0727 Competitive Generic Therapies Final guidance OCT 2022

Generic Drug User Fee Program

0727 Competitive Generic Therapies Final guidance OCT 2022

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Competitive Generic
Therapies
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

Competitive Generic
Therapies
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/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

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.

COMPETITIVE GENERIC THERAPY DESIGNATION .......................................... 3

IV.

Criteria and Timing for Requests to Designate a Drug as a Competitive Generic
Therapy .............................................................................................................................. 3

Process for Submitting a Request for Designation ........................................................ 6
1.
2.

Requests for Designation Made Prior to Submission of an ANDA........................ 6
Requests for Designation Submitted with an Original ANDA ............................... 7

CONSIDERATIONS FOR EXPEDITED DEVELOPMENT AND REVIEW OF
COMPETITIVE GENERIC THERAPIES .................................................................... 7
A.

Considerations for Expedited Development ................................................................... 8

Actions FDA May Take to Expedite Development ........................................................ 8

1.
Product Development Meetings ............................................................................. 8
2.
Pre-Submission Meetings ...................................................................................... 9
Considerations for Expedited Review ............................................................................. 9

Actions FDA May Take to Expedite Review ................................................................ 10
1.
2.
3.

Mid-Cycle Review Meetings ................................................................................ 10
Coordinated Review of CGTs .............................................................................. 12
Good ANDA Assessment Practices ...................................................................... 12

COMPETITIVE GENERIC THERAPY EXCLUSIVITY......................................... 13
A.

Eligibility for CGT Exclusivity ...................................................................................... 13

CGT Exclusivity Trigger and Scope of CGT Exclusivity ............................................ 15

Relinquishment and Waiver of CGT Exclusivity......................................................... 16

Forfeiture of CGT Exclusivity ....................................................................................... 15

Date of First Commercial Marketing ............................................................................ 16

Relationship Between CGT Exclusivity and 180-Day Patent Challenge Exclusivity 17

Procedural Questions Regarding CGT Exclusivity Determinations .......................... 19

Contains Nonbinding Recommendations

Competitive Generic Therapies
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

The FDA Reauthorization Act of 2017, or FDARA, 2 created a pathway by which FDA may, at
the request of the applicant, designate a drug 3 with “inadequate generic competition” 4 as a
competitive generic therapy (CGT). 5 At the request of the applicant, FDA may also expedite the
development and review of an abbreviated new drug application (ANDA) for a drug designated
as a CGT.
This guidance 6 provides a description of the process that applicants 7 should follow to request
designation of a drug as a CGT and the criteria for designating a drug as a CGT. It also includes
information on the actions FDA may take to expedite the development and review of ANDAs for
drugs designated as CGTs. Finally, it provides information on how FDA implements the
statutory provision for a 180-day exclusivity period for certain first approved applicants that
submit ANDAs for CGTs.
This guidance revises the guidance of the same title issued in March 2020. This revision is being
issued to incorporate information on the meeting types and performance goals included in the
This guidance has been prepared by the Division of Policy Development in the Office of Generic Drug Policy in
the Center for Drug Evaluation and Research at the Food and Drug Administration. You may submit comments on
this guidance at any time. Submit comments to Docket No. FDA-2019-D-0065 (available at
https://www.regulations.gov/docket?D=FDA-2019-D-0065).
1

Public Law 115-52.

For the purposes of this guidance, the term drug is intended to cover any product submitted for approval in an
ANDA, including those products meeting the definition of a combination product under 21 CFR 3.2.

See section 506H(b)(3), (e)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356h(b)(3),
(e)(2)).

The term generic drug refers to a drug that is approved pursuant to section 505(j) of the FD&C Act (21 U.S.C.
355(j)). See section 506H(e)(1).

This guidance has been issued in accordance with section 803(b)(1) of FDARA.

7
For the purposes of this guidance, the term applicant refers to any person developing a drug intended for
submission in an ANDA or any person who submits a drug in an original ANDA.

