0727 Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA - OCT 2022

Generic Drug User Fee Program

0727 Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA - OCT 2022

OMB: 0910-0727

Document [pdf]

Download: pdf | pdf

Formal Meetings
Between FDA and
ANDA Applicants of
Complex Products
Under GDUFA
Guidance for Industry

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
October 2022
Generic Drugs
Revision 1

Formal Meetings
Between FDA and
ANDA Applicants of
Complex Products
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: [email protected]

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)
October 2022
Generic Drugs
Revision 1

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

III.

MEETING TYPES ........................................................................................................... 4
A. Product Development Meetings ............................................................................................ 4
B. Pre-Submission Meetings ....................................................................................................... 5
C. Mid-Cycle Review Meetings and Enhanced Mid-Cycle Review Meetings ........................ 6
D.

IV.

Post-CRL Scientific Meetings ............................................................................................... 8

GDUFA III PERFORMANCE GOALS ......................................................................... 9
A. Performance Goals for Product Development Meetings .................................................... 9
B. Performance Goals for Pre-Submission Meetings ............................................................... 9
C. Performance Goals for MCRMs and EMCRMs ................................................................. 9
D. Performance Goals for Post-CRL Scientific Meetings ...................................................... 10

MEETING REQUESTS ................................................................................................. 10
A. Product Development and Pre-Submission Meetings ....................................................... 10
B. MCRMs and EMCRMs ....................................................................................................... 11
C. Post-CRL Scientific Meetings .............................................................................................. 12

VI.

EVALUATING MEETING REQUESTS ..................................................................... 12
A. Meeting Request Denied ...................................................................................................... 12
B. Meeting Request Granted .................................................................................................... 13

VII.

RESCHEDULING AND CANCELING MEETINGS ................................................ 13
A. Rescheduled Meetings .......................................................................................................... 13
B. Canceled Meetings ................................................................................................................ 14

VIII. MEETING PACKAGE CONTENT AND SUBMISSION.......................................... 16
A. Timing of Submission ........................................................................................................... 16
B. Where and How Many Copies of Meeting Packages to Send ........................................... 16
C.

Meeting Package Content .................................................................................................... 16

IX.

PRE-MEETING COMMUNICATIONS WITH APPLICANTS ............................... 23

PROCEDURES FOR CONDUCT OF MEETINGS ................................................... 24
A. Introductions and Agenda ................................................................................................... 24
B. End of Meeting Summary .................................................................................................... 24
C. Presentations ......................................................................................................................... 25

Contains Nonbinding Recommendations
XI.

DOCUMENTATION AND MEETING MINUTES .................................................... 25

XII.

RESOLUTION OF DISPUTE ABOUT MEETING MINUTES ................................ 25

XIII. APPENDICES ................................................................................................................. 27
A.

SUMMARY OF SCOPE AND CRITERIA FOR MEETINGS .............................
FOR COMPLEX PRODUCTS UNDER GDUFA III.......................................... 27

B. PRE-SUBMISSION MEETING PRESENTATION ...............................................
OUTLINE TEMPLATE FOR PROSPECTIVE ANDA APPLICANTS ........... 30

Contains Nonbinding Recommendations

Formal Meetings Between FDA and ANDA Applicants of Complex
Products 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.

INTRODUCTION

This guidance describes an enhanced pathway for discussions between FDA and a prospective
applicant preparing to submit to FDA or an applicant that has submitted to FDA an abbreviated
new drug application (ANDA) for a complex product, as defined in this guidance. Specifically,
this guidance provides information on requesting and conducting product development meetings,
pre-submission meetings, mid-cycle review meetings (MCRMs), 2 enhanced mid-cycle review
meetings (EMCRMs), and post-complete response letter (CRL) scientific meetings with FDA.
This guidance reflects a unified approach to formal meetings between FDA and prospective
ANDA applicants or ANDA applicants for complex products under the pre-ANDA program and
the ANDA assessment program. 3,4,5 This guidance will assist applicants in generating and
submitting to FDA a meeting request and the associated meeting package for complex products,
This guidance has been prepared by the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and
Research (CDER) at the Food and Drug Administration. You may submit comments on this guidance at any time.
Submit comments to Docket No. FDA-2017-D-5739 (available at https://www.regulations.gov/docket?D=FDA2017-D-5739).
2
The name of this meeting has been changed in the GDUFA Reauthorization Performance Goals and Program
Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter) to mid-cycle review meeting from midreview cycle meeting in the GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years
2018-2022 (GDUFA II commitment letter). The GDUFA III commitment letter is available at
https://www.fda.gov/media/153631/download and the GDUFA II commitment letter is available at
https://www.fda.gov/media/101052/download.
3
For purposes of this guidance, a formal meeting includes any meeting that is requested by a prospective ANDA
applicant or ANDA applicant following the request procedures provided in this guidance, as well as any mee,ing
offered by the Agency following the procedures in this guidance, and includes meetings conducted in any format
(e.g., teleconference, videoconference, face-to-face, written responses only).
4
Applicant is defined as “any person who submits an…ANDA…under this part to obtain FDA approval of a new
drug and any person who owns an approved…ANDA.” 21 CFR 314.3(b). This guidance uses the term ANDA
applicant when discussing meetings that occur after an ANDA is received (i.e., MCRM, EMCRM, and post-CRL
scientific meeting), the term prospective ANDA applicant when discussing meetings that occur before an ANDA is
received (i.e., the product development and pre-submission meetings), and the term applicants when referring to
both prospective ANDA applicants and ANDA applicants.
5
GDUFA III commitment letter at 21-29.
1

Contains Nonbinding Recommendations
as defined in this guidance, that are or will be the subject of ANDAs submitted under section
505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C 355(j)), and as
contemplated in the GDUFA Reauthorization Performance Goals and Program Enhancements
Fiscal Years 2023-2027 (GDUFA III commitment letter). 6
This guidance revises the guidance of the same title issued in November 2020. This revision is
being issued to incorporate information on the complex product meeting types and performance
goals included in the GDUFA III commitment letter, including information on requesting these
meetings and FDA’s procedures for handling these meetings.
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 guidance means that something is suggested or recommended, but
not required.
II.

BACKGROUND

The Generic Drug User Fee Amendments of 2012 (GDUFA I) 7 amended the FD&C Act to
authorize FDA to assess and collect user fees to provide the Agency with resources 8 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 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.
As described in the GDUFA III commitment letter, the pre-ANDA program includes product
development meetings and pre-submission meetings and is intended to clarify regulatory
expectations for prospective ANDA applicants early in product development, assist applicants in
developing more complete submissions, promote a more efficient and effective ANDA
assessment process, and reduce the number of assessment cycles required to obtain ANDA
approval. 9 The ANDA assessment meeting program for complex products includes MCRMs,

See footnote 2.
Title III of the Food and Drug Administration Safety and Innovation Act, Public Law 112-144.
8
User fees are available for obligation in accordance with appropriations acts.
9
GDUFA III commitment letter at 21. The pre-ANDA program includes additional enhancements other than
meetings, such as product-specific guidances, that are outside the scope of this guidance.
6
7

Contains Nonbinding Recommendations
EMCRMs, and post-CRL scientific meetings. 10 The ANDA assessment meeting program is
intended to provide or continue to provide targeted, robust advice to ANDA applicants as they
work to meet the standards for ANDA approval. Some elements of these programs are tailored
to enhance the development of complex generic products. 11
As defined in the GDUFA III commitment letter, complex products generally include:
1. Products with complex active ingredients (e.g., peptides, polymeric
compounds, complex mixtures of [active pharmaceutical ingredients],
naturally sourced ingredients); complex formulations (e.g., liposomes,
colloids); complex routes of delivery (e.g., locally acting drugs such as
dermatological products, complex ophthalmological products, and otic dosage
forms that are formulated as suspensions, emulsions or gels) or complex
dosage forms (e.g., transdermal systems, metered dose inhalers, extendedrelease injectables);
2. Complex drug-device combination products (e.g., pre-filled auto-injector
products, metered dose inhalers); and
3. Other products where complexity or uncertainty concerning the approval
pathway or possible alternative approach would benefit from early scientific
engagement. 12
To facilitate development of complex products that may be submitted in an ANDA, FDA and
industry agreed to different types of meetings between applicants and FDA to discuss the
proposed complex product and support submission of a high-quality, approvable ANDA, as well
as to provide or continue to provide targeted, robust advice as applicants work to meet the
standards for ANDA approval. 13,14

