#132 
 
Administrative Applications 
and the Phased Review Process 
 
Guidance for Industry 
 
This version of the guidance replaces the version made available in May 2015. 
This document has been revised to update contact information and correct a factual and 
typographical error. 
 
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, Room 1061, Rockville, MD 
20852.  All comments should be identified with the Docket No. FDA-2002-D-0147 (formerly 
02D-0449). 
 
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 either 
https://www.fda.gov/AnimalVeterinary/default.htm or https://www.regulations.gov/. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine 
May 2018 
    Contains Nonbinding Recommendations 
Table of Contents 
 
 
I.  INTRODUCTION................................................................................................. 3 
II.  BACKGROUND ................................................................................................... 3 
III.  DEFINITIONS ...................................................................................................... 4 
IV.  THE PHASED REVIEW PROCESS .................................................................. 4 
V.  DESCRIPTIONS OF THE TECHNICAL SECTIONS .................................... 7 
A.  For pioneer applications ................................................................................. 7 
B.  For generic applications ................................................................................. 9 
VI.  SUBMITTING AN ADMINISTRATIVE (A)NADA ......................................... 9 
VII.  TIME FRAME FOR REVIEW ......................................................................... 10 
A.  Administrative NADA .................................................................................. 10 
B.  Administrative ANADA ............................................................................... 11 
VIII.  PATENT TERM RESTORATION ISSUES .................................................... 11 
   
2  Contains Nonbinding Recommendations 
Administrative Applications 
and the Phased Review Process 
 
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 defines: 
 
1.  the phased review process for reviewing application-level information during the 
investigational period of new animal drug development, 
 
2.  an administrative new animal drug application (NADA) or abbreviated new animal 
drug application (ANADA), the content, the procedures a sponsor should follow to 
submit such an application, and the intended time frame for its review. 
 
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 
 
The Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C.  321, et seq.) prohibits 
the introduction into interstate commerce of new animal drugs that are not the subject of an 
approved new animal drug application (NADA).1  Further, sections 512(b)(1) and 512(n)(1) of 
the FD&C Act describes the information that must be submitted as part of an NADA or 
ANADA, respectively. 
 
The Center for Veterinary Medicine (CVM) encourages sponsors to submit data for review at the 
most appropriate and productive times in the drug development process.  Rather than submitting 
all data for review as part of a complete application, we have found that the submission of data 
supporting discrete technical sections during the investigational phase of the new animal drug is 
the most appropriate and productive.  This phased review of data submissions has created 
                                                 
1 To be legally marketed, a new animal drug must be the subject of either an approved application under Section 512(b) of the 
FD&C Act, a conditional approval under section 571 of the FD&C Act, or an index listing under section 572 of the FD&C Act. 
3  Contains Nonbinding Recommendations 
efficiencies for CVM and the animal pharmaceutical industry.  These increased efficiencies have 
facilitated the approval of both pioneer and generic new animal drugs. 
 
This guidance defines what an administrative (A)NADA is, defines and describes the phased 
review process, and briefly discusses how sponsors should submit an administrative (A)NADA 
and the time frame for review. 
 
III.  DEFINITIONS 
 
The phased review of data submissions is a process a sponsor may voluntarily use to complete 
any or all of the technical sections (see section V for a complete list of required technical 
sections) required for approval of a new animal drug before submitting an application.  The 
phased review process occurs during the investigational phase of the animal drug development 
process.  Specifically, it is when a sponsor submits data and information in support of the various 
technical sections to their investigational file (i.e., investigational new animal drug (INAD) file 
for pioneer animal drug products or generic investigational new animal drug (JINAD) file for 
generic animal drug products) for CVM review and acceptance. 
 
An administrative (A)NADA is an original or supplemental new animal drug application 
(NADA) or abbreviated new animal drug application (ANADA) submitted after all technical 
sections necessary to fulfill the requirements for the approval of the new animal drug under 21 
CFR 514.1 have been reviewed by CVM and CVM has issued a technical section complete letter 
for each of the required technical sections.  The administrative (A)NADA is the culmination of 
the completion of the phased review process work. 
 
