Submission of Controlled Correspondence

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, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s 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
Submissions—Content and Format (June 2019); ANDA Submissions—Amendments to Abbreviated New Drug
Applications Under GDUFA (July 2018); and ANDA Submissions—Prior 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).

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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
FDA’s 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 FDA’s 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 applicant’s10 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-toreceive (RTR) determination.

5

User fees are available for obligation in accordance with appropriations acts.
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.
6

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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
President’s 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 FDA’s PEPFAR web page, available at https://www.fda.gov/international-programs/presidents-emergencyplan-aids-relief-pepfar.

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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 applicant’s
recommendation of the appropriate FDA
review discipline
Additional Background

Yes

No or N/A

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
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.

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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 Agency’s response.

Previous CC
Number

Submission
Date

Concise Statement of
Inquiry

Concise Statement of Agency’s
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

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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 Agency’s
response(s).

ANDA Number

Meeting Type

Meeting Date

List of attachments provided:
1.
2.
3.

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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 Representative’s 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 Agency’s 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 FDA’s MAPP 5240.3 (Rev. 6), available at
https://www.fda.gov/media/89061/download.

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Select all applicable information included in the submission
 Administrative General
Correspondence14



Bioequivalence 



Drug Product

Biopharmaceutics



Clinical

 Scientific General
Correspondence15
 Drug Substance
(Drug Master File) DMF
#: __________________



Patent or
Exclusivity





Request for
Reconsideration



Facility-Based Major CRL Amendment
Request for Reclassification

Pharm/Tox

14

 Labeling
 Microbiology
 Carve-out16
 Patent
(Section viii
statement)
 Exclusivity
 Dosage Form
 Manufacturing:
 Facility
 Active Pharmaceutical
Ingredient (API)
 Finished Dosage Form (FDF)
(including packaging and
labeling)
 Testing
 Other (e.g., storage, device
constituent)
 Ready for Inspection17
 Process

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.

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Additional background

Yes

No or N/A

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
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).

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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 study’s 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 Agency’s 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
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

Yes

No or N/A

Contains Nonbinding Recommendations
If yes, include docket number and a copy of FDA’s 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
or action that elicited the
amendment (e.g., CRL,
discipline review letter (DRL),
information request (IR), or
tentative approval (TA)

Is this a response to a
CRL?
Yes

No or N/A

Yes

No21

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
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

See section III.C.3 in FDA’s 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).
20

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(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 Agency’s
web page https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeuticequivalence-evaluations-orange-book.

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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 FDA’s 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
Correspondence25



Scientific General
Correspondence26



Bioequivalence

23



Biopharmaceutics

 Clinical

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 FDA’s 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.

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

Drug Substance
DMF #:
__________________





Patent or
Exclusivity



Request for
Reconsideration



Facility-Based Major CRL Amendment
Request for Reclassification



Notice of Commercial Marketing



Drug Product

Pharm/Tox

27



Labeling
 Microbiology
27
 Carve-out
 Patent
(Section
viii
statement)
 Exclusivity
 Dosage Form
 Manufacturing:
 Facility
 Active Pharmaceutical
Ingredient (API)
 Finished Dosage Form
(FDF) (including
packaging/labeling)
 Testing
 Other (e.g., storage
warehouse, device
constituent parts)
 Ready for Inspection28
 Process

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.

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Additional Background

Yes

No or
N/A

Yes

No or
N/A

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
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)
include any of the following?
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).

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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 ProductSpecific 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

FDA’s 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.
30

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For Amendments Only
Type of amendment

Supplement #

Date of FDA
correspondence or
action that elicited the
amendment (e.g.,
Complete Response
Letter (CRL), discipline
review letter (DRL),
information request
(IR), or tentative
approval (TA)):

Is this a response to a
CRL?
Yes

No or
N/A

Unsolicited
Solicited
President’s Emergency
Plan for AIDS Relief
Program (PEPFAR) PostTA31
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 FDA’s PEPFAR web page, available at https://www.fda.gov/international-programs/presidents-emergencyplan-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