GDUFA III commitment letter at 27-29. In addition to these meetings for complex products, other meetings
described in the GDUFA III commitment letter are available for both complex and non-complex products, including
post-CRL clarification teleconferences, product-specific guidance teleconferences, pre-submission product-specific
guidance meetings, and post-submission product-specific guidance meetings. For more information on these
meetings, see the guidance for industry Post-Complete Response Clarification Between FDA and ANDA Applicants
Under GDUFA (October 2022) and the GDUFA III commitment letter at 24-25. For the most recent version of a
guidance, check the FDA Drugs guidance web page at
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
11
GDUFA III commitment letter at 27.
12
GDUFA III commitment letter at 45-46. See also CDER’s Manual of Policies and Procedures (MAPP) 5240.10
Classifying Approved New Drug Products and Drug-device Combination Products as Complex Products for
Generic Drug Development Purposes, available at https://www.fda.gov/media/157675/download.
13
Although only prospective ANDA applicants and ANDA applicants can request meetings under the pre-ANDA
and ANDA Assessment Meeting programs (GDUFA III commitment letter at 21, 27), an applicant may include
other relevant entities in the meeting, e.g., consultants or drug master file holders.
14
FDA has received, responded to, and granted certain meeting requests for products that do not fit within the
definition of a complex product as defined in the GDUFA III commitment letter and as used in this guidance.
Meeting requests for products that do not fit within the scope of this guidance will be granted based on the workload
and availability of staff and the anticipated value to the ANDA assessment process.
10

Contains Nonbinding Recommendations
III.

MEETING TYPES
A. Product Development Meetings

Product development meetings for complex products that may be submitted in an ANDA provide
a forum for a scientific exchange on specific issues (e.g., a proposed study design, alternative
approach, additional study expectations, or questions), in which FDA agreed to provide targeted
advice regarding an ongoing ANDA development program. 15 To engage in a substantive
discussion, FDA expects that the prospective ANDA applicant has enough knowledge of the
complex product to allow FDA to provide appropriate feedback that will advance product
development early in the process (e.g., the prospective ANDA applicant has generated its own
data to be discussed). FDA recommends that the prospective ANDA applicant submit no more
than one request for a product development meeting for the specific complex product per year,
but FDA anticipates that some prospective ANDA applicants of complex products may request
more than one product development meeting. If, following a product development meeting, a
prospective ANDA applicant is seeking further clarification or has new questions related to what
was discussed at the meeting, we recommend that the applicant submit such a request, with any
new information or data, in a controlled correspondence for FDA’s review. 16 If the prospective
ANDA applicant has new information, data, or questions for Agency input that will not be
adequately addressed in a controlled correspondence, the prospective ANDA applicant can
request an additional product development meeting. The Agency will determine whether to
grant the subsequent product development meeting based on the content of the meeting request
and meeting package and available resources.
The GDUFA III commitment letter identifies when a product development meeting will and
when a product development meeting may be granted. 17
A product development meeting will be granted if, in FDA’s judgment:
1. The requested meeting concerns (1) development of a complex generic product for which
FDA has not issued a product-specific guidance, or (2) an alternative equivalence
evaluation (i.e., change in study type, such as in vitro to clinical) for a complex product
for which FDA has issued a product-specific guidance;
2. FDA determines the prospective ANDA applicant’s meeting package is complete,
including any data generated and specific proposals for product development (e.g., details
regarding the proposed product development plan, such as an alternative study design,
and sufficient justification to support the proposal), as applicable;
3. A controlled correspondence response would not adequately address the prospective
ANDA applicant’s questions; and

GDUFA III commitment letter at 25.
See the guidance for industry Controlled Correspondence Related to Generic Drug Development (December
2020).
17
GDUFA III commitment letter at 25-26.
15
16

Contains Nonbinding Recommendations
4. A product development meeting would significantly improve ANDA assessment
efficiency (e.g., ultimately decrease the number of review cycles for the application). 18
FDA may grant a product development meeting, dependent on available resources, if, in FDA’s
judgment:
1. The requested meeting concerns complex development issues other than those identified
above (e.g., FDA has developed a product-specific guidance and the prospective ANDA
applicant is not proposing an alternative equivalence evaluation);
2. FDA determines the prospective ANDA applicant’s meeting package is complete,
including any data generated and specific proposals for product development (e.g., details
regarding the proposed product development plan, such as an alternative study design,
and sufficient justification to support the proposal), as applicable;
3. A controlled correspondence response would not adequately address the prospective
ANDA applicant’s questions; and
4. A product development meeting would significantly improve ANDA assessment
efficiency (e.g., ultimately decrease the number of review cycles for the application). 19
FDA can meet the product development meeting goal by either conducting a meeting or
providing a meaningful written response that will inform drug development and/or regulatory
decision-making to the prospective ANDA applicant, within the applicable goal date. 20
B. Pre-Submission Meetings
Prospective ANDA applicants of complex products may request a pre-submission meeting. The
purpose of a pre-submission meeting is to provide a prospective ANDA applicant the
opportunity to present unique or novel data or information that will be included in the ANDA
submission such as formulation, key studies, justifications, and/or methods used in product
development, as well as the interrelationship of the data and information in the ANDA. 21
The pre-submission meeting does not include substantive assessment of summary data or full
study reports, but FDA will identify items or information that should be clarified before
submission of the ANDA. The pre-submission meeting is not an opportunity to determine
whether the application is acceptable for receipt. 22

GDUFA III commitment letter at 25.
GDUFA III commitment letter at 26.
20
Ibid.
21
Ibid. In general, a prospective ANDA applicant should not submit questions in a pre-submission meeting request.
If a prospective ANDA applicant has questions related to its ANDA development program, those questions should
be submitted in a product development meeting request.
22
For example, the prospective ANDA applicant should not request or expect guidance on whether certain
components needed for receipt consideration may be omitted from the ANDA.
18
19

Contains Nonbinding Recommendations
FDA anticipates that the pre-submission meeting request will be submitted approximately 6 to 8
months before submission of the ANDA. FDA attendees at the pre-submission meeting will
generally include staff that attended the product development meeting, if held, and ANDA
assessment team members that may assess the ANDA once received.
FDA recommends that a prospective ANDA applicant of a complex product seek FDA’s input
via a product development meeting prior to submitting a request for a pre-submission meeting so
that FDA has knowledge of the prospective ANDA applicant’s development program at the time
of the pre-submission meeting. 23 Prospective ANDA applicants, however, can request a presubmission meeting whether or not they had a product development meeting. FDA agreed to
grant a pre-submission meeting if the prospective ANDA applicant was granted a product
development meeting for the same complex generic product or FDA believes in its sole
discretion that the pre-submission meeting would improve assessment efficiency. 24,25
C. Mid-Cycle Review Meetings and Enhanced Mid-Cycle Review Meetings
During the first assessment cycle, an ANDA applicant for a complex product that was granted a
prior product development meeting for the same complex product may request either an MCRM
or an EMCRM. 26,27,28 The request should be submitted within 7 days 29 of receiving the last midcycle discipline review letter (DRL) (i.e., the latter of the quality DRL and the bioequivalence or
clinical bioequivalence DRL). 30 For example, if the bioequivalence or clinical bioequivalence
DRL is received on November 1, 2022, and the quality DRL is received on November 14, 2022,

A prospective ANDA applicant that had a product development meeting or received written responses only from
FDA is not obligated to request a pre-submission meeting.
24
See GDUFA III commitment letter at 26. FDA can meet the product development meeting goal by either
conducting a meeting or providing a written response. See also section IV.A of this guidance.
25
See GDUFA commitment letter at 26. FDA may also grant pre-submission meetings for a prospective ANDA
applicant of a non-complex product if FDA decides the pre-submission meeting would improve ANDA assessment
efficiency and dependent on available resources. In general, pre-submission meeting requests for non-complex
products will be denied.
26
See GDUFA commitment letter at 27. Such ANDA applicants will be notified in the ANDA Filing
Acknowledgment letter that they are eligible to request an MCRM or EMCRM.
27
ANDA applicants of complex products that have participated only in a pre-submission meeting may be eligible to
request an MCRM or EMCRM during the first assessment cycle at Agency discretion and will be notified in the
ANDA Filing Acknowledgement letter if they are eligible to request an MCRM or EMCRM.
28
ANDA applicants for a drug product designated as a competitive generic therapy (CGT) may be eligible to
request an MCRM during the first assessment cycle. ANDA applicants for a complex drug product designated as a
CGT may be eligible to request an EMCRM during the first assessment cycle. FDA will notify an ANDA applicant
for a drug designated as a CGT of its eligibility to request an MCRM or EMCRM in the ANDA Filing
Acknowledgement letter or the CGT Designation Grant letter. For more information on MCRMs and EMCRMs for
applications for drug products designated as CGT, see the guidance for industry Competitive Generic Therapies
(October 2022).
29
See the GDUFA III Commitment Letter at 47, stating that “[d]ays – unless otherwise specified, means calendar
days.”
30
GDUFA III commitment letter at 27. Mid-cycle DRLs include two separate letters addressing quality potential
deficiencies and bioequivalence potential deficiencies. Applicants eligible for MCRMs or EMCRMs should submit
a meeting request within 7 days of receiving the latter of the two DRLs. If an applicant requests an MCRM or an
EMCRM more than 7 days after receiving the latter of the DRLs or prior to receiving the last DRL, the request will
be denied.
23

