Cover Letter 
Attachments for 
Controlled 
Correspondence and 
ANDA Submissions 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
June 2023 
Generic Drugs 
  Cover Letter 
Attachments for 
Controlled 
Correspondence and 
ANDA Submissions 
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  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 
June 2023 
Generic Drugs      Contains Nonbinding Recommendations     
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  USING THE COVER LETTER ATTACHMENTS ..................................................... 3 
APPENDIX 1: COVER LETTER ATTACHMENT FOR CONTROLLED 
CORRESPONDENCE ................................................................................................................. 4 
APPENDIX 2: COVER LETTER ATTACHMENT FOR ORIGINAL ANDAS, 
AMENDMENTS TO ORIGINAL ANDAS, AND GENERAL CORRESPONDENCE 
RELATED TO ORIGINAL APPLICATIONS.......................................................................... 7 
APPENDIX 3: COVER LETTER ATTACHMENT FOR SUPPLEMENTS TO 
APPROVED ANDAS, AMENDMENTS TO PENDING SUPPLEMENTS, 
AMENDMENTS TO TENTATIVELY APPROVED PEPFAR ANDAS, AND GENERAL 
CORRESPONDENCE RELATED TO THESE SUBMISSIONS .......................................... 13 
  Contains Nonbinding Recommendations 
Cover Letter Attachments for Controlled Correspondence and 
ANDA Submissions  
Guidance for Industry1
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or the 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 is intended to assist prospective applicants, applicants, and holders of abbreviated 
new drug applications (ANDAs) with optional attachments that can be used when preparing 
cover letters that accompany controlled correspondence,2 original ANDAs, amendments to 
ANDAs, and supplements to approved ANDAs submitted to FDA.  These attachments do not 
replace the recommendations for the content of cover letters provided in other FDA guidances.3 
 
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 Generic Drug User Fee Amendments of 2012 (GDUFA I)4 amended the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) to authorize FDA to assess and collect user fees to provide the 
 
1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug Evaluation and Research at 
the Food and Drug Administration.  
2 Controlled correspondence is correspondence submitted to the Agency, by or on behalf of a generic drug 
manufacturer or related industry, requesting information on a specific element of generic drug product development.  
See GDUFA Reauthorization Performance Goals and Program Enhancements fiscal years (FYs) 2023-2027 
commitment letter (GDUFA III Commitment Letter), available at https://www.fda.gov/media/153631/download.  
See also the guidance for industry Controlled Correspondence Related to Generic Drug Development (December 
2020).  We update guidance periodically.  For 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 Recommended content of cover letters (or first page of submission) is provided in the following guidances for 
industry: Controlled Correspondence Related to Generic Drug Development (December 2020); ANDA 
SubmissionsContent and Format (June 2019); ANDA SubmissionsAmendments to Abbreviated New Drug 
Applications Under GDUFA (July 2018); and ANDA SubmissionsPrior Approval Supplements Under GDUFA 
(October 2017).   
4 Generic Drug User Fee Amendments of 2012, Title III of the Food and Drug Administration Safety and Innovation 
Act (Public Law 112-144, Title III). 
  1  Contains Nonbinding Recommendations 
Agency with resources5 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 Continuing Appropriations and 
Ukraine Supplemental Appropriations Act, 2023.6  As described in the GDUFA III commitment 
letter applicable to this latest reauthorization,7 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.  
 
The enhancements described in the GDUFA III commitment letter include expansion of the 
types of correspondence that can be submitted as controlled correspondence,8 as well as other 
submission and communication enhancements designed to improve the efficiency of ANDA 
assessment.  The recommendations in this guidance are intended to aid applicants in preparing 
cover letters for controlled correspondence and common ANDA submissions to help ensure 
these cover letters include pertinent information to aid FDAs assessment of the submission.  A 
cover letter is generally included with controlled correspondence to the Office of Generic Drugs 
(OGD) and submissions to an ANDA file.  While a cover letter is not required content for an 
ANDA, the cover letter is a part of the electronic common technical document (eCTD) hierarchy 
and is included in Module 1 of an ANDA submission.9   
 
