Information Requests 
and Discipline Review 
Letters Under GDUFA  
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
October 2022 
Generic Drugs 
 
Revision 1 
   
Information Requests 
and Discipline Review 
Letters Under GDUFA  
Guidance for Industry 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov   
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
and/or 
 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research  
Food and Drug Administration  
10903 New Hampshire Ave., Bldg. 71, Room 3128  
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010  
Email: ocod@fda.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
October 2022 
Generic Drugs 
 
Revision 1 
  Contains Nonbinding Recommendations  
 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  EXPLANATION OF TERMS AND PHRASES ............................................................ 3 
IV.  ISSUANCE AND USE OF INFORMATION REQUESTS AND DISCIPLINE 
REVIEW LETTERS ........................................................................................................ 4 
A.  General Information ...................................................................................................................... 4 
B.  Information Request and Discipline Review Letters and Applicant Responses ...................... 5 
  Contains Nonbinding Recommendations 
 
Information Requests and Discipline Review Letters Under GDUFA 
Guidance for Industry1 
 
 
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 office responsible for this guidance as listed on the title 
page. 
 
 
 
I.  INTRODUCTION  
 
This guidance explains how FDA will issue and use an information request (IR) and/or a 
discipline review letter (DRL) during the assessment2 of an original abbreviated new drug 
application (ANDA) under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 355(j)), as contemplated in the GDUFA Reauthorization Performance Goals and 
Program Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter).3  This 
guidance does not apply to a supplement or an amendment to a supplement. 
 
Under the Generic Drug User Fee Amendments of 2012 (GDUFA I), FDA committed to 
performance goals for acting on received ANDAs.4  FDA also committed to performance goals 
for acting on received ANDAs in the GDUFA Reauthorization Performance Goals and Program 
Enhancements Fiscal Years 2018-2022 (GDUFA II commitment letter) and the GDUFA III 
commitment letter.  In addition to these performance goals, FDA committed in the GDUFA II 
commitment letter and the GDUFA III commitment letter to provide applicants preliminary 
thoughts on possible deficiencies as each assessment discipline finishes its initial assessment of 
its portion of the received application (except when that assessment results in the ability to act on 
such application).  
 
This guidance revises the guidance of the same title issued in January 2022.  This revision is 
being issued to incorporate information on IRs and DRLs included in the GDUFA III 
 
1 This guidance has been prepared by the Office of Generic Drugs and the Office of Pharmaceutical Quality in the 
Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research at the Food and 
Drug Administration.  You may submit comments on this guidance at any time.  Submit comments to Docket No. 
FDA-2017-D-6752 (available at https://www.regulations.gov/docket/FDA-2017-D-6752).    
2 The Office of Generic Drugs and the Office of Pharmaceutical Quality will generally use the term assessment in 
place of review.  See guidance for industry Good ANDA Submission Practices (January 2022).  We update 
guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA guidance web 
page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.    
3 The GDUFA III commitment letter is available at: https://www.fda.gov/media/153631/download. 
4 Title III of the Food and Drug Administration Safety and Innovation Act (FDASIA), Public Law 112-144.  
FDASIA includes GDUFA I, and by reference, the Generic Drug User Fee Act Program Performance Goals and 
Procedures (GDUFA I commitment letter).  Under 21 CFR 314.101(b)(1), an ANDA is received when FDA has 
made a threshold determination that the abbreviated application is substantially complete. 
  1  Contains Nonbinding Recommendations 
 
commitment letter, including FDAs issuance and use of IRs and DRLs and identification of 
major and minor deficiencies.    
 
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 guidance means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
The Generic Drug User Fee Amendments of 2012 (GDUFA I)5 amended the FD&C Act to 
authorize FDA to assess and collect user fees to provide FDA with resources6 to help ensure 
patients have access to quality, affordable, safe, and effective generic drugs.  GDUFA fee 
resources bring greater predictability and timeliness to the review of generic drug applications.  
GDUFA has been reauthorized every 5 years to continue FDAs ability to assess and collect 
GDUFA fees, and this user fee program has been reauthorized two times since GDUFA I, most 
recently in the Generic Drug User Fee Amendments of 2022.  As described in the GDUFA III 
commitment letter applicable to this latest reauthorization, FDA has agreed to performance goals 
and program enhancements regarding aspects of the generic drug assessment program that build 
on previous authorizations of GDUFA.  New enhancements to the program are designed to 
maximize the efficiency and utility of each assessment cycle, with the intent of reducing the 
number of assessment cycles for ANDAs and facilitating timely access to generic medicines for 
American patients.  
 