Contains Nonbinding Recommendations
the applicant should submit the request for an MCRM or an EMCRM within 7 days of
November 14, 2022.
The MCRM provides the ANDA applicant an opportunity to ask for the rationale for any
deficiency identified in the mid-cycle DRL(s), and/or to ask questions related to FDA’s
assessment of the data or information in the ANDA. 31 An ANDA applicant cannot present any
new data or information at this meeting. 32
The EMCRM provides the ANDA applicant an opportunity to ask questions related to a
proposed scientific path to address possible deficiencies identified in the mid-cycle DRL(s). 33
An applicant may ask questions about potential new data or information to address any possible
deficiencies identified in the mid-cycle DRL(s). 34 FDA will discuss the data and information but
will not provide substantive assessment of the data or information provided by the ANDA
applicant at the meeting. 35
An ANDA applicant should not respond to a DRL prior to the MCRM or EMCRM if the ANDA
applicant intends to ask questions regarding that DRL in an MCRM or EMCRM. If the response
due date for a DRL is before the date by which an ANDA applicant must request the MCRM or
EMCRM, an ANDA applicant should request an extension to respond to that DRL. If an ANDA
applicant responds to a DRL prior to the MCRM or EMCRM, FDA will deny an MCRM or
EMCRM request for the questions related to that DRL or will cancel the MCRM or EMCRM.
FDA will only grant one request in the first assessment cycle (i.e., an MCRM or an EMCRM,
not both) subject to the criteria described above. FDA recommends that an ANDA applicant
request an EMCRM when the ANDA applicant has questions that are within the scope of both an
MCRM and an EMCRM. Requests for MCRMs that contain questions that are within the scope
of both an MCRM and an EMCRM may be granted an MCRM for the questions that are within
the scope of an MCRM and will receive a denial for the questions within the scope of an
EMCRM.
If an ANDA applicant requests and FDA grants an MCRM, FDA will extend the response due
date for the relevant DRL(s), with the response due 15 days after the date of the MCRM.
If an ANDA applicant requests and FDA grants an EMCRM, FDA will extend the ANDA goal
date by 60 days (i.e., FDA will add 60 days to the goal date). 36 FDA also will extend the
response due date for the relevant DRL(s). FDA will recalculate the response due date starting
from the date of the meeting and will extend the response due date by the number of days that
were included for a response in the DRL. 37 For example, if the response was due 30 days after
the DRL was issued, the response will be due 30 days after the date of the EMCRM.
GDUFA III commitment letter at 27-28.
Ibid at 28.
33
Ibid.
34
Ibid.
35
Ibid.
36
Ibid.
37
Ibid.
31
32

Contains Nonbinding Recommendations

An applicant may submit an Unsolicited Amendment after an EMCRM, which could result in an
additional goal date extension, as described in section I(C) of the GDUFA III commitment
letter. 38
In addition, an applicant’s response to a DRL (regardless of whether the applicant had an MCRM
or EMCRM) may result in an additional goal date extension. 39
D. Post-CRL Scientific Meetings
ANDA applicants can request post-CRL scientific meetings for FDA to provide scientific advice
on possible approaches to address deficiencies identified in a CRL related to establishing
equivalence. 40 ANDA applicants can request a post-CRL scientific meeting even if they have
not had a product development meeting. FDA agreed to grant the meeting if it is for a complex
generic product or in FDA’s judgment the request raises issues that are best addressed via this
meeting process and cannot be adequately addressed through controlled correspondence. 41 An
ANDA applicant may have a post-CRL teleconference to seek clarification concerning
deficiencies identified in a CRL (post-CRL clarification teleconference) prior to requesting this
meeting. 42
An ANDA applicant’s post-CRL scientific meeting request must discuss one or more of the
following as it relates to establishing equivalence:
1. New equivalence study needed to address the deficiencies in the design identified in the
CRL;
2. Approach that is different from that submitted in the ANDA, e.g., a change in study type
from in vivo to in vitro;
3. New comparative use human factors study; or
4. New approach to demonstrating sameness of a complex active ingredient. 43
In a post-CRL scientific meeting request, an ANDA applicant can submit questions both within
the scope described above as well as clarifying questions. In contrast, a post-CRL clarification
teleconference is limited to clarifying questions. ANDA applicants that have only clarifying
questions, therefore, should consider requesting a post-CRL clarification teleconference within
10 days of the issuance of the CRL. 44

Ibid at 10. In general, an unsolicited amendment submitted prior to the meeting will not be discussed during the
EMCRM (or MCRM) because the unsolicited amendment is not included in the meeting package.
39
See the guidance for industry Information Requests and Discipline Review Letters Under GDUFA (October
2022). See also the GDUFA III commitment letter at 13.
40
GDUFA III commitment letter at 28.
41
Ibid. at 29.
42
Ibid. at 29, 16. See also the guidance for industry Post-Complete Response Letter Clarification Teleconferences
Between FDA and ANDA Applicants Under GDUFA (October 2022).
43
GDUFA III commitment letter at 28-29.
44
See the guidance for industry Post-Complete Response Letter Clarification Teleconferences Between FDA and
ANDA Applicants Under GDUFA (October 2022).
38

Contains Nonbinding Recommendations

IV.

GDUFA III PERFORMANCE GOALS

As reflected in the GDUFA III commitment letter, FDA committed to meet certain performance
goals associated with the pre-ANDA and ANDA assessment meetings for complex products
described in this guidance. 45 The goals described below in subsections A, B, and D only apply
to meetings related to complex products under GDUFA III (i.e., requests submitted on or after
October 1, 2022, and subject to the criteria described in this guidance). The goals described
below in subsection C only apply to ANDAs found acceptable for filing on or after October 1,
2022, and subject to the criteria described in this guidance. 46
A. Performance Goals for Product Development Meetings
FDA agreed to grant or deny 90 percent of product development meeting requests within 14 days
after receipt of the meeting request. If granted, FDA agreed to conduct 90 percent of product
development meetings within 120 days after the meeting is granted. 47
FDA can also meet the product development meeting goal by providing a meaningful written
response to the prospective ANDA applicant, within the applicable goal date, that will inform
drug development and/or regulatory decision-making. 48
B. Performance Goals for Pre-Submission Meetings
FDA agreed to grant or deny 90 percent of pre-submission meeting requests within 30 days. If
granted, FDA agreed to conduct 90 percent of pre-submission meetings within 60 days of the
meeting request. 49
C. Performance Goals for MCRMs and EMCRMs
If an MCRM is requested and granted, the meeting will take place within 30 days after the date
the ANDA applicant submits the meeting request. If an EMCRM is requested and granted, the
meeting will take place within 90 days after issuance of the last mid-cycle DRL (i.e., the latter of
the quality DRL and the bioequivalence or clinical bioequivalence DRL). 50

Consistent with FDA’s other user fee programs, FDA will calculate the goal date from the day after a submission.
GDUFA III commitment letter at 4. Please also refer to FDA’s guidance for industry Providing Regulatory
Submissions in Electronic Format – Receipt Dates (February 2014) for information on how FDA calculates receipt
dates for regulatory submissions in electronic format. As described in that guidance, requests will be received by
the Agency Monday through Friday from 12:00 a.m. to 11:59 p.m. Eastern Standard Time/Eastern Daylight Time,
excluding Federal holidays and days when the FDA office that will review the request is closed.
46
For ANDAs found acceptable for filing during GDUFA II and that are eligible for a mid-review cycle meeting
under the GDUFA II commitment letter, FDA will initiate scheduling the meeting. See the GDUFA II Commitment
Letter.
47
GDUFA III commitment letter at 26.
48
Ibid.
49
Ibid at 27.
50
Ibid at 28.
45

Contains Nonbinding Recommendations
D. Performance Goals for Post-CRL Scientific Meetings
FDA agreed to grant or deny the post-CRL scientific meeting request within 14 days after receipt
of the request. 51 If granted, FDA agreed to hold the post-CRL scientific meeting within 90 days
after the date the meeting is granted. 52
V.