The cover letter provides an overview of the submission and helps FDA ensure that the 
submission is properly triaged and assigned to the appropriate assessors.  In an effort to ensure 
that submissions are effectively managed by FDA and acted upon within the performance review 
goal dates agreed to in the GDUFA III commitment letter, FDA has developed cover letter 
attachments to accompany, not replace, the applicants10 cover letter for the following common 
submissions: controlled correspondence, original ANDAs and amendments to ANDAs, and 
supplements to approved ANDAs.  Use of the cover letter attachments contained in the 
appendices of this guidance is voluntary, and the absence of a cover letter attachment in a 
submission would not be a basis for a submission to be considered deficient or for a refuse-to-
receive (RTR) determination.   
 
 
 
 
5 User fees are available for obligation in accordance with appropriations acts.  
6 See Division F, Title III of the Continuing Appropriations and Ukraine Supplemental Appropriations Act, 2023 
(Public Law 117-180). 
7 The GDUFA III commitment letter, available at https://www.fda.gov/media/153631/download. 
8 See GDUFA III commitment letter at 11. 
9 See The Comprehensive Table of Contents Headings and Hierarchy, available at 
https://www.fda.gov/media/76444/download. 
10 Use of the term applicant in this guidance includes prospective ANDA applicants, ANDA applicants, and ANDA 
holders. 
  2  Contains Nonbinding Recommendations 
III.  USING THE COVER LETTER ATTACHMENTS 
 
The cover letter attachments provided in this guidance have been developed by the divisions that 
receive and respond to controlled correspondence and that assess ANDAs (including 
amendments and supplements).  The cover letter attachments have been designed as a checklist 
to reflect common types of information applicants are expected to address in the cover letter for 
their submission.  Please note that these checklists are not an exhaustive list of the information 
needed from applicants for a particular submission.  There may be additional items that need to 
be submitted with a particular submission; for example, information related to patents and 
exclusivities may need to be submitted with some ANDA submissions. 
 
Prospective ANDA applicants, ANDA applicants, and ANDA holders may complete and submit 
the appropriate attachment(s) along with their cover letter.  Applicants are not required to submit 
an attachment with their cover letter; however, the optional cover letter attachment can be a 
useful guide to help applicants prepare their cover letters, particularly in situations covered in 
Appendices 2 and 3.  The format of the cover letter attachment may be adapted by the applicant 
for their convenience.  The main purpose of the cover letter attachment is to help applicants 
ensure that they are addressing relevant information in any cover letter submitted to FDA for the 
submissions covered in this guidance.  Completing a relevant checklist and attaching it to the 
cover letter submission is helpful to FDA in the triage of applications and management of 
submissions.   
 
The cover letter attachment provided in Appendix 1 of this guidance is intended for use with 
controlled correspondence submitted to OGD.  The cover letter attachment provided in Appendix 
2 of this guidance is intended for original ANDA submissions, amendments to original ANDAs, 
and any general correspondence associated with that original ANDA.  The cover letter 
attachment provided in Appendix 3 of this guidance is for supplements to approved ANDAs, 
amendments to pending supplements, submissions to tentatively approved ANDAs under the 
Presidents Emergency Plan for AIDS Relief (PEPFAR) program,11 and any general 
correspondence related to these submissions.   
 
11 Under PEPFAR, certain antiretroviral products that have been granted a tentative approval may be distributed for 
use outside of the United States, even when there is still patent and/or exclusivity protection in the United States.  
See FDAs PEPFAR web page, available at https://www.fda.gov/international-programs/presidents-emergency-
plan-aids-relief-pepfar. 
  3  Contains Nonbinding Recommendations 
APPENDIX 1: COVER LETTER ATTACHMENT FOR CONTROLLED 
CORRESPONDENCE 
 
Controlled Correspondence (CC) Background 
Submission Date   
Subject   
Person Submitting the CC 
Name   
Title   
Entity (e.g., corporate affiliation)   
Note here if this is a U.S. Agent, 
Prospective Applicant, or Applicant 
Address   
Phone number   
Email   
Relevant Reference Listed Drug (RLD)/Reference Standard (RS) Information 
Application number   
Proprietary (brand) name   
Manufacturer   
Established Name   
Dosage form   
Strength(s)   
CC Information 
Concise statement of the inquiry   
 
 
 
 
Applicant or prospective applicants   
recommendation of the appropriate FDA 
review discipline 
Additional Background  Yes  No or N/A 
Are copies of relevant prior research, background information,     
and supporting materials included with the CC submission? 
 