IV.  THE PHASED REVIEW PROCESS 
 
The use of the phased review process to review data supporting a technical section of a pioneer 
or generic new animal drug application is a voluntary program.2  A sponsor may submit a phased 
review data submission containing all or part of the data or information needed to address the 
requirements of one technical section of the application for review during the investigation of the 
animal drug.  There are multiple ways to navigate the phased review process (e.g., technical 
sections submitted at the same time or submissions that contain data for a portion of the technical 
section); therefore, CVM recommends sponsors use the presubmission conference process to 
discuss specific details regarding the content and timing of each technical section.  The 
requirements under 21 CFR 514.1 equally apply to all applications whether data were submitted 
for phased review or not.  The option to phase the review of data submissions applies to all 
original and supplemental applications and can be exercised up to the point at which the sponsor 
submits the application. 
 
   
                                                 
2 In deciding whether to seek approval of a new animal drug by taking advantage of the phased review of data submissions or by 
submitting all data at one time within the application, a sponsor should consider all advantages and disadvantages of each 
mechanism for approval before submitting data for CVMs review.  For example, a sponsor should consider whether seeking 
approval of a new animal drug under phased review will affect the extension of a patent term.  See the discussion in section VIII 
of this guidance. 
4  Contains Nonbinding Recommendations 
If a sponsor exercises the option to use the phased review process: 
 
  Each phased review submission should contain information and data relating to only one 
technical section.  Sponsors should include all relevant draft labeling and all pertinent 
information they have at the time they submit each technical section.  This facilitates 
FDAs review of the labeling technical section and CVMs preparation of the Freedom of 
Information (FOI) Summary. 
 
  Sponsors are encouraged to contact their ONADE project manager regarding what 
information and data should be submitted together and how to make a submission.  
Alternatively, if the sponsor does not have an ONADE project manager, contact the 
appropriate review division to discuss informational requirements. 
 
  Each phased review submission should be submitted during the investigation of the new 
animal drug and filed in the appropriate (J)INAD file established by CVM for the new 
animal drug. 
 
  The phased review submission to CVM may be made in paper or electronically using the 
eSubmitter tool.  CVM encourages sponsors to use the eSubmitter electronic submission 
tool.  The use of the eSubmitter tool may confer certain review timeline advantages to 
certain sponsors.  The eSubmitter tool provides sponsors with immediate electronic 
receipt confirmation, immediate electronic transmission of CVMs response, and includes 
templates for the various types of submissions to help sponsors ensure they include all 
necessary information.  Sponsors are encouraged to visit 
https://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/UserFees/default.
htm for current eligibility and requirements information contained in the current Goals 
Letters for the user fee programs. 
 
  If there are changes in the product development plan during the phased review process 
(e.g., indication, dosage, duration of use) or sponsors become aware of any issues that 
may impact the status of a technical section or the application, sponsors should contact 
their ONADE project manager for an NADA or the Division of Generic Animal Drugs 
for an ANADA.  CVM will make a decision on the impact this information has on the 
technical section or application. 
 
To avoid potential delay in the review of phased review data submissions related to the various 
technical sections, these submissions should be directed to the appropriate review division as 
provided in the following table. 
 
   
5  Contains Nonbinding Recommendations 
 
Technical Sections  Review Divisions 
Effectiveness,  Based on the intended uses for the new animal 
Target Animal Safety (including  drug, either to: 
user safety),   
Labeling, and  Division of Therapeutic Drugs for Non-Food 
All Other Information  Animals, 
Division of Production Drugs, or 
Division of Therapeutic Drugs for Food Animals 
Bioequivalence,  Division of Generic Animal Drugs 
Patent and Marketing 
Exclusivity, and Labeling 
Chemistry, Manufacturing, and  Division of Manufacturing Technologies 
Controls 
Human Food Safety  Division of Human Food Safety 
(Toxicology, Residue 
Chemistry, and Microbial Food 
Safety) 
Environmental Impact  Division of Scientific Support 
 
The review division will notify the sponsor in writing of its conclusions on acceptance or non-
acceptance of the data submitted relevant to a technical section.  If the review division finds the 
data for the technical section to be complete and the requirements for the technical section to be 
met, the division will issue a technical section complete letter.  A final decision on the approval 
of an application will be made when the administrative (A)NADA is submitted and CVM 
evaluates whether all the data for all technical sections, when viewed as a whole, continue to 
support approval. 
 
Any person intending to file an application for a new animal drug approval, i.e., an (A)NADA, 
or a request for an investigational exemption under section 512(j) of the FD&C Act is 
encouraged to request one or more presubmission conferences with CVM early in the drug 
development process and before making such submission.  One purpose of such a meeting would 
be to reach an agreement acceptable to CVM regarding the submissions or investigations 
necessary to meet the requirements for an approval (see 21 CFR 514.1). 
 