MEETING REQUESTS

A request for a product development meeting, pre-submission meeting, MCRM, EMCRM, or
post-CRL scientific meeting should be submitted electronically, as explained below in this
section.
If FDA determines that the request does not contain the information specified in this section, the
request will not be considered to be submitted for purposes of GDUFA III performance goals.
A. Product Development and Pre-Submission Meetings
A request for a product development or pre-submission meeting for complex products that may
be submitted in an ANDA should be sent electronically through the CDER Direct NextGen
Collaboration Portal. 53 A request for a pre-submission meeting should clearly indicate whether
the prospective ANDA applicant had a product development meeting with FDA. If no product
development meeting was held, the prospective ANDA applicant should explain why a presubmission meeting should be granted. A product development or pre-submission meeting
request should include the following information:
1. Pre-assigned ANDA number. 54
2. Meeting type being requested (i.e., product development or pre-submission).
3. Reference listed drug (RLD) and its application number.
4. Established Name.
5. Dosage form, route of administration, and strength.
6. A statement indicating whether the submission is being made by the prospective ANDA
applicant or by a U.S. agent on behalf of the prospective ANDA applicant.
Ibid at 29.
Ibid.
53
The CDER Direct NextGen Collaboration Portal may be accessed at
https://edm.fda.gov/EDMIDPLogin/welcome?response_type=code&client_id=0oa1as7rb2poiYTch297&scope=ope
nid%20profile&state=1802935594_1580919665259&redirect_uri=https%3A%2F%2Fedm.fda.gov%2Foidcclient%
2Fedmrp.
54
See information regarding requesting a pre-assigned application number available on FDA’s website at
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/uc
m114027.htm.
51
52

Contains Nonbinding Recommendations

7. Contact person for the meeting (i.e., the person submitting the meeting request), with
their title and affiliation, secure email address, 55 and phone number. This is the person
with whom FDA will communicate about the meeting.
8. The meeting package (see section VIII of this guidance), which should be submitted at
the time of the meeting request for both product development and pre-submission
meetings.
B. MCRMs and EMCRMs
A request for an MCRM or EMCRM should be submitted to the ANDA via the Electronic
Submissions Gateway (ESG) within 7 calendar days of receiving the latter of the quality DRL
and the bioequivalence or clinical bioequivalence DRL. 56 The cover page should identify the
submission as a “Mid-Cycle Review Meeting Request” or “Enhanced Mid-Cycle Review
Meeting Request.” ANDA applicants should also e-mail a copy of the cover page that was
submitted via the ESG to the Regulatory Project Manager.
An MCRM request should include the following information:
1. The specific deficiency(ies) that the ANDA applicant is requesting the rationale for
and/or the questions related to FDA’s assessment of the data or information in the
ANDA.
2. The meeting package (see section VIII of this guidance), which should be submitted at
the time of the request for the MCRM.
An EMCRM request should include the following information:
1. If applicable, the specific deficiency(ies) that the ANDA applicant is requesting the
rationale for and/or the questions related to FDA’s assessment of the data or information
in the ANDA.
2. Questions related to a proposed scientific path to address possible deficiencies identified
in the mid-cycle DRL(s) and any questions about potential new data or information to
address possible deficiencies identified in the mid-cycle DRL(s).
3. The meeting package (see section VIII of this guidance), which should be submitted at
the time of the request for the EMCRM.

Secure email between CDER and ANDA applicants and prospective ANDA applicants is useful for informal
communications when confidential information (e.g., trade secrets or patient information) may be included in the
message. Secure email should not be used for formal regulatory submissions. For more information on establishing
a secure email link with CDER, please contact [email protected].
56
See footnote 30.
55

Contains Nonbinding Recommendations
C. Post-CRL Scientific Meetings
A request for a post-CRL scientific meeting should be submitted to the ANDA via the ESG. The
cover page should identify the submission as a “Post-Complete Response Letter Scientific
Meeting Request.” A complete post-CRL scientific meeting request package should include the
following information:
1. The specific approaches to address deficiencies identified in the CRL related to
establishing equivalence, grouped by discipline. An applicant’s post-CRL scientific
meeting request must discuss one or more of the following as it relates to establishing
equivalence, and the meeting request should identify which one(s) the applicant wants to
discuss: (1) a new equivalence study needed to address the deficiencies in the design
identified in the CRL, (2) an approach that is different from that submitted in the ANDA,
e.g., a change in study type from in vivo to in vitro, (3) a new comparative use human
factors study, or (4) a new approach to demonstrating sameness of a complex active
ingredient. 57
2. The meeting package (see section VIII of this guidance), which should be submitted at
the time of the request for the post-CRL scientific meeting.
VI.

EVALUATING MEETING REQUESTS

FDA will determine whether to grant a product development meeting request, pre-submission
meeting request, MCRM or EMCRM request, or post-CRL scientific meeting request for
complex products, and a response will be provided to the applicant by granting or denying the
meeting request pursuant to the performance goals stated in the GDUFA III commitment letter
(see section IV of this guidance) and as described below. Although applicants can request a
particular format, FDA evaluates each meeting request and determines whether or not the request
should be granted, the final meeting type, and the appropriate format.
A.

Meeting Request Denied

If a meeting request is denied, written notification to the applicant will include an explanation of
the reason for the denial.
Denials of meeting requests submitted in conformity with the GDUFA III performance goals will
be based on a substantive reason, not merely on the absence of a minor element of the meeting
request or meeting package items. For example:
•

A product development or pre-submission meeting request may be denied because the
product does not meet the criteria for a complex product as provided in section II of this
guidance or because a meeting is premature for the stage of product development in light
of the insufficiency of the data generated.

GDUFA III commitment letter at 28-29.
12

Contains Nonbinding Recommendations
•

An MCRM request or EMCRM request may be denied if the applicant did not participate
in a prior product development meeting or pre-submission meeting or the product does
not meet the criteria for a complex product as provided in section II of this guidance. In
addition, the request will be denied if the request is made before issuance of the last midcycle DRL or the request is made more than 7 days after the issuance of the last midcycle DRL.

•

A post-CRL scientific meeting request may be denied because the product does not meet
the criteria for a complex product as provided in section II of this guidance, in FDA’s
judgment the request raises issues that can be adequately addressed through controlled
correspondence, or the meeting request does not discuss one of the following as it relates
to establishing equivalence:
o a new equivalence study needed to address the deficiencies in the design identified in
the CRL,
o an approach that is different from that submitted in the ANDA, e.g., a change in study
type from in vivo to in vitro,
o a new comparative use human factors study, or
o a new approach to demonstrating sameness of a complex active ingredient. 58

If a meeting request is denied, a subsequent request to schedule a meeting will be considered as a
new request (i.e., a request that is assigned a new set of time frames as described in section IV of
this guidance).
B.

Meeting Request Granted

If a request for a meeting is granted, FDA will provide written notification to the applicant of the
decision. FDA may indicate that the request is granted in part for the questions that are
appropriate for the meeting type requested and denied in part for the questions that are not
appropriate for the meeting type requested. If FDA will be providing a written response only
instead of holding a meeting or teleconference, FDA will advise the applicant that a written
response only is forthcoming. If FDA plans to hold a meeting or teleconference, FDA will
schedule the meeting or teleconference by determining the date, time, length, format, and
expected FDA participants. All of the scheduling information will be forwarded to the applicant
either with the notification granting the meeting or teleconference or as soon as possible
following notification that the request has been granted, and the meeting or teleconference will
be scheduled within the specified GDUFA III performance goals (see section IV of this
guidance).
VII.