Drug-Device Combination Product  Yes  No or N/A 
Is the product or proposed product a drug-device combination     
product? 
 
Note: If this is a combination product, mark the corresponding 
box to identify it as such on line #24 of the FDA Form 356h. 
  4  Contains Nonbinding Recommendations 
 
Previous CC History 
  If this is related to a previous CC that was accepted for substantive review and response, 
provide the FDA-assigned CC number and submission date. 
  Include copies of all previous, related CC(s) accepted for substantive review and response and 
the Agencys response. 
Previous CC  Submission  Concise Statement of  Concise Statement of Agencys 
Number  Date  Inquiry  Response 
       
       
       
       
       
       
 
 
Related Submissions 
  If this is related to a submitted abbreviated new drug application (ANDA) or a pre-assigned 
ANDA, provide the information below. 
ANDA Number  Submission Date  Submission Status 
     
     
     
     
     
 
   
  5  Contains Nonbinding Recommendations 
 
Previous Meeting and PSG Teleconference (TCon) History 
  If this is related to a previous meeting and/or PSG TCon, provide the assigned ANDA number, 
meeting type, and meeting date. 
  Include copies of all previous, related meeting and PSG TCon requests and the Agencys 
response(s). 
ANDA Number  Meeting Type   Meeting Date 
     
     
     
     
     
     
 
List of attachments provided: 
 
1. 
2. 
3.   
  6  Contains Nonbinding Recommendations 
APPENDIX 2: COVER LETTER ATTACHMENT FOR ORIGINAL ANDAS, 
AMENDMENTS TO ORIGINAL ANDAS, AND GENERAL CORRESPONDENCE 
RELATED TO ORIGINAL APPLICATIONS12 
 
ANDA Background 
Abbreviated New Drug Application   
(ANDA) Number 
Applicant   
Submission Date   
Authorized Representatives Email   
Submission Type (e.g., Original,   
Amendment) 
Proposed Product Established Name   
Dosage Form   
Strength(s)   
Reference Listed Drug (RLD) (proprietary   
name (brand name), application number)  
Reference Standard (RS) (proprietary name   
(brand name), if any, established name, 
and application number) 
RLD/RS Application Number Used to   
Conduct Bioequivalence Studies 
Note: If priority review is being requested, please refer to the Agencys Manual of Policies and 
Procedures (MAPP) 5240.3 (Rev. 6), Prioritization of the Review of Original ANDAs, Amendments, 
and Supplements13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12 Note that there may be multiple submissions falling under this particular category related to a particular ANDA.  
Applicants should utilize the checklist for each specific submission and only include information relevant to the 
current submission, not previous submissions. 
13 The cover letter should clearly state Priority Review Requested; reference the ANDA number; provide the basis 
for the request, including the prioritization factor(s); and include sufficient supporting documentation for the 
request.  For additional information, see FDAs MAPP 5240.3 (Rev. 6), available at 
https://www.fda.gov/media/89061/download. 
  7  Contains Nonbinding Recommendations 
 
Select all applicable information included in the submission 
  Administrative General    Bioequivalence    Biopharmaceutics    Clinical 
Correspondence14 
  Scientific General 
Correspondence15 
  Drug Substance     Drug Product    Labeling    Microbiology 
(Drug Master File) DMF    Carve-out16 
#: __________________   Patent 
(Section viii 
statement)  
 Exclusivity 
 Dosage Form 
  Patent or    Pharm/Tox    Manufacturing:  
Exclusivity      Facility 
                               Active Pharmaceutical 
Ingredient (API) 
  Finished Dosage Form (FDF) 
(including packaging and 
labeling) 
  Testing 
  Request for 
  Other (e.g., storage, device 
Reconsideration 
constituent) 
  Ready for Inspection17 
  Process 
  Facility-Based Major CRL Amendment   
Request for Reclassification 
 