Coordinating the submission of technical sections remains the responsibility of the drug sponsor.  
There are obvious and varying degrees of interdependence among the technical sections, e.g., 
concerns about target animal safety may place boundaries on the dose(s) evaluated in drug 
effectiveness studies.  Because these interdependencies may exist, individual drugs under 
development may benefit from particular and unique timings and orderings for the submission of 
technical sections.  Therefore, CVM encourages sponsors to use the presubmission conference 
process to discuss these details. 
 
Before submission of the (A)NADA (whether administrative in nature or not), the sponsor is 
responsible for ensuring all necessary technical sections are complete, compatible, and support 
the approval of the same drug product.  If the sponsor chooses to progress from a phased review 
6  Contains Nonbinding Recommendations 
approach to the filing of the (A)NADA, and this does not result in an approval, subsequent 
submissions for the application must be made to the (A)NADA and not to the (J)INAD. 
 
V.  DESCRIPTIONS OF THE TECHNICAL SECTIONS 
 
A.  For pioneer applications 
 
There are seven technical sections for an NADA:  Chemistry, Manufacturing, and 
Controls; Effectiveness; Target Animal Safety; Human Food Safety; Environmental 
Impact; Labeling; and All Other Information.  Discussions with the appropriate review 
divisions will be necessary to determine which technical sections are required to support 
a specific approval.  Each of the technical sections is described in detail in 21 CFR 
514.1.  A brief synopsis of each is presented below. 
 
1.  Chemistry, Manufacturing, and Controls 
 
This section contains complete information regarding the manufacture of the new 
animal drug active ingredient and the new animal drug product.  It includes 
information on personnel, facilities, components and composition, manufacturing 
procedures, analytical specifications and methods, control procedures, stability, 
containers and closures, Good Manufacturing Practice (GMP) compliance, and many 
other aspects of the chemistry and manufacturing processes (21 CFR 514.1(b)(4) and 
(5)). 
 
2.  Effectiveness 
 
This section contains full reports of all studies that show whether or not the new 
animal drug is effective for its intended use (21 CFR 514.1(b)(8)(i)).  This section 
includes studies conducted by or on behalf of the sponsor or available to the sponsor 
by right of reference.  References and authorizations, if appropriate, to other 
applications or documents containing information regarding effectiveness of the new 
animal drug should also be included in this section of the application.  Section 
512(d)(1)(E) of the FD& C Act (21 USC  360b(d)(1)(E)) provides that CVM must 
refuse to approve an NADA unless the sponsor demonstrates by substantial evidence 
that the drug will have the effect it purports or is represented to have under the 
conditions of use prescribed, recommended, or suggested in the proposed labeling.  
This section includes any additional pertinent information that is known about the 
effectiveness of the drug at the time the technical section is submitted. 
 
3.  Target Animal Safety 
 
This section contains full reports of all studies required by FDA to demonstrate 
whether or not the new animal drug is safe to the target species (21 CFR 
514.1(b)(8)(i)).  All studies should include those studies conducted by or on behalf of 
the sponsor or that are available to the sponsor by right of reference.  References and 
authorizations, if appropriate, to other applications or documents containing 
7  Contains Nonbinding Recommendations 
information regarding safety of the new animal drug should also be included in this 
section of the application.  This section also contains any studies or references 
relevant to the safety of humans that administer or may come into direct contact with 
the new animal drug (user safety).  This section includes any additional pertinent 
information that is known about the target animal safety of the drug at the time the 
technical section is submitted. 
 
4.  Human Food Safety 
 
This section is submitted only for applications for new animal drugs intended for use 
in species that are used for human food (food-producing animals).  This section 
includes a description of practicable methods for determining the quantity, if any, of 
the new animal drug in or on food, and any substance formed in or on food because of 
its use, and the proposed tolerance or withdrawal period or other use restrictions to 
ensure that the proposed use of the drug will be safe (21 CFR 514.1(b)(7)).  This 
section should also contain any data relating to residue toxicology (including the 
impact of residues of antimicrobials on human intestinal microflora), residue 
chemistry, and, if the new animal drug is an antimicrobial, microbial food safety.  
This section includes any additional pertinent information that is known about the 
human food safety of the drug at the time the technical section is submitted. 
 