RESCHEDULING AND CANCELING MEETINGS
A. Rescheduled Meetings

Occasionally, circumstances may arise that necessitate the rescheduling of a meeting. If a
meeting needs to be rescheduled, FDA will work to reschedule it as soon as possible after the
58

GDUFA III commitment letter at 28-29.
13

Contains Nonbinding Recommendations
original date. A new meeting request should not be submitted. Applicants and FDA should take
reasonable steps to avoid rescheduling meetings. For example, if an attendee becomes
unavailable, a substitute can be identified, or comments on the topic that the attendee would have
addressed can be forwarded to the applicant following the meeting. It will be at FDA’s
discretion whether the meeting should be rescheduled depending on the specific circumstances.
A meeting may be rescheduled by FDA if, for example:
1. The assessment team determines that additional information is needed from the applicant
to address the applicant’s questions.
2. Essential attendees are no longer available for the scheduled date and time because of an
emergency.
3. Attendance by additional FDA offices not originally anticipated or requested by the
applicant is critical and the offices’ availability precludes holding the meeting on the
original date.
4. There is a regulatory policy issue that is yet to be resolved that may affect the response to
the applicant’s questions.
5. The Federal Government is closed or opening is delayed due to inclement weather,
emergency, or other reason.
If an applicant requests that a meeting be rescheduled, FDA will evaluate the request and it will
be at FDA’s discretion whether to grant the request to reschedule. FDA will try to ensure a
rescheduled meeting occurs within the goal date (see section IV of this guidance). 59 If FDA, in
its discretion, decides to reschedule the meeting and is unable to reschedule it within the original
goal date, FDA will notify the applicant of the reason for the rescheduled date, and FDA will still
consider the performance goal met if the Agency is able to schedule and conduct the meeting
within 30 days of the original goal date.
B. Canceled Meetings
Occasionally, circumstances may arise that necessitate the canceling of a meeting. If a meeting
is canceled, a subsequent request to schedule a meeting will be considered a new request.
Applicants and FDA should take reasonable steps to avoid canceling meetings (unless the
meeting is no longer necessary). It will be at FDA’s discretion whether the meeting should be
canceled depending on the specific circumstances.
A product development meeting may be canceled if, for example:
1. The prospective ANDA applicant withdraws the meeting request,
FDA does not recommend that applicants request to reschedule MCRMs or EMCRMs due to the timeframe for
conducting these meetings (see section IV.C) and because these meetings are conducted during the assessment
cycle.
59

Contains Nonbinding Recommendations

2. The prospective ANDA applicant informs FDA that its questions have been adequately
answered by the preliminary written comments, or
3. FDA issues product-specific guidance on establishing bioequivalence to the RLD that is
the basis of submission for the prospective ANDA applicant and which addresses the
questions in the meeting package. 60
If a prospective ANDA applicant requests to cancel a product development meeting after
preliminary responses are issued, FDA will count the performance goal as met. If FDA cancels
the meeting on its own initiative, the meeting request will not be counted for performance goal
purposes.
A pre-submission meeting may be canceled if, for example:
1. the prospective ANDA applicant withdraws the meeting request, or
2. the applicant submits the ANDA.
An MCRM may be canceled if, for example:
1. The ANDA applicant withdraws the meeting request, or
2. The ANDA applicant submits a response to the DRL(s) that the questions in the meeting
package are based on.
An EMCRM may be canceled if, for example:
1. The ANDA applicant withdraws the meeting request,
2. The ANDA applicant informs FDA that its questions have been adequately answered by
preliminary written comments, or
3. The ANDA applicant submits a response to the DRL(s) that the questions in the meeting
package are based on.
If an ANDA applicant requests to cancel an EMCRM after the goal date has been extended, the
extended goal date will remain.
A post-CRL scientific meeting may be canceled if, for example:
1. The ANDA applicant withdraws the meeting request,
FDA publishes new and revised product-specific guidances describing the Agency’s current recommendations for
demonstrating bioequivalence and certain other approval requirements. Please check for the availability of new and
revised product-specific guidances in the Federal Register and on the FDA website at the following address:
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm075207.htm.

Contains Nonbinding Recommendations

2. The ANDA applicant informs FDA that its questions have been adequately answered by
the preliminary written comments, or
3. The applicant submits a response to the CRL.
VIII. MEETING PACKAGE CONTENT AND SUBMISSION
Pre-meeting preparation is critical for achieving a productive discussion or exchange of
information at meetings for complex products that may be submitted or have been submitted in
an ANDA. Preparing the meeting package should help the applicant focus on describing its
principal areas of interest. The meeting package should provide information relevant to the
discussion topics and enable FDA to prepare adequately for the meeting. The meeting package
should clearly indicate the type of meeting the applicant is requesting and should include
adequate information for FDA to assess the potential utility of the meeting and to identify the
appropriate staff that should attend the meeting.
A. Timing of Submission
The meeting package should be submitted to FDA so that it is received concurrently with the
meeting request.
B. Where and How Many Copies of Meeting Packages to Send
Both the product development and pre-submission meeting packages should be submitted
electronically to the CDER Direct NextGen Collaboration Portal at the same time as the meeting
request.
The MCRM, EMCRM, and post-CRL scientific meeting packages should be submitted to the
ANDA via the ESG at the same time as the meeting request.
It is not necessary to submit any paper copies of the meeting package.
C. Meeting Package Content
The meeting package should provide information relevant to the product, development stage, and
meeting type requested, in addition to any supplementary information needed to help FDA
develop responses to issues raised by the applicant. The meeting package should contain
sufficient detail to meet the intended meeting objectives.
To facilitate FDA review, the meeting package content should be organized according to the
proposed agenda. The meeting package should be a sequentially paginated document (individual
sections can be numbered separately, as long as there is an overall pagination covering the whole
submission) with a table of contents, appropriate indices, appendices, cross-references, and tabs
differentiating sections.

Contains Nonbinding Recommendations

1. General Meeting Package Content
Meeting packages for each of the meeting types included in this guidance generally should
include the following information:
1. Pre-assigned ANDA number or ANDA number.
2. Established name.
3. RLD and application number.
4. A brief statement of the purpose and objectives of the meeting. This statement should
include a brief background of the issues underlying the agenda.
2. Product Development Meetings
For product development meetings, in addition to the information in subsection 1 – General
Meeting Package Content, meeting packages should generally also include:
1. Chemical structure.
2. Dosage form, route of administration, and dosing regimen (frequency and duration).
3. Proposed indications (e.g., prospective ANDA applicant is not seeking approval for
all of the RLD’s indications).
4. A brief statement indicating how the product meets the criteria for a complex product
(see section II).
5. A background section that includes the following:
•

A brief history of the development program.

•

The status of product development.

Contains Nonbinding Recommendations
6. The requested format 61 — face-to-face, 62 videoconference, 63 teleconference, 64 or
written response only. 65 For requested formats other than written response only, the
meeting request package should also include the following information:
•

A proposed agenda and discussion topics, outlining how the 60-minute time frame
allotted for the product development meeting should be apportioned for
discussing each agenda item.

•

Suggested dates and times (e.g., morning or afternoon) for the meeting that are
within the time frame for a product development meeting. Nonavailability dates
and times should also be included.

•

A list of all individuals, with their titles and affiliations, who will participate in
the requested meeting from the applicant’s organization, including consultants
and interpreters. 66

7. A list of questions for discussion, grouped by discipline, as applicable, with each
question clearly numbered (e.g., 1, 2, 3 without subquestions). For each question,
there should be a brief explanation of the context and purpose of the question and any
supporting rationale or data, as applicable. The prospective ANDA applicant should
consider the duration of the proposed meeting when determining the proposed
questions. The package should be organized such that following a summary list of all
questions, each question is followed by the corresponding supporting justification,
rationale, or data, as applicable, followed by the next question.
8. Data to support discussion organized by discipline and question. The level of detail
should be appropriate to the meeting type requested and the product development
stage (e.g., if an approach or alternative approach is proposed for establishing
equivalence, sufficient rationale together with at least preliminary data should be
provided).

For prospective ANDA applicants that meet the criteria in the GDUFA III commitment letter for a product
development meeting, FDA will generally grant the prospective ANDA applicants’ requested format. If FDA, in its
discretion, provides the opportunity for a product development meeting to a prospective ANDA applicant that does
not meet the criteria in the GDUFA III commitment letter, FDA has the discretion to select the format.
62
Face-to-face meetings are those in which the majority of attendees participate in person at the FDA.
63
Videoconferences are meetings in which the attendees participate from various remote locations via a video
connection.
64
Teleconference means a verbal communication by telephone, and not a written response, unless otherwise agreed
to by the applicant. GDUFA III commitment letter at 48.
65
Written response only responses are sent in lieu of a meeting or teleconference when requested by or otherwise
agreed to by the applicant.
66
The applicant should notify their FDA point of contact (POC) immediately if the list of meeting participants from
the applicant’s organization and consultants changes. In this situation, FDA may reschedule the meeting if the
revised list of meeting participants requires additional FDA personnel. In the event this meeting is ultimately
rescheduled outside the 120-day window, FDA will consider the GDUFA III goal of conducting the meeting within
120 days of granting the meeting request met.
61

Contains Nonbinding Recommendations
3. Pre-Submission Meetings
For pre-submission meetings, in addition to the information in subsection 1 – General Meeting
Package Content, meeting packages should generally also include: 67
1. Chemical structure.
2. Dosage form, route of administration, and dosing regimen (frequency and duration).
3. Proposed indications (e.g., prospective ANDA applicant is not seeking approval for
all of the RLD’s indications).
4. A brief statement indicating how the product meets the criteria for a complex product
(see section II).
5. A background section that includes the following:
•

A brief history of the development program.

•

The status of product development.

6. The requested format 68 — face-to-face or videoconference. The meeting request
package should also include the following information:
•

A proposed agenda and discussion topics, outlining how the 60-minute time frame
allotted for the pre-submission meeting should be apportioned for discussing each
agenda item.