Under the GDUFA III commitment letter, FDA agreed to issue IRs and/or DRLs for all 
ANDAs.7  As described in the GDUFA III commitment letter, FDA agreed to (1) issue an IR to 
request further information or clarification that is needed or would be helpful to allow 
completion of a discipline assessment and/or (2) issue a DRL, to convey preliminary thoughts on 
possible deficiencies found by a discipline assessor and/or assessment team for its portion of the 
application under assessment at the conclusion of a discipline assessment.8 
 
FDA strongly encourages applicants to submit high quality, complete applications.  Generally, 
the number and magnitude of deficiencies that FDA identifies in an application correlate to the 
number of assessment cycles.  Application quality and applicant responsiveness are key factors 
in whether IRs and DRLs have maximized value for a particular application. 
 
 
 
5 See footnote 4.  
6 User fees are available for obligation in accordance with appropriations acts. 
7 See the GDUFA III commitment letter at 12.  This commitment does not apply to an amendment made in response 
to a complete response letter (CRL), a supplement, or an amendment to a supplement.     
8 See GDUFA III commitment letter at 47.  If a discipline has not found any deficiencies by the mid-point of the first 
assessment cycle, FDA will also issue a DRL that states after preliminary assessment, that particular discipline has 
not identified deficiencies at the current time.  FDA issues these DRLs to promote transparency and communication 
between FDA and ANDA applicants.   
  2  Contains Nonbinding Recommendations 
 
III.  EXPLANATION OF TERMS AND PHRASES 
 
Acting on a received ANDA means the issuance by FDA of a CRL, an approval, or a tentative 
approval.9  A CRL, an approval, or a tentative approval will be issued after the complete 
assessment of a received ANDA by all appropriate disciplines.  If FDA issues a CRL, the CRL 
will set forth the deficiencies that an applicant must satisfactorily address before the ANDA can 
be tentatively approved or approved.  A CRL may contain additional or fewer deficiencies than 
were provided in previously issued DRLs, depending on the final assessment of the ANDA and 
concurrence by the appropriate signatory authority.10  Acting on a received ANDA completes the 
assessment cycle for that ANDA, which is the benchmark by which the Agency's performance 
towards GDUFA ANDA assessment goals is measured.  
 
A discipline assessment refers to FDAs assessment of the section of the ANDA pertaining to a 
certain discipline by its assessment staff (i.e., assessors) with expertise in that particular 
discipline.  These sections include, but are not limited to, the bioequivalence section, quality 
section, and labeling section of an ANDA.   
 
As defined in section II of this guidance, a DRL is a letter used to convey FDAs preliminary 
thoughts on possible deficiencies found by a discipline assessor and/or assessment team for its 
portion of the received ANDA at the conclusion of that disciplines assessment.  An assessment 
has reached its conclusion for these purposes when, at a minimum, the primary assessor of a 
discipline has read the relevant sections of the ANDA and developed preliminary thoughts on 
possible deficiencies.   
 
FDA does not consider DRLs to be CRLs because DRLs do not represent a complete assessment 
of the entire application and therefore do not stop the assessment clock.  In addition, a DRL does 
not necessarily reflect input from all supervisory levels.11  A single DRL may or may not contain 
comments from multiple discipline assessors.  If a discipline assessment team finds no 
deficiencies in its portion of the received ANDA, FDA will issue a DRL for that particular 
discipline that preliminarily indicates that no deficiencies have been identified at the completion 
of that assessment. 
 
Also as mentioned in section II of this guidance, an IR is a letter sent to an applicant during an 
application assessment to request further information or a clarification of the information already 
provided that is needed or would be helpful to allow completion of the discipline assessment.  
FDA does not consider IRs to be CRLs because IRs, like DRLs, do not represent a complete 
assessment of the entire application and therefore do not stop the assessment clock.  As with 
DRLs, an IR does not necessarily reflect input from all supervisory levels.  However, unlike 
DRLs, FDA may issue IRs before the completion of a discipline assessment.  
 