5.  Environmental Impact 
 
This section (21 CFR 514.1(b)(14)) contains either an environmental assessment 
(EA) under 21 CFR 25.40, or a request for categorical exclusion under 21 CFR 25.30 
or 25.33.  Under 21 CFR 25.15(a), a claim of categorical exclusion must include a 
statement of compliance with the categorical exclusion criteria and must state that to 
the sponsors knowledge, no extraordinary circumstances exist.  Environmental 
Impact Considerations and directions for preparing an EA can be found in 21 CFR 
Part 25. 
 
6.  Labeling 
 
This section (21 CFR 514.1(b)(3)) includes facsimile or final copies of container 
labels, package inserts, and all other labeling components that will be associated with 
the product.  For medicated feeds, copies of representative labeling for the Type B 
and Type C medicated feeds, often referred to as Blue Bird labeling, and a 
veterinary feed directive form, if required, should also be included.  Facsimile 
labeling is nearly final labeling that adequately reproduces the package size (actual or 
to scale); graphics; pictures; type size, font, and color of text; and, the substance of 
the text to demonstrate to the reviewing division that the final printed labeling will be 
in compliance with applicable regulations. 
   
8  Contains Nonbinding Recommendations 
 
7.  All Other Information (AOI) 
 
This section includes all other information, not included in any of the effectiveness, 
target animal safety, and/or human food safety technical sections, that is pertinent to 
an evaluation of the safety or effectiveness of the new animal drug for which approval 
is sought (21 CFR 514.1(b)(8)(iv)).  All other information includes, but is not limited 
to, any information derived from other marketing (domestic or foreign) and favorable 
and unfavorable reports in the scientific literature.  If there is no additional 
information that has not been previously submitted, the sponsors AOI technical 
section should contain a statement to that effect. 
 
B.  For generic applications 
 
There are six technical sections for an ANADA:  Bioequivalence; Patent and Marketing 
Exclusivity; Chemistry, Manufacturing, and Controls; Human Food Safety; 
Environmental Impact; and Labeling.  Discussions with the appropriate review divisions 
will be necessary to determine which technical sections are required to support a specific 
approval.  The descriptions for the technical sections for an ANADA are the same as 
those identified above for an NADA with the following exceptions. 
 
1.  Bioequivalence 
 
This section contains full reports of all studies that show the generic new animal drug 
is bioequivalent to the reference listed new animal drug or all information submitted 
in support of a waiver from the requirement to demonstrate in-vivo bioequivalence.  
All studies should include those studies conducted by, or on behalf of, the sponsor or 
available to the sponsor by right of reference. 
 
2.  Human Food Safety 
 
In the instances where human food safety information is required, the division 
responsible for the evaluation of this information will advise the sponsor as to the 
requirements that must be met. 
 
3.  Patent and Marketing Exclusivity 
 
This section includes the appropriate patent certification or statement (see 21 CFR 
314.94(a)(12)).  It also contains an appropriate statement with regard to the current 
marketing exclusivity status of the reference listed new animal drug. 
 
VI.  SUBMITTING AN ADMINISTRATIVE (A)NADA 
 
When a sponsor has received technical section complete letters for all of the technical sections 
required to support approval of a new animal drug, the sponsor may file an administrative 
(A)NADA.  It is the responsibility of the sponsor to ensure that all technical sections of an 
9  Contains Nonbinding Recommendations 
application are complete and support the approval of the new animal drug application.  In those 
instances in which a collective review of the technical sections of the administrative NADA 
raises questions about the safety or effectiveness of the new animal drug, CVM will refuse to 
approve the application under section 512(d)(1) of the FD&C Act.  Likewise, when a collective 
review of the technical sections of the administrative ANADA raises significant questions about 
any requirement for approval of the ANADA, CVM will refuse to approve the application under 
section 512(c)(2)(A) of the FD&C Act.  CVM encourages sponsors to use presubmission 
conferences during their drug development and review process to minimize those occasions on 
which a review division may identify problems after the administrative (A)NADA has been 
submitted. 
 
An administrative (A)NADA can be submitted in paper or electronic format.  A paper 
submission of an administrative (A)NADA should include a cover letter, signed FDA Form 
356V, a table of contents, summary, a copy of each technical section complete letter, and 
complete facsimile or final printed labeling.  Address the cover letter for the application to the 
division director responsible for the evaluation of effectiveness or in the case of generics, the 
division responsible for the evaluation of bioequivalence.  Clearly identify at the top of the letter 
that the submission is an administrative (A)NADA.  If this is a paper submission, send it to 
CVMs Document Control Unit.  If the submission is electronic, send it to CVM using the 
eSubmitter tool and it will contain the equivalent information identified above once the 
submission process in eSubmitter is complete. 
 