•

Suggested dates and times (e.g., morning or afternoon) for the meeting that are
within the time frame for a pre-submission meeting. Nonavailability dates and
times should also be included.

In general, high-level information is sufficient for the pre-submission meeting package. The meeting package can
be in the format of a draft meeting presentation. For a suggested pre-submission meeting presentation outline
template with recommendations on information that should be included, see Appendix B of this guidance. If the
meeting request is granted, the draft presentation may be updated up to 21 days prior to the meeting date so that
FDA may provide preliminary comments on the presentation 5 days before the meeting. The final presentation
should be sent to the FDA no later than 48 hours before the meeting.
68
For prospective ANDA applicants that meet the criteria in the GDUFA III commitment letter for a pre-submission
meeting, FDA will generally grant the prospective ANDA applicants’ requested format. If FDA, in its discretion,
provides the opportunity for a pre-submission meeting to a prospective ANDA applicant that does not meet the
criteria in the GDUFA III commitment letter, FDA has the discretion to select the format. Due to the nature of the
pre-submission meeting, teleconference and written response only are not options for this meeting type.
67

Contains Nonbinding Recommendations
•

A list of all individuals, with their titles and affiliations, who will participate in
the requested meeting from the applicant’s organization, including consultants
and interpreters. 69

7. Whether the prospective applicant had a product development meeting with FDA. If
no product development meeting was held, the prospective applicant should explain
why a pre-submission meeting should be granted.
8. The event IDs for previously granted product development meeting(s).
9. A summary of the advice provided at the product development meeting(s).
10. The estimated timeline for when the prospective ANDA applicant plans to submit its
ANDA. 70
11. Unique or novel data or information that will be included in the ANDA submission,
such as formulation, key studies, justifications, and/or methods used in product
development, as well as the interrelationship of the data and information in the
ANDA.
4. MCRMs
For MCRMs, in addition to the information in subsection 1 – General Meeting Package Content,
meeting packages should generally also include:
1. The specific deficiency(ies) that the applicant is requesting the rationale for and/or the
questions related to FDA’s assessment of the data or information in the ANDA.
2. The requested format 71 — teleconference or written response only. For requested
teleconferences, the request package should also include the following information:
•

A proposed agenda outlining how the 30-minute time frame allotted for the
MCRM should be apportioned for discussing each agenda item.

The applicant should notify their FDA POC immediately if the list of meeting participants from the applicant’s
organization and consultants changes. In this situation, FDA may reschedule the meeting if the revised list of
meeting participants requires additional FDA personnel. In the event this meeting is ultimately rescheduled outside
the 60-day window, FDA will consider the GDUFA III goal of conducting the meeting within 60 days of granting
the meeting request met.
70
FDA recommends that a prospective ANDA applicant submits its pre-submission meeting request approximately
6 to 8 months before submission of the ANDA.
71
For applicants that meet the criteria in the GDUFA III commitment letter for an MCRM, FDA will generally grant
the ANDA applicants’ requested format. If FDA, in its discretion, provides the opportunity for an MCRM to an
ANDA applicant that does not meet the criteria in the GDUFA III commitment letter, FDA has the discretion to
provide a written response only instead of a teleconference.
69

Contains Nonbinding Recommendations
•

Suggested dates and times (e.g., morning or afternoon) for the teleconference that
are within the time frame of an MCRM. Nonavailability dates and times should
also be included.

•

A list of all individuals, with their titles and affiliations, who will participate in
the requested meeting from the applicant’s organization, including consultants
and interpreters. 72

•

A list of specific assessment disciplines asked to participate in the requested
teleconference based on the questions to be discussed. FDA has discretion to
determine which assessment disciplines attend the teleconference. FDA will have
appropriate staff participate in the teleconference to respond to the applicant’s
questions, which may be from different disciplines than the disciplines that the
applicant requested to participate.
5. EMCRMs

For EMCRMs, in addition to the information in subsection 1 – General Meeting Package
Content, meeting packages should generally also include:
1. If applicable, the specific deficiency(ies) that the applicant is requesting the rationale
for and/or the questions related to FDA’s assessment of the data or information in the
ANDA.
2. Questions related to a proposed scientific path to address possible deficiencies
identified in the mid-cycle DRL(s) and any questions about potential new data or
information to address possible deficiencies identified in the mid-cycle DRL(s). 73
3. The requested format 74 — face-to-face, video conference, teleconference, or written
response only. For requested formats other than written response only, the meeting
request package should also include the following information:
•

A proposed agenda outlining how the 60-minute time frame allotted for the
EMCRM should be apportioned for discussing each agenda item.

The applicant should notify their FDA POC immediately if the list of participants from the applicant’s
organization and consultants changes. In this situation, FDA may reschedule the teleconference if the revised list of
teleconference participants requires additional FDA personnel. In the event this teleconference is ultimately
rescheduled outside the 30-day window, FDA will consider the GDUFA III goal of conducting the teleconference
within 30 days of the date the applicant submits the request met.
73
As stated in section III.B of this guidance, FDA will not provide substantive assessment of the data or information
provided by the applicant at the meeting.
74
For applicants that meet the criteria in the GDUFA III commitment letter for an EMCRM, FDA will generally
grant the applicant’s requested meeting format. If FDA, in its discretion, provides the opportunity for an EMCRM
to an ANDA applicant that does not meet the criteria in the GDUFA III commitment letter, FDA has the discretion
to provide a teleconference or written response only instead of a meeting.
72

Contains Nonbinding Recommendations
•

Suggested dates and times (e.g., morning or afternoon) for the meeting that are
within the time frame of an EMCRM. Nonavailability dates and times should
also be included.

•

A list of all individuals, with their titles and affiliations, who will participate in
the requested meeting from the applicant’s organization, including consultants
and interpreters. 75

•

A list of specific assessment disciplines asked to participate in the requested
meeting or teleconference based on the questions to be discussed. FDA has
discretion to determine which assessment disciplines attend the meeting. FDA
will have appropriate staff participate in the meeting or teleconference to respond
to the applicant’s questions, which may be from different disciplines than the
disciplines that the applicant requested to participate.
6. Post-CRL Scientific Meetings

For post-CRL scientific meetings, in addition to the information in subsection 1 – General
Meeting Package Content, meeting packages should generally also include:
1. A brief statement indicating how the product meets the criteria for a complex product
(see section II).
2. The specific approaches to address deficiencies identified in the CRL, grouped by
discipline, with data to support discussion. The meeting package must discuss one or
more of the following: (1) a new equivalence study needed to address the deficiencies
identified in the CRL; (2) an approach that is different from that submitted in the
ANDA, e.g., a change in study type from in vivo to in vitro; (3) a new comparative
use human factors study; or (4) a new approach to demonstrating sameness of a
complex active ingredient.
3. The requested format 76 – face-to-face, videoconference, teleconference, or written
response only. For requested formats other than written response only, the meeting
request package should also include the following information:

The applicant should notify their FDA POC immediately if the list of meeting participants from the applicant’s
organization and consultants changes. In this situation, FDA may reschedule the meeting if the revised list of
meeting participants requires additional FDA personnel. In the event this meeting is ultimately rescheduled outside
the 90-day window, FDA will consider the GDUFA III goal of conducting the meeting within 90 days after issuance
of the last mid-cycle DRL met.
76
For ANDA applicants that meet the criteria in the GDUFA III commitment letter for a post-CRL scientific
meeting, FDA will generally grant the applicant’s requested format. If FDA, in its discretion, provides the
opportunity for a post-CRL scientific meeting to an ANDA applicant that does not meet the criteria in the GDUFA
III commitment letter, FDA has the discretion to provide a teleconference or written response only instead of a
meeting or direct the ANDA applicant to utilize the controlled correspondence pathway.
75

Contains Nonbinding Recommendations

IX.

•

A proposed agenda and discussion topics, outlining how the 60-minute time frame
allotted for the post-CRL scientific meeting should be apportioned for discussing
each agenda item.

•

Suggested dates and times (e.g., morning or afternoon) for the meeting that are
within the time frame for a post-CRL scientific meeting. Nonavailability dates
and times should also be included.