   
 
14 An administrative general correspondence is a general correspondence to FDA that does not include information 
required for review of the ANDA.  For example, it may include a change in the point of contact, applicant address, 
etc. 
15 A scientific general correspondence is a general correspondence from an applicant to FDA requesting scientific 
advice after a complete response letter has been issued by the Agency. 
16 Labeling carve-outs should be prominently identified (e.g., bolded) in the cover letter for these types of 
submissions. 
17 FDA recommends that applicants state in their cover letters Facility Ready For Inspection along with the 
ANDA number, if applicable. 
  8  Contains Nonbinding Recommendations 
 
Additional background  Yes  No or N/A 
1.  Is the email secure?       
If no, apply for a secure email with the FDA by contacting 
secureemail@fda.hhs.gov  
2.  Was a Pre-Submission Facility Correspondence (PFC) submitted?      
3.  If a PFC was submitted, have any significant changes been made to the     
pre-submitted facility information? 
4.  Does the submission contain any technology that has been accepted into or     
may qualify for the Emerging Technology Program18? 
5.  For all submissions: Was a Competitive Generic Therapy (CGT)     
designation granted for a drug product or drug products under this 
ANDA? 
6.  For original ANDAs:  Is a CGT designation request being made     
concurrently with the original ANDA submission?   
If yes, please refer to the guidance for industry Competitive Generic   
Therapies (March 2020) for additional information on what to include in   
the cover letter.19   
 
Drug-device combination product  Yes  No or N/A 
7.  Is the proposed product a drug-device combination product?     
If yes, answer questions #8 and #9. 
 
Note: If this is a combination product, mark the corresponding box to 
identify it as such on line #24 of the FDA Form 356h. 
8.  Does the submission include comparative analyses for a drug-device     
combination product?   
If yes, then specify location in the submission: __________________ 
 
9.  Does the submission include additional data and/or information, such as     
data from a comparative use human factors study, to support differences in   
user interface?   
If yes, then specify location(s) in the submission: 
__________________:__________________:__________________ 
 
18 See the guidance for industry Advancement of Emerging Technology Applications for Pharmaceutical Innovation 
and Modernization (September 2017). 
19 This guidance recommends including a statement supporting the request for designation and information 
supporting the assertion that there is inadequate generic competition for the drug product under section 506H of the 
FD&C Act (21 U.S.C. 356h). 
  9  Contains Nonbinding Recommendations 
Study Information  Yes  No or N/A 
10. Does the submission include an alternate method for demonstrating     
bioequivalence (BE) (e.g., modeling, in vitro testing) that deviates from 
the current recommendations in a Product-Specific Guidance? 
11. Does the submission include a request for a waiver under 21 CFR 320.22?      
            If yes and referencing a BE study submitted under a different  
             application, then include the original BE studys ANDA number,  
             submission date, and the module for the BE study referenced in 
             support of the waiver request in the current submission: 
_________________________________________ 
 
12. Are there any additional data and/or information from comparative studies     
(e.g., in vitro studies, failed BE studies) included in other modules besides 
module 5? 
If yes, then specify study type and location in the submission:  
__________________________________________________ 
_________________________________________________________ 
13. Does the submission include a Pharmacology/Toxicology (safety)     
justification, for example, nonclinical studies as defined in 21 CFR 
58.3(d)? 
If yes, then specify justification/study type and location in the submission:  
____________________________________________________________ 
 
