 
serious or life-threatening disease or condition to human beings, whether or not it 
also presents a risk of harm to the target animal receiving the drug; or  
  A disease or condition that causes wide-spread morbidity in food-producing 
animals that presents a risk of regional or national disruption to food production, 
even if the effect of the disease or condition on an individual-animal basis is minor. 
 
2.  Unmet animal or human health need   
 
FDA interprets unmet animal or human health need to mean a disease or condition 
whose treatment, control, or prevention is not adequately addressed by available 
therapy.  This is a disease or condition that affects individual or defined groups of 
animals or humans, or a condition that more broadly affects animal or human health 
(e.g., antimicrobial resistance). 
   
For the purpose of this guidance, a disease or condition is one for which treatment, 
control, or prevention  is not adequately addressed by available therapy when: 1) 
available therapy does not exist for the same intended use proposed for the drug, or 2) 
available therapy does exist for the same intended use but the drug for which expanded 
conditional approval is sought is reasonably expected to provide a meaningful 
advantage over available therapy. 
For the purpose of this guidance, available therapy means a product that is approved 
under section 512 of the FD&C Act, licensed by the U.S. Department of Agriculture, or 
registered by the Environmental Protection Agency, and is currently being marketed in 
the United States, for the same intended use in the same species as the proposed drug 
for which expanded conditional approval is sought.  
It should be noted that extralabel use of an approved animal or human drug does not 
qualify as an available therapy because safety and substantial evidence of 
effectiveness have not been established for the extralabel use.  In addition, 
 
7 Zoonotic diseases (also known as zoonoses) are caused by infections that are shared between animals and people.  
6    Contains Nonbinding Recommendations 
conditionally approved drugs are not considered available therapy because substantial 
evidence of effectiveness has not been demonstrated.8  
 
For the purpose of this guidance, meaningful advantage means that the drug for 
which expanded conditional approval is sought is reasonably expected to provide one 
or more of the following advantages over available therapy.  Such a product would: 
a.  provide clinically relevant improved effectiveness on an outcome of the involved 
disease or condition when compared to the available therapy;  
b.  provide a clinically relevant beneficial effect on the disease or condition that is not 
provided by available therapy for that disease or condition; 
c.  provide comparable effectiveness on an outcome of the involved disease or 
condition in animals that cannot tolerate the available therapy;  
d.  provide effectiveness comparable to available therapy, while improving safety.  For 
example: (i) avoiding serious toxicity that occurs with available therapy, (ii) 
avoiding less serious toxicity that is common and causes discontinuation of 
treatment for a serious disease or condition, (iii) reducing the potential for harmful 
drug interactions; 
e.  provide for safe administration with other therapies that are necessary for an 
improved beneficial effect on an outcome of the involved disease or condition when 
available therapy cannot. 
 
3.  Complex or particularly difficult study or studies 
 
CVM intends to determine whether a study or studies is complex or particularly 
difficult on a case-by-case basis by considering the extent to which one or more of the 
following factors apply to demonstrating substantial evidence of effectiveness: 
a.  the nature of the disease or condition makes it unusually time consuming or difficult 
to enroll sufficient numbers of eligible animals to provide substantial evidence of 
effectiveness.  Among other possible factors, CVM intends to consider the degree 
to which the following factors apply in making this determination: the sporadic 
occurrence of the disease or the condition, the unpredictability of the occurrence or 
outcome of the disease or condition, the difficulty in diagnosing the disease or 
condition, and the lack of feasible alternatives such as induced disease model 
studies.  In determining whether it is unusually time consuming or difficult to enroll 
sufficient numbers of eligible animals based upon the nature of the disease or 
condition, other factors limiting enrollment that are not based upon the nature of the 
disease or condition (e.g., owner reluctance to enroll animals, safety concerns 
related to the drug that cause stringent inclusion criteria) will not be considered. 
 
8 As with conditionally approved new animal drugs, other conditionally available products (e.g., conditionally 
licensed animal biologics) also are not considered to be available therapy. 
7    Contains Nonbinding Recommendations 
b.  the demonstration of effectiveness is unusually difficult or complex due to logistical 
challenges, such as needing an unusually large number of animals in the study or 
studies or the need for use of advanced or complicated tests.    
c.  it is necessary to develop and qualify effectiveness endpoints (e.g., clinical 
endpoints, biomarkers) to conduct the study or studies. 
d.  it is necessary to develop and validate or qualify novel methods to adequately 
evaluate effectiveness outcomes (e.g., complex animal models, technologies, or 
diagnostic tests).   
e.  the endpoint being evaluated is a delay in progression of a chronically progressive 
disease or condition where evaluation of effectiveness for an individual animal will 
likely take an extended period of time (typically a year or more).  CVM intends to 
take into consideration the frequency and complexity (including logistical or 
technical difficulty) of monitoring the disease or condition during the study when 
considering this factor. 
f.  there is a need to evaluate the treatment of a disease or condition over an extended 
period of drug administration where evaluation of effectiveness for an individual 
animal will likely take an extended period of time (typically a year or more).  CVM 
intends to take into consideration the frequency and complexity (including logistical 
or technical difficulty) of monitoring the disease or condition during the study when 
considering this factor. 
g.  the drug will be indicated for mitigating transmission of a zoonotic disease from 
animals to humans and it is necessary to conduct a study(ies) to evaluate the human 
aspect of effectiveness. 
 
 
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