•

A list of all individuals, with their titles and affiliations, who will participate in
the requested meeting from the applicant’s organization, including consultants
and interpreters. 77

•

PRE-MEETING COMMUNICATIONS WITH APPLICANTS

For a product development meeting, if FDA is not providing a written response to the
prospective ANDA applicant, FDA agreed to provide preliminary written comments to the
prospective ANDA applicant’s point of contact and FDA intends to provide such comments 5
calendar days before the meeting. 78 For a pre-submission meeting, FDA agreed to provide
preliminary written comments to the prospective ANDA applicant’s point of contact 5 calendar
days before the meeting. 79
In general, FDA does not intend to provide preliminary written comments in advance of an
MCRM. For EMCRMs, FDA intends to provide preliminary written comments to the ANDA
applicant’s point of contact no later than 3 calendar days before the meeting.
For post-CRL scientific meetings, FDA intends to provide preliminary written comments to the
ANDA applicant’s point of contact no later than 5 calendar days before the meeting.
Communications before the meeting between applicants and FDA, including preliminary written
comments, can serve as a foundation for discussion or as the final meeting responses.
Nevertheless, preliminary written comments should not be construed as final unless there is
The applicant should notify their POC immediately if the list of meeting participants from the applicant’s
organization and consultants changes. In this situation, FDA may reschedule the meeting if the revised list of
meeting participants requires additional FDA personnel. In the event this meeting is ultimately scheduled outside
the 90-day window, FDA will consider the GDUFA III goal of conducting the meeting within 90 days of granting
the meeting request met.
78
GDUFA III commitment letter at 26.
79
Ibid. at 27.
77

Contains Nonbinding Recommendations
agreement between the applicant and FDA that additional discussion is not necessary for any
question (i.e., when the meeting is canceled because the applicant is satisfied with FDA’s
preliminary written comments), or the applicant and FDA agree a particular question is
considered resolved, allowing extra time for discussion of other questions during the meeting.
After receiving the preliminary written comments, the applicant should provide an updated
agenda with its list of questions for discussion in order of priority, no later than 48 hours before
the scheduled meeting. Preliminary written comments communicated by FDA should not
generate the submission of new questions, and new questions will not be entertained at the
meeting.
X.

PROCEDURES FOR CONDUCT OF MEETINGS
A. Introductions and Agenda

Product development and pre-submission meetings for complex products will be chaired by an
FDA staff member and will begin with introductions 80 and a statement of the agenda.
In general, for product development meetings, the meeting participants will discuss the questions
posed and the data provided by the prospective ANDA applicant to assist its complex product
development program.
In general, for pre-submission meetings, the prospective ANDA applicant will present the unique
or novel data or information that will be included in the ANDA submission.
The Regulatory Project Manager assigned to the ANDA will manage the MCRM or the
EMCRM. In general, for MCRMs, the meeting participants will discuss the questions posed
about the rationale for any deficiency identified in the mid-cycle DRL, and/or questions related
to the FDA’s assessment of the data or information in the ANDA. In general, for EMCRMs, the
meeting participants will discuss the questions related to a proposed scientific path to address
possible deficiencies in the mid-cycle DRL(s).
Post-CRL scientific meetings for complex products will be chaired by an FDA staff member and
will begin with introductions 81 and a statement of the agenda. In general, the meeting
participants will discuss scientific advice on possible approaches to address deficiencies
identified in the CRL related to establishing equivalence.
B. End of Meeting Summary
Before the end of the meeting, FDA attendees and the applicant attendees should summarize the
important discussion points, agreements, clarifications, and action items. Generally, the
applicant will be asked to present the summary to ensure that there is mutual understanding of
In general, FDA attendees may include, as applicable, additional staff from CDER’s OGD, Office of
Pharmaceutical Quality (OPQ), Office of Surveillance and Epidemiology, and Office of New Drugs. Center for
Devices and Radiological Health staff may also attend if the complex product has a device component.
81
See footnote 80.
80

Contains Nonbinding Recommendations
meeting outcomes and action items. FDA staff can add or further clarify any important points
not covered in the summary, and these items can be added to the meeting minutes. The summary
can be done at the end of the meeting or after the discussion of each question.
C. Presentations
Presentations by applicants are not generally needed for meetings, except for pre-submission
meetings, because the information necessary for review and discussion should be part of the
meeting package. If an applicant plans to make a presentation, the presentation should be
discussed ahead of time with the FDA point of contact to ensure that FDA has the presentation
materials ahead of the meeting, if possible. All presentations should be kept brief to maximize
the time available for discussion.
The length of the meeting will not be increased to accommodate a presentation. If a presentation
contains more than a small amount of content distinct from clarifications or explanations of
previous data, or contains data that were not included in the original meeting package submitted
to FDA for review, FDA staff may not be able to provide comments on the new information.
FDA does not expect that the ANDA applicant attendees of the MCRMs will provide any
presentations.
XI.

DOCUMENTATION AND MEETING MINUTES

Documentation of meeting outcomes, agreements and disagreements, issues for further
discussion, and action items is critical to ensuring that this information is preserved for meeting
attendees and for future reference. FDA minutes are the official record of the meeting. FDA
agreed to issue the official, finalized minutes to the prospective ANDA applicant within 30 days
after the product development or pre-submission meeting. 82 FDA intends to issue the official,
finalized minutes to the ANDA applicant for the MCRM, EMCRM, or post-CRL scientific
meeting within 30 days after the meeting.
XII.

RESOLUTION OF DISPUTE ABOUT MEETING MINUTES

On occasion, there may be disputes regarding the accuracy and sufficiency of the minutes of a
product development meeting, pre-submission meeting, MCRM, EMCRM, or post-CRL
scientific meeting. An applicant requesting additional clarification of the meeting minutes issued
by FDA should contact the assigned FDA point of contact. FDA recommends that the applicant
submit its concerns about the meeting minutes in writing to FDA within 10 calendar days of
receipt of the official meeting minutes. This process addresses issues with the meeting minutes
only.
If a prospective ANDA applicant needs to discuss additional issues that were not addressed at the
product development or pre-submission meeting, the prospective ANDA applicant should submit
82

GDUFA III commitment letter at 26 and 27.
25

Contains Nonbinding Recommendations
a controlled correspondence or a new meeting request. If an ANDA applicant needs to discuss
additional issues that were not addressed at the MCRM or EMCRM, the ANDA applicant should
contact the Regulatory Project Manager. 83 If an ANDA applicant needs to discuss additional
issues that were not addressed at the post-CRL scientific meeting, the ANDA applicant should
submit a controlled correspondence or a request for another post-CRL scientific meeting.
If, after following up as described above, there are still significant differences in the applicant’s
and FDA’s understanding of the content of the official meeting minutes, the applicant should
notify FDA in writing with respect to specific disagreements. The applicant should submit the
correspondence to its application or, if there is no application, submit a letter to the division
director of the division that chaired the meeting, with a copy to the FDA point of contact
describing the concern.
The applicant’s concerns will be taken under consideration by the assessment division and senior
management, if senior management was present at the meeting. If the minutes are determined to
accurately and sufficiently reflect the meeting discussion, the point of contact will convey this
decision to the applicant, and the minutes will stand as the official documentation of the meeting.
If, after discussions with the applicant, FDA deems it necessary to change the official minutes,
the changes will be documented in an addendum to the official minutes. The addendum will also
document any continued objections. 84

83
84

The applicant should not submit a request for another MCRM or EMCRM. FDA will deny such a request.
Any addendum will be shared with the applicant by FDA.
26

Contains Nonbinding Recommendations
XIII. APPENDICES
A. Summary of Scope and Criteria for Meetings for Complex Products Under
GDUFA III
Meeting Type
Product Development

Purpose/Scope
(a) Development of a
complex product for
which FDA has not issued
product-specific guidance

•
•
•

•

(b) Alternative equivalence
evaluation for a complex
product for which FDA
has issued a productspecific guidance

•
•
•

•

•
•
•

•

Criteria
Additional Considerations
Meets the purpose/scope
Prospective ANDA
applicant submits a
complete meeting package
Controlled correspondence
response would not
adequately address the
prospective applicant’s
questions
Product development
meeting would
significantly improve
ANDA assessment
efficiency
Meets the purpose/scope
Prospective ANDA
applicant submits a
complete meeting package
Controlled correspondence
response would not
adequately address the
prospective applicant’s
questions
Product development
meeting would
significantly improve
ANDA assessment
efficiency
Meets the purpose/scope
• Granting of meeting is
dependent on available
Prospective ANDA
resources
applicant submits a
complete meeting package
Controlled correspondence
response would not
adequately address the
prospective applicant’s
questions
Product development
meeting would
significantly improve
ANDA assessment
efficiency

Contains Nonbinding Recommendations

Meeting Type
Pre-Submission

Mid-Cycle Review

Purpose/Scope
•

•

Criteria

Opportunity for
prospective ANDA
applicants to present
unique or novel data or
information that will be
included in the ANDA
submission such as
formulation, key studies,
justifications, and/or
methods used in product
development, as well as
the interrelationship of the
data and information in
the ANDA