 
Proposed product development history 
  For original ANDAs: ensure that copies of all related pre-ANDA communications accepted for 
substantive review and the Agencys response (e.g., controlled correspondence, pre-ANDA meeting 
written responses) are included in your submission 
  For subsequent amendments: only include updates or new information since last submission, as 
applicable 
Complete this section to document any prior FDA communications  Yes  No or N/A 
for this ANDA, as appropriate 
1.  Controlled correspondence(s)      
If yes, include #(s) and date(s): _______________________________ 
2.  Protocol review(s)     
If yes, include #(s) and date(s): _______________________________ 
3.  Bio-investigational new drug (Bio-IND) protocol review(s)     
If yes, include #(s) and date(s):  ______________________________ 
4.  Approved suitability petition for the basis of submission, as per 21     
CFR 314.94(a)(3)(iii) 
  10  Contains Nonbinding Recommendations 
If yes, include docket number and a copy of FDAs correspondence 
approving the petition:  _____________________________________ 
5.  Approved citizen petition requesting a specific basis of submission20     
If yes, include docket number:  _______________________________ 
6.  Pre-ANDA meeting(s)     
If yes, include #(s) and date(s):  ______________________________ 
7.  Scientific General Correspondence(s) after complete response letter     
(CRL) response (for amendments only) 
If yes, include #(s) and date(s):  ______________________________ 
8.  Device related communication(s) (for drug-device combination     
product only) 
If yes, include #(s) and date(s):  ______________________________ 
 
For Amendments Only 
Type of amendment  Date of FDA correspondence  Is this a response to a 
or action that elicited the  CRL?  
amendment (e.g., CRL, 
discipline review letter (DRL), 
Yes  No or N/A 
information request (IR), or 
tentative approval (TA) 
Unsolicited       
Solicited       
Post-TA amendment       
Post-TA Request for Final Approval       
Request For Reconsideration (RFR)       
Facility-Based Major CRL       
Amendment to Minor 
Reclassification Request  
Patent Certification/Statement  Yes  No21 
1.  Does the submission contain any of the following changes?     
 
(i) To add a new indication or other condition of use; 
(ii) To add a new strength; 
(iii) To make other than minor changes in product formulation; or 
 
20 See section III.C.3 in FDAs guidance for industry Referencing Approved Drug Products in ANDA Submissions 
(October 2020). 
21 N/A does not apply for Patent Certification/Statement. Under 21 CFR 314.96(d), an amendment to an 
unapproved ANDA must contain either (1) an appropriate patent certification or statement (or recertification), or (2) 
a verification that the proposed changes described in the amendment is not one of the types of amendments 
described in 21 CFR 314.96(d)(1). 
  11  Contains Nonbinding Recommendations 
(iv) To change the physical form or crystalline structure of the active 
ingredient 
 
If yes, please address this according to 21 CFR 314.96(d)(1) 
 
If no, please provide a statement according to 21 CFR 314.96(d)(2) 
within the cover letter 
Does the amendment submission include any of the following?  Yes  No or N/A 
2.  New strength (including new fill volume for parenteral products)     
3.  Modified formulation     
4.  New batch      
5.  Specification change(s)     
6.  New container closure system     
7.  Active Pharmaceutical Ingredient (API) source change     
If yes, then include Drug Master File (DMF) #: __________________ 
8.  Changes or additions to the manufacturing/quality facilities?     
9.  For a request for final approval, is new data being submitted?     
10. New bioequivalence (BE) study/studies      
If yes, then specify the following for each new BE study: 
a.  Select study type:  
in vivo or in vitro, including failed study 
b.  Study number: __________________ 
c.  Study site (clinical, analytical, in vitro testing)  
Name and address: 
______________________________________________ 
 
d.  Location of new BE study in the submission: 
_____________________________________ 
11. Updated labeling due to a new or revised patent or exclusivity     
currently listed in the Orange Book22 
   
 
22 The publication Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the 
Orange Book) identifies drug products approved on the basis of safety and effectiveness by FDA under the FD&C 
Act and related patent and exclusivity information.  For more information on the Orange Book, see the Agencys 
web page https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-
equivalence-evaluations-orange-book. 
  12  Contains Nonbinding Recommendations 
APPENDIX 3: COVER LETTER ATTACHMENT FOR SUPPLEMENTS TO 
APPROVED ANDAS, AMENDMENTS TO PENDING SUPPLEMENTS, 
AMENDMENTS TO TENTATIVELY APPROVED PEPFAR ANDAS, AND GENERAL 
CORRESPONDENCE RELATED TO THESE SUBMISSIONS23 
 