Contains Nonbinding Recommendations
Generic Drug User Fee Amendments (GDUFA) Reauthorization Performance Goals and
Program Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter). 8
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

On August 18, 2017, FDARA was signed into law. As part of FDARA, the Generic Drug User
Fee Amendments were reauthorized (through Title III) to support timely access to high-quality
affordable generic medicines. FDARA also created other enhancements associated with generic
drugs. Specifically, section 803 of FDARA amended the Federal Food, Drug, and Cosmetic Act
(FD&C Act) to add section 506H, which established a new process to designate, and expedite the
development and review of, certain drugs for which there is inadequate generic competition. 9
FDA recognizes that various factors may influence an applicant’s decision to develop a certain
generic drug. For instance, some drugs may not attract a high level of interest from generic drug
applicants if there is a limited market for those products and/or if the products are more difficult
to develop. Nevertheless, these drugs can play an important role in diagnosing, treating, and
preventing various types of diseases or conditions, and incentivizing generic competition for
these products can help ensure that patients have access to the medicines they need. The
provisions associated with CGTs are intended to incentivize effective development, efficient
review, and timely market entry of drugs for which there is inadequate generic competition.
To facilitate increased competition for these products, FDA may take certain actions to expedite
the development and review 10 of an ANDA for a drug that is designated as a CGT. 11 These
actions, as further described below, may help to clarify the regulatory expectations for a
particular drug, assist applicants in developing a more complete submission, and ultimately

The GDUFA III commitment letter is available at https://www.fda.gov/media/153631/download.

Section 506H(a) of the FD&C Act (“The Secretary may, at the request of an applicant of a drug that is designated
as a competitive generic therapy pursuant to [section 506H(b)], expedite the development and review of an
abbreviated new drug application under section 505(j) for such drug.”).

For the purposes of this guidance, the term review is used to align with the statutory language in section 506H of
the FD&C Act and is intended to describe the Office of Generic Drug’s assessment of submitted data and
information in an ANDA to determine whether the application meets the requirements for approval and its process
for documenting that determination. See section IV.D.3 of this guidance for additional information.

See also section 803(b)(1)(B) of FDARA (requiring FDA to issue guidance to “specify the process and criteria by
which the Secretary makes a designation under section 506H of the [FD&C Act]…[and] specify the actions the
Secretary may take to expedite the development and review of a competitive generic therapy pursuant to such a
designation”).

Contains Nonbinding Recommendations
promote a more efficient and effective ANDA review process in order to help reduce the number
of assessment cycles necessary to obtain ANDA approval.
Historically, the FD&C Act has provided an incentive and potential reward to the first
applicant 12 that, among other things, filed a substantially complete ANDA containing a
paragraph IV certification to a listed patent in FDA’s Approved Drug Products with Therapeutic
Equivalence Evaluations (the Orange Book), 13 which subjected the applicant to the risk of being
sued for patent infringement. Such applicants may qualify for a 180-day period of exclusivity
(hereafter, 180-day patent challenge exclusivity) during which approval of certain subsequent
ANDAs would not be granted. 14
FDARA created a new type of 180-day exclusivity, different from 180-day patent challenge
exclusivity, for the first approved applicant 15 of a drug with a CGT designation for which there
were no unexpired patents or exclusivities listed in the Orange Book at the time of original
submission of the ANDA. This new 180-day exclusivity under FDARA (hereafter, CGT
exclusivity) is intended to incentivize competition for drugs that are not protected by patents or
exclusivities and for which there is inadequate generic competition.
III.

COMPETITIVE GENERIC THERAPY DESIGNATION
A.

Criteria and Timing for Requests to Designate a Drug as a Competitive
Generic Therapy

FDA may designate a drug as a CGT after determining that there is inadequate generic
competition for that drug. The term inadequate generic competition is defined to mean, with
respect to a drug, that there is not more than one approved drug included in the active section of
the Orange Book. 16 This may either be the reference listed drug (RLD) 17 or a drug approved in
an ANDA referencing the same RLD as the drug for which designation as a CGT is sought. 18 If
there is not more than one such drug in the active section of the Orange Book, including if there
The use of the term “first applicant” in this guidance means an applicant that meets the definition set out in
Section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act: “As used in this subsection, the term “first applicant” means an
applicant that, on the first day on which a substantially complete application containing a certification described in
paragraph (2)(A)(vii)(IV) is submitted for approval of a drug, submits a substantially complete application that
contains and lawfully maintains a certification described in paragraph (2)(A)(vii)(IV) for the drug.” The term “first
approved applicant” means an applicant that meets the definition set out in Section 505(j)(5)((B)(v)(III)(bb) of the
FD&C Act.