 
9 See GDUFA III commitment letter at 45.  
10 Signatory authority means an agency employee with the power to commit the Agency to an action on a particular 
ANDA.  
11 The phrase supervisory levels includes, but is not limited to, the appropriate signatory authority for the CRL.  
  3  Contains Nonbinding Recommendations 
 
IV.  ISSUANCE AND USE OF INFORMATION REQUESTS AND DISCIPLINE 
REVIEW LETTERS 
 
A.  General Information 
 
By the mid-point of the assessment clock of the first assessment cycle, FDA agreed to send an IR 
and/or a DRL to the applicant,12 except when a discipline assessment results in the ability to act 
on a received ANDA.13,14   The IR or DRL will identify whether the IR or DRL contains minor or 
major deficiencies.15  
 
FDA generally will use IRs to request further information or a clarification of the information 
that is needed or would be helpful to allow completion of a discipline assessment.  FDA will 
generally convey preliminary thoughts on possible deficiencies to applicants in the form of a 
DRL as each discipline finishes the assessment of available information in its section of the 
pending application, except when the discipline assessment results in the ability to act on a 
received ANDA.  
 
FDA will not issue a DRL if its issuance would delay or coincide with the issuance of a CRL.  
Applicants should not construe either the absence of a DRL for a particular discipline or a DRL 
for a particular discipline with no identified deficiencies to mean that the CRL will not contain 
any deficiencies for that discipline.  Comments in a DRL will usually reflect the input of the 
assessment team but not the input from all supervisory levels.  
 
The DRL will allow applicants to know as soon as possible the assessment team's preliminary 
thoughts on possible deficiencies that have been identified within specific sections of the 
application.  With this information, applicants can begin to assemble the needed data to address 
these deficiencies.  A DRL will pertain to only items that the assessment team believes may 
require resolution prior to full (or tentative) approval of the application.  A DRL is intended to 
convey preliminary thoughts on possible deficiencies found during a discipline assessment, 
whereas an IR is a request for further information or clarification that is needed or would be 
helpful to proceed with the discipline assessment.  
 
Applicants should be aware that because the DRL will originate at the discipline assessment 
team level and does not necessarily reflect input from all supervisory levels, a subsequent CRL, 
 
12 This commitment does not apply to IRs and DRLs issued by the labeling discipline, as described in Section 
II(B)(2)(a)(ii) of the GDUFA III commitment letter. 
13 If, upon initial submission, a standard or priority original ANDA contains a certification that a site/facility listed 
on the Form FDA 356h is not ready for inspection, FDA will not commence substantive assessment of the 
application until an amendment described in GDUFA III commitment letter subsection I(A)(3)(a) is submitted, and 
the mid-point of the assessment cycle will be determined upon receipt of this amendment and IRs or DRLs will be 
issued accordingly.  FDA will not issue a DRL until the mid-point of the period that begins with receipt of this 
amendment or the mid-point of the additional 15 months if the facility is still not ready after the initial 15-month 
period (see the GDUFA III commitment letter at 5). 
14 FDA may issue an IR prior to the mid-point of the assessment clock.   
15 GDUFA III commitment letter at 12.  Identification of major or minor deficiencies will be determined as noted in 
the guidance for industry ANDA Submissions  Amendments to Abbreviated New Drug Applications Under 
GDUFA (July 2018).   
  4  Contains Nonbinding Recommendations 
 
if issued, may contain more or fewer deficiencies than were provided in previously issued DRLs, 
depending on the final assessment and concurrence by the appropriate signatory authority.  In 
addition, as assessments from different disciplines (and internal consults) are integrated, 
additional concerns might arise or previously stated concerns may be resolved.  Therefore, it is 
possible that information requested in the DRL may be gathered by an applicant, but that in the 
end, such information may not be necessary for responding to a CRL, if issued.  
 
DRLs and IRs generally will contain a requested response date; if so, the response date will be 
determined by the discipline assessment team issuing the DRL or IR.  FDA generally expects 
that the applicant will respond to a DRL or IR by the requested response date or as quickly as 
possible.  However, applicants may request a short extension of time if they are unable to 
respond by the requested response date.16  If an IR or DRL does not contain a requested response 
date, it generally indicates that the discipline does not anticipate assessing any response to the IR 
or DRL during the current assessment cycle due to the nature of the request or deficiency and 
likely signifies a forthcoming CRL.17   
 
Applicants that are eligible to request a mid-cycle review meeting (MCRM) or an enhanced mid-
cycle review meeting (EMCRM) may, within 7 days of receiving the last mid-cycle DRL (the 
latter of the quality DRL and the bioequivalence or clinical bioequivalence DRL), submit a 
request for either an MCRM or an EMCRM.18   
 