ANDA Background 
Abbreviated new drug application (ANDA)   
number 
Applicant   
Submission Date   
Email   
Established Name   
Dosage Form   
Strength(s)   
Reference Listed Drug (RLD) (proprietary   
name (brand name) and application 
number) 
Reference Standard (RS) (proprietary name   
(brand name), if any, established name, 
and application number) 
If priority review is being requested, please refer to FDAs Manual of Policies and Procedures 
(MAPP) 5240.3 (Rev. 6), Prioritization of the Review of Original ANDAs, Amendments, and 
Supplements24 
 
Select all applicable information included in the submission 
  Administrative General    Bioequivalence    Biopharmaceutics    Clinical 
Correspondence25     
  Scientific General 
Correspondence26 
 
23 Note that there may be multiple submissions falling under this particular category related to a particular ANDA.  
Applicants should utilize the checklist for each specific submission and only include information relevant to a 
particular application, not previous submissions. 
24 The cover letter should clearly state Priority Review Requested; reference the ANDA number; provide the basis 
for the request, including the prioritization factor(s); and include sufficient supporting documentation for the 
request.  For additional information, see FDAs MAPP 5240.3 (Rev. 6), available at 
https://www.fda.gov/media/89061/download. 
25 An administrative general correspondence is a general correspondence to FDA that does not include information 
required for review of the ANDA.  For example, it may include a change in the point of contact, applicant address, 
etc. 
26 A scientific general correspondence is a general correspondence from an applicant to FDA requesting scientific 
advice after a complete response letter has been issued by the Agency. 
  13  Contains Nonbinding Recommendations 
  Drug Substance     Drug Product    Labeling    Microbiology 
DMF #:    Carve-out27 
__________________    Patent 
  (Section 
viii 
statement)  
  Exclusivity 
  Dosage Form 
  Patent or    Pharm/Tox    Manufacturing:  
Exclusivity      Facility 
    Active Pharmaceutical 
Ingredient (API) 
  Request for 
  Finished Dosage Form 
Reconsideration 
(FDF) (including 
packaging/labeling) 
  Testing 
  Other (e.g., storage 
warehouse, device 
constituent parts) 
  Ready for Inspection28 
  Process 
  Facility-Based Major CRL Amendment   
Request for Reclassification 
 
  Notice of Commercial Marketing 
   
 
27 Labeling carve-outs should be prominently identified (e.g., bolded) in the cover letter for these types of 
supplements and amendments. 
28 FDA recommends that applicants state in their cover letters Facility Ready For Inspection along with the 
ANDA number, if applicable. 
  14  Contains Nonbinding Recommendations 
Additional Background  Yes  No or 
N/A 
1.  Is the email secure?      
If no, apply for a secure email with the FDA by contacting 
secureemail@fda.hhs.gov. 
2.  Was a Pre-Submission Facility Correspondence (PFC) submitted?      
3.  If a PFC was submitted, have any significant changes been made to     
the pre-submitted facility information? 
4.  Does the submission contain any technology that has been accepted     
into or may qualify for the Emerging Technology Program29? 
Drug-device combination product  Yes  No or 
N/A 
5.  Is the proposed product a drug-device combination product?     
If yes, answer questions #6 through #9. 
6.  Does the supplement propose a change to the drug-device combination     
product that may impact quality or labeling? 
7.  Does the supplement propose a change to the drug-device combination     
product that may impact the user interface? 
8.  Does the submission include comparative analyses for a drug-device     
combination product?   
If yes, then specify location in the submission:  _________________ 
 
9.  Does the submission include additional data and/or information, such     
as data from a comparative use human factors study, to support 
differences in user interface?   
If yes, then specify location(s) in the submission:  _______________ 
 
Does the submission (supplement or amendment to the supplement)  Yes  No or 
include any of the following?  N/A 
10. New strength (including new fill volume for parenteral products)     
11. Modified formulation     
12. Specification change(s)     
13. New container closure system     
 