The Orange Book is available at www.fda.gov/orangebook.

Section 505(j)(5)(B)(iv) of the FD&C Act; see also 21 CFR 314.3(b).

See section 505(j)(5)(B)(v)(III)(bb) of the FD&C Act.

See section 506H(e)(2) of the FD&C Act.

The term reference listed drug is the listed drug identified by FDA as the drug product upon which an applicant
relies in seeking approval of its ANDA. See 21 CFR 314.3.

See section 506H(e)(2)(A)-(B) of the FD&C Act.

Contains Nonbinding Recommendations
are no drugs in the active section of the Orange Book because any approved drugs have been
discontinued from marketing and are reflected as such in the Orange Book, a product is eligible
for designation as a CGT. FDA interprets 506H to describe a process that results in a designation
specific to a particular application and drug product. Accordingly, each applicant that wishes to
request designation of a drug as a competitive generic therapy should submit a request to FDA
for such designation. 19 Once FDA designates a product in an applicant’s ANDA as a CGT, it will
remain designated as a CGT even if there is no longer inadequate generic competition for that
drug prior to approval of the application. 20
Because each strength of a drug is a distinct drug product, in evaluating whether there is not
more than one approved drug included in the active section of the Orange Book, FDA considers
whether the product(s) in the active section is the same strength(s) as the product for which CGT
designation is being sought. For example, if multiple strengths of a drug are approved under the
new drug application (NDA) for the RLD, and some strengths are available for sale and listed in
the active section of the Orange Book, but the particular strength for which CGT designation is
sought is withdrawn from sale and thus is in the discontinued section of the Orange Book, FDA
would not consider the particular strength of the RLD for which CGT designation is sought to be
in the active section of the Orange Book. In this instance, an ANDA submitted referencing this
particular strength of the RLD as its basis of submission may be eligible for designation as a
CGT. 21 For ANDAs submitted or intended for submission pursuant to an approved suitability
petition, 22 FDA determines whether there is more than one product in the active section of the
Orange Book that is either the RLD identified in the petition 23 or an approved ANDA that relied
on the same approved suitability petition as a basis of submission and is pharmaceutically
equivalent to the product for which CGT designation is being sought. If there is not more than
one such drug in the active section of the Orange Book, the product would qualify for CGT
designation.

Each applicant that seeks a CGT designation should submit a request for designation as a CGT. Although a drug
may be a CGT because it has “inadequate generic competition,” FDA does not interpret CGT designation to
automatically apply to all applications for such drug, and CGT designation therefore should be requested for each
application, as described in this section. It should also be noted that CGT designation may not necessarily lead to
eligibility for CGT exclusivity if other requirements described in section 505(j)(5)(B)(v) of the FD&C Act are not
met.
19

For example, inadequate generic competition may have existed at the time a drug is designated as a CGT, but at a
later point in time there could be more than one approved drug in the active section of the Orange Book (e.g.,
because a product that was previously withdrawn from sale is now available for sale or a new application for the
same drug is approved). Both actions could result in there no longer being inadequate generic competition for the
drug designated as a CGT prior to approval of the application for the drug with a CGT designation.

An application containing multiple strengths could have approvals of certain strengths blocked by the CGT
exclusivity of a first approved applicant for these strengths. Because the request must be submitted before or at the
time of submission of the application, a request first made in an amendment or supplement, even an amendment or
supplement providing for a new strength, would not qualify for CGT designation (see Section III.A. of this guidance
for additional information), except in instances where the application has not been received and a refuse-to-receive
letter has been issued.
21

21 CFR 314.93.

See section 506H(e)(2)(A) of the FD&C Act.