B.  Information Request and Discipline Review Letters and Applicant Responses  
 
In the first assessment cycle, FDAs issuance of an IR or a DRL and the applicants response 
may affect the goal date.  For an IR or DRL issued by the mid-point of the assessment, if the 
applicant responds by the response due date, FDA agreed to assess a response to minor 
deficiencies within the originally assigned goal date for the submission.19  However, applicant 
responses to an IR or DRL issued by the mid-point of the assessment containing any major 
deficiencies, or minor deficiencies if the responses include data and information that require 
comparable FDA assessment resources to those require for major deficiencies (e.g., consults), 
will be considered major amendments.  FDA will extend the goal date consistent with the 
number of months needed to assess a comparable standard or priority Major Amendment.20  
 
For IRs and DRLs issued after the mid-point of the first assessment cycle, the assessment 
discipline generally will assign a due date for the response and identify whether the IR or DRL 
contains minor or major deficiencies.21 
 
 
16 Extensions will be granted by FDA in only exceptional circumstances.  Applicants should make a request for an 
extension as soon as they become aware of the exceptional circumstance. 
17 GDUFA III commitment letter at 13.   
18 For more information on MCRMs and EMCRMs, see the guidance for industry Formal Meetings Between FDA 
and ANDA Applicants of Complex Products Under GDUFA (October 2022).     
19 GDUFA III commitment letter at 12.  Exceptions that apply to the Labeling discipline are described in Section 
II(B)(1)(iii) of the GDUFA III commitment letter. 
20 GDUFA III commitment letter at 13.  FDAs decision to extend the goal date will be communicated in an 
amendment acknowledgement letter. 
21 GDUFA III commitment letter at 13.  
  5  Contains Nonbinding Recommendations 
 
FDA agreed to issue IRs and DRLs after the mid-point of the first assessment cycle and at any 
time in subsequent assessment cycles, when, in FDAs judgment, there are one or more minor 
deficiencies in a discipline that, if resolved using an IR or DRL, could lead to approval or 
tentative approval of an ANDA in the current assessment cycle.22  FDA agreed to issue the IR or 
DRL and provide a due date for the applicants response before the goal date.23  If the applicant 
responds to the minor deficiencies in the IR or DRL by the due date (or any agreed-upon 
extension), and FDA finds the amendment to satisfactorily address all of the issues identified in 
the IR or DRL, and the response does not contain unsolicited information, FDA may extend the 
goal date by 90 days from the date of the applicants response.24  
 
FDA agreed to continue to issue IRs and/or DRLs late in the assessment cycle for original 
submissions and amendments until it is no longer feasible within the current assessment cycle for 
the applicant to develop and FDA to assess a response to the IR and/or DRL.25   
 
If a response to an IR or a DRL contains either information not requested by FDA or information 
that requires a more thorough assessment (e.g., the assessor issues a consult to another 
discipline) as determined by FDA, FDA will classify the submission as an amendment and 
assign an appropriate new goal date for that amendment.26   
 
Furthermore, if the Agency determines that it cannot assess a response before the goal date or if a 
CRL is otherwise ready to be issued, the assessment of the IR or DRL response may, in general, 
be deferred.27  When FDA defers the assessment of a response to an IR or DRL, the response 
will be assessed during the next assessment cycle for the application as part of the CRL 
amendment and this will be communicated in the CRL.   
 
If the applicant does not provide a complete response to an IR and/or DRL by the response due 
date (or any agreed-upon extension), FDA may include the same deficiencies from the IR or 
DRL in a CRL and assess the response during the next assessment cycle.28  
 
Deficiencies addressed by applicants in a response to an IR or a DRL may appear in a CRL if 
FDAs assessment of the response has been deferred or if FDA has outstanding concerns after 
assessment of the response.  The CRL will include all deficiencies that must be satisfactorily 
addressed before the ANDA can be approved. 
 
If the applicant receives a CRL but has responded to some (or all) identified deficiencies in an IR 
or DRL response, the applicant does not need to re-submit previously submitted information in a 
CRL amendment.  However, the applicant should still submit a CRL amendment and should 
 
22 Ibid.    
23 Ibid.  
24 Ibid.  See also footnote 20.    
25 GDUFA III commitment letter at 13.  
26 See the guidance for industry ANDA Submissions  Amendments to Abbreviated New Drug Applications Under 
GDUFA (July 2018). 
27 FDA will continue assessment of an ANDA past the goal date if, in FDAs judgment, it may be possible to 
approve or tentatively approve an ANDA within 60 days after the goal date (GDUFA III commitment letter at 14).   
28 GDUFA III commitment letter at 13.  
  6  Contains Nonbinding Recommendations 
 
clearly identify the previously provided IR or DRL response that renders its CRL amendment 
complete. 
  7