29 See the guidance for industry Advancement of Emerging Technology Applications for Pharmaceutical Innovation 
and Modernization (September 2017). 
  15  Contains Nonbinding Recommendations 
14. Request for a Prescription (Rx) to over-the-counter (OTC) switch     
15. A reactivation/reintroduction request as noted in MAPP 5200.7 (Rev.     
1)30 
16. Revised and/or new patent certification and/or exclusivity statement     
17. Updated labeling due to a new or revised patent or exclusivity     
currently listed in the Orange Book 
18. A new facility that has never been inspected for similar operations to     
those proposed in the supplement 
19. Removal of a facility     
20. Active Pharmaceutical Ingredient (API) source change     
If yes, then include Drug Master File (DMF) #: __________________ 
21. A Pharmacology/Toxicology (safety) justification for example     
nonclinical studies as defined in 21 CFR 58.3(d)   
If yes, then specify justification/study type and location in the 
submission: __________________ 
 
22. New bioequivalence (BE) study/studies     
If yes, then specify the following for each new BE study: 
a.  Select Study type: in vivo or in vitro, including failed study 
b.  Study Number: __________________ 
c.  Study Site (clinical, analytical, in-vitro testing) Name and 
Address: __________________ 
d.  Location of new BE study in the submission: 
__________________ 
23. An alternate method for demonstrating BE (e.g., modeling, in vitro     
testing) that deviates from the current recommendations in a Product-
Specific Guidance 
24. A waiver request under 21 CFR 320.22?      
 
If yes, include the module where your waiver is located:  __________ 
 
 
Select one filing category corresponding to the highest risk of all proposed supplemental 
changes, ranked by supplement filing category (PAS, CBE-30, CBE-0) per 21 CFR 314.70 
  PAS    CBE-30    CBE-0 
 
 
30 FDAs MAPP 5200.7 (Rev. 1), ANDA Amendments and Supplements Reviewed by the Division of Filing Review, 
is available at https://www.fda.gov/media/94417/download. 
  16  Contains Nonbinding Recommendations 
 
 
For Amendments Only 
Type of amendment  Supplement #  Date of FDA  Is this a response to a 
correspondence or  CRL?  
action that elicited the 
amendment (e.g., 
Yes  No or 
Complete Response 
N/A 
Letter (CRL), discipline 
review letter (DRL), 
information request 
(IR), or tentative 
approval (TA)): 
 
Unsolicited         
Solicited         
Presidents Emergency         
Plan for AIDS Relief 
Program (PEPFAR) Post-
TA31 
Request for         
Reconsideration (RFR) 
Facility-Based Major         
CRL Amendment 
Reclassification Request 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
31 Under PEPFAR, certain antiretroviral products that have been granted a tentative approval may be distributed for 
use outside of the United States, even when there is still patent and/or exclusivity protection in the United States.  
See FDAs PEPFAR web page, available at https://www.fda.gov/international-programs/presidents-emergency-
plan-aids-relief-pepfar. 
  17  Contains Nonbinding Recommendations 
 
 
Proposed Changes 
  For all supplemental changes proposed, populate the table below, ranked by supplement filing 
category (PAS, CBE-30, CBE-0) per 21 CFR 314.70 
#  Change  Filing  Scale-Up and Post Approval  Justification for filing category 
description  category  Changes (SUPAC) level (1,  based on current guidances and/or 
2 or 3), as applicable32   risk assessment 
 
If the same change has been 
previously approved, include 
ANDA # and approval date for the 
same change. 
1         
 
2         
 
3         
 
4         
 
5         
 
 
 
32 SUPAC guidances are available for modified-release solid oral dosage forms, immediate-release solid oral dosage 
forms, and nonsterile semisolid dosage form products (see the guidances for industry SUPAC-MR: Modified Release 
Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro 
Dissolution Testing and In Vivo Bioequivalence Documentation (October 1997); SUPAC-IR: Immediate-Release 
Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro 
Dissolution Testing, and In Vivo Bioequivalence Documentation (November 1995); and SUPAC-SS: Nonsterile 
Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro 
Release Testing and In Vivo Bioequivalence Documentation (May 1997)).  These guidances define levels of change 
(i.e., SUPAC levels 1, 2, and 3) for the covered products, along with recommended tests and documentation that 
should support the change. 
  18