It is important to note the AOI technical section expires 90 days after the date of the AOI 
technical section complete letter.  Therefore, a sponsor needs to submit their administrative 
NADA within 90 days of that date. 
 
VII.  TIME FRAME FOR REVIEW 
 
Section 512(c)(1) of the FD&C Act requires FDA to approve or not approve an application 
within 180 days, or within such additional period as FDA and the sponsor may agree upon, after 
the filing of an application.  The FD&C Act does not specify the order or timing for submission 
of data in support of an application.  If the data are submitted as part of the phased review 
process, CVM intends to consider the application filed when it receives the administrative 
application because it is at this point that the agency should have all the elements required by 21 
CFR 514.1. 
 
A.  Administrative NADA 
 
If an application is identified as an administrative NADA, CVM will assign the 
application a 60-day review time frame (or such other review time frame as contained in 
the current user fee Goals Letter).  The application will be forwarded to the director of 
the division responsible for the evaluation of effectiveness who will review the NADA 
to determine if it meets the definition of an administrative NADA.  If the application 
does not meet the definition, CVM intends to assign it the statutory 180-day time frame 
(or such other review time frame as identified in the current user fee Goals Letter) and 
notify the sponsor.  CVM intends to evaluate all NADAs within 30 days of receipt to 
10  Contains Nonbinding Recommendations 
determine whether any of the grounds to refuse to file the application under 21 CFR 
514.110 apply. 
 
The division responsible for the evaluation of effectiveness will review the information 
submitted as part of an administrative NADA to ensure that all the information necessary 
to make an approval decision has been provided, is complete, and is consistent when all 
the technical sections are considered together. 
 
B.  Administrative ANADA 
 
If an application is identified as an administrative ANADA, CVM will assign the 
application a 90-day review time frame (or such other review time frame as identified in 
the current user fee Goals Letter).  The application will be forwarded to the director of 
the Division of Generic Animal Drugs who will review the ANADA to determine if it 
meets the definition of an administrative ANADA.  If the application does not meet the 
definition, CVM intends to assign it the statutory 180-day time frame (or such other 
review time frame as identified in the current user fee Goals Letter) and notify the 
sponsor.  CVM intends to evaluate all ANADAs within 30 days of receipt to determine 
whether any of the grounds to refuse to file the application under 21 CFR 514.110 apply. 
 
The Division of Generic Animal Drugs will review the information submitted as part of 
an administrative ANADA to ensure that all the information necessary to make an 
approval decision has been provided, is complete, and is consistent when all the 
technical sections are considered together. 
 
VIII.  PATENT TERM RESTORATION ISSUES 
 
Under U.S. patent law (35 U.S.C.  156(a)), the term of a patent for a new animal drug or its 
method of use may be extended if it meets certain criteria, one of which is that it was subject to a 
regulatory review period before its commercial marketing or use.  While there are other 
important criteria that must be met, a full discussion of the issues relating to patent term 
extension is beyond the scope of this guidance. 
 
In summary, however, the regulatory review period is divided into two time periods.  The first 
period (sometimes called the investigational period) begins when the sponsor submits a request 
to CVM to establish an INAD file, or when a major health or environmental effects test is 
initiated, and ends when an NADA is submitted.  The second period (the approval period) begins 
with submission of the NADA and ends when the application is approved (35 U.S.C.  
156(g)(4)(B)).3  Subject to certain important limitations, a patent may be extended for a time 
roughly equal to the second time period plus one half the first time period (35 U.S.C.  
156(c)(2)).  Because FDA intends that the time it takes to approve an application that qualifies as 
an administrative NADA usually will be shorter than the time it takes to approve a non-
administrative or traditional NADA, a new animal drug that was the subject of an administrative 
                                                 
3 See Wyeth Holdings Corp. v. Sebelius, 603 F.3d 1291, 1299 (Fed. Cir. 2010) (holding that an application is initially 
submitted with respect to the approval phase under 35 U.S.C.  156(g) when a sponsor submits an administrative NADA to the 
agency). 
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NADA is likely, in most cases, to receive a shorter patent term extension than it would have 
received had it been the subject of the non-administrative (traditional) NADA review and 
approval process. 
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