Contains Nonbinding Recommendations
Applicants may submit requests to designate a drug as a CGT (hereafter, Requests for
Designation) concurrently with, or at any time prior to, the original ANDA submission. FDA
will not consider Requests for Designation as timely if they are submitted after the submission of
the original ANDA, including as an amendment during filing review. One exception is for an
application for which a refuse-to-receive (RTR) determination has been made, as explained in
the following paragraphs.
FDA may RTR an ANDA that does not satisfy the criteria for a threshold determination that the
application is substantially complete. 24 In such cases, FDA will notify the applicant that FDA
considers the ANDA not to have been received. If the applicant decides to correct the identified
deficiencies in the RTR letter and resubmit the ANDA, the ANDA will be received as of the date
the ANDA is resubmitted (if it is deemed substantially complete).
In this circumstance, a Request for Designation may be considered timely if, after the applicant
receives an RTR letter, the request is included as part of, or is submitted any time prior to, the
resubmission of the amended ANDA that FDA determines to be substantially complete.
However, FDA may deny a Request for Designation if at the time the request is submitted a
Request for Reconsideration and/or Request for Formal Dispute Resolution related to an RTR
decision remains pending with the Agency. If the RTR decision is upheld, ANDA applicants
should submit the Request for Designation as part of the ANDA resubmission (because the
resulting amended ANDA will be considered the original ANDA submission, if FDA finds the
resubmission to be substantially complete). If FDA’s RTR decision is rescinded, such that the
date of receipt for the ANDA will correspond to the date of the initial submission of the ANDA,
FDA will consider any Request for Designation submitted after the date of receipt untimely.
FDA intends to make a determination on a Request for Designation within 60 calendar days of
receipt of the applicant’s request and will send the determination to the applicant via FDA
correspondence. FDA, in assessing whether inadequate generic competition for a particular drug
exists, will rely on the information contained in the Orange Book at the time it makes its
determination. If an applicant believes that the information listed in the Orange Book is
incorrect (e.g., if an applicant has information indicating that a drug listed in the active section of
the Orange Book has been withdrawn from sale), the applicant should submit a controlled
correspondence prior to submitting a Request for Designation seeking correction of the relevant
information in the Orange Book. 25 The Request for Designation should be submitted only after
FDA removes the drug from the active section of the Orange Book.

See generally 21 CFR 314.101(b)(1).

See FDA’s guidance for industry Controlled Correspondence Related to Generic Drug Development (December
2020) for more information on how to submit controlled correspondence to FDA. For the most recent version of a
guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidancedocuments.
25

Contains Nonbinding Recommendations
B.

Process for Submitting a Request for Designation

Requests for Designation Made Prior to Submission of an ANDA

As noted in section III.A of this guidance, Requests for Designation may be made at any time
prior to the submission of an original ANDA or concurrently with the submission of an original
ANDA. If a Request for Designation is made at any time prior to submission of an original
ANDA, the request should be made in writing and may be submitted as a stand-alone request to
FDA or as an accompaniment to the pre-submission facility correspondence (PFC) for an
ANDA. 26 If an applicant plans to request a pre-ANDA meeting for a drug for which it also
wishes to seek designation as a CGT (see section IV.B of this guidance), the applicant should
submit a Request for Designation before submitting a meeting request. The applicant should
obtain, from FDA, a pre-assigned ANDA number prior to submitting a Request for Designation
either as a stand-alone request or as part of a PFC. 27
a.

Content of Requests for Designation

Applicants should include the following information in their cover letter for a Request for
Designation:
•

Pre-assigned ANDA number

•

A statement supporting the Request for Designation under section 506H of the FD&C
Act. This statement should include sufficient identification of the particular drug
product that will serve as the basis of submission for the applicant’s proposed
application (i.e., the application number, the proprietary name (if applicable), and the
strength(s) for the drug for which CGT designation is being sought).

•

Information supporting the applicant’s assertion that there is “inadequate generic
competition” as defined in section 506H(e)(2) of the FD&C Act
b.

Transmitting the Request for Designation through FDA’s Electronic
Submissions Gateway.

Requests for Designation (either as stand-alone requests