•

Opportunity for the
applicant to ask for
rationale for any
deficiency(ies) identified
in the mid-cycle DRL(s),
and/or to ask questions
related to FDA's
assessment of the data or
information in the ANDA

•

Prospective ANDA
applicant that was granted
a product development
meeting for the same
complex generic product
FDA agreed to grant a presubmission meeting to a
prospective ANDA
applicant of a complex
product that did not have a
product development
meeting if FDA believes
in its sole discretion that
the pre-submission
meeting would improve
assessment efficiency
Held during the first
review cycle with ANDA
applicants of complex
products that were granted
a prior product
development meeting for
the same product
ANDA applicants of
complex products that
have participated only in a
pre-submission meeting
may be eligible to request
an MCRM at Agency
discretion and will be
notified in the ANDA
Filing Acknowledgement
letter if they are eligible to
request an MCRM
Applicants of CGTdesignated ANDAs that
have not had a product
development meeting will
be notified in either the
ANDA Filing
Acknowledgement letter
or CGT Designation Grant
letter if they are eligible to
request an MCRM

Additional
Considerations
•

•

Meeting request should be
submitted approximately 6
to 8 months before
submission of the ANDA
Prospective ANDA
applicant that was granted
a product development
meeting, had a product
development meeting, or
received a written
response only is not
obligated to request a presubmission meeting

MCRMs are requested by
the ANDA applicant. The
applicant will submit a
meeting package and
proposed agenda
An applicant cannot
present any new data or
information at this
meeting

Contains Nonbinding Recommendations
Meeting Type
Enhanced Mid-Cycle
Review

Post-CRL Scientific

Purpose/Scope
•

•

Criteria

Opportunity for the
ANDA applicant to ask
questions related to a
proposed scientific path to
address possible
deficiencies identified in
the mid-cycle DRL(s). An
applicant may ask
questions about potential
new data or information to
address any possible
deficiencies identified in
the mid-cycle DRL(s)

•

Opportunity for ANDA
applicants to seek
scientific advice from
FDA on possible
approaches to address
deficiencies identified in a
CRL related to
establishing equivalence

•

Additional
Considerations

Held during the first
review cycle with ANDA
applicants of complex
products that have were
granted a prior product
development meeting for
the same product
ANDA applicants of
complex products that
have participated only in a
pre-submission meeting
may be eligible to request
an EMCRM at Agency
discretion and will be
notified in the ANDA
Filing Acknowledgement
letter if they are eligible to
request an EMCRM

•

A complex generic
product or in FDA’s
judgment the request
raises issues that are best
addressed via this meeting
process and cannot be
adequately addressed
through controlled
correspondence
An applicant’s post-CRL
scientific meeting request
must discuss one or more
of the four categories
described on pages 28-29
of the GDUFA III
commitment letter and in
section III.D above

•

EMCRMs are requested
by the ANDA applicant.
The applicant will submit
a meeting package and
agenda
FDA will discuss the data
and information but will
not provide substantive
assessment of data or
information provided by
the applicant at the
meeting
If an applicant requests
and FDA grants an
EMCRM, FDA will
extend the goal date and
the response due date for
the relevant DRL(s) as
described on page 28 of
the GDUFA III
commitment letter and in
section III.C above
An applicant can have a
post-CRL teleconference
described on page 16 of
the GDUFA III
commitment letter prior to
requesting this meeting
Applicants are eligible to
request a post-CRL
scientific meeting even if
they have not had a
product development
meeting

Contains Nonbinding Recommendations
B. Pre-Submission Meeting Presentation Outline Template for Prospective ANDA
Applicants
The pre-submission meeting presentation outline template provided below is intended to assist
prospective ANDA applicants in preparing pre-submission meeting presentations, and it includes
suggested items from the Agency for prospective ANDA applicants to present at the presubmission meetings to help orient the discussion. Suggested items for the pre-submission
meeting presentation include, but are not limited to: (1) formulation; (2) new analytical methods;
(3) new statistical methods; (4) novel in vitro drug release testing methods; (5) alternative
bioequivalence study design to the recommendations in the product-specific guidance with
justification for the alternative study design; (6) regulatory history; and (7) summary of generic
development.
Prospective ANDA applicants should address the suggested items, as applicable, and provide
responses/information as appropriate in a concise and clear manner.
Note that the information included below is not an exhaustive list of the information that
prospective ANDA applicants should consider including in their pre-submission meeting
presentation. There may be additional items that should be included in the pre-submission
meeting presentation.
Presentation Outline Template:
1. Pre-Submission Meeting Request Summary
a. Applicant name
b. Anticipated ANDA submission date
c. Reference Listed Drug (RLD)
i. Information on drug substance, dosage form, route of administration
ii. RLD information (RLD number, approval date, application holder)
iii. Indication(s)
iv. Dose and route of administration
d. Reference Standard
i. Indicate if the Reference Standard is the same as the RLD
ii. When the Reference Standard is different from the RLD, include the
Reference Standard information (application number, approval date,
application holder)
e. Complex drug as defined by the GDUFA III commitment letter (indicate all that
apply)
i. Complex active ingredient
ii. Complex formulation
iii. Complex route of delivery
iv. Complex dosage form
v. Complex drug-device combination
vi. Other complexity

Contains Nonbinding Recommendations
2. Justification for the Request (indicate all that apply)
a. Complex drug product
b. ANDA to be submitted within 6 to 8 months of pre-submission meeting request
c. Previous product development meeting
d. Other justification
3. Regulatory History
a. Previous communications with FDA, including but not limited to:
i. Controlled correspondence
ii. Pre-ANDA meeting requests
iii. Suitability petitions
iv. PSG teleconference
v. Pre-submission PSG meeting requests
vi. Competitive generic therapy (CGT) designation requests
4. Summary of Generic Drug Development
a. Provide a brief summary of the status of the generic drug product development
program, including but not limited to:
i. Formulation development
ii. Stability
iii. Status of bioequivalence evaluation
5. Formulation Composition
a. Inactive ingredients exceeding the maximum potency per unit dose and/or
maximum daily exposure specified in the inactive ingredient database
i. No
ii. Yes, with justification
b. Formulation composition assessment
i. Yes, per regulation (e.g., qualitative (Q1) and quantitative (Q2) sameness)
ii. Yes, per PSG recommendations (e.g., Q1/Q2 or “no significant
difference”)
iii. No
c. Formulation composition table
6. Filing
a. Waiver requests, if any
b. Noteworthy items related to filing
7. Labeling
a. Unique or novel labeling differences
b. Labeling differences due to proposed differences in device design
8. Bioequivalence
a. Product-specific guidance (PSG) available
i. No
ii. Yes

Contains Nonbinding Recommendations
b. Deviation from recommendations in PSG
i. No
ii. Yes, with minor deviation (e.g., study design, study population, etc.)
iii. Yes, with major deviation (e.g., an alternative bioequivalence approach,
different statistical analysis, etc.)
c. A brief description of the deviation (if applicable)
d. Failed bioequivalence study with the same or different test formulation
e. In vitro dissolution test conducted for supporting bioequivalence:
i. No
ii. Yes, to request biowaiver for additional strength(s)
iii. Yes, as a pivotal in vitro bioequivalence study
f. Novel bioanalytical methods used in the in vivo bioequivalence study or novel
analytical methods used for in vitro bioequivalence study with justification
g. Novel statistical analysis used for supporting bioequivalence with justification
h. Other novel scientific approaches with justification
9. User Interface Assessment (if applicable)
a. FDA recommends that applicants use and follow the draft guidance for industry
Comparative Analyses and Related Comparative Use Human Factors Studies for
a Drug-Device Combination Product Submitted in an ANDA for the user interface
of the proposed product.
b. If there are design differences identified in the user interface of the proposed
product as compared to the RLD, identify the proposed formulation and/or data
you propose to submit (e.g., in vitro data, comparative human factor study).
c. Applicants are encouraged to include specific considerations for their proposed
product as compared to the RLD with regard to the user interface.
d. Other noteworthy items for user interface assessment.
10. Chemistry Manufacturing Control (CMC)
a. Complex active pharmaceutical ingredient (API)
i. No
ii. Yes
b. Comparative tests for supporting API sameness (if applicable)
c. Novel or unique approaches used in development, manufacture, and control
strategy of the drug product
d. Comparative tests for supporting Q1 sameness/similarity of complex functional
excipients (if applicable)
e. Other noteworthy items for CMC (e.g., complex device and related quality
considerations)
11. Supplemental Materials
a. A list of supplemental materials, if any

File Type	application/pdf
File Title	Guidance for Industry: Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA
Author	FDA/CDER
File Modified	2022-10-05
File Created	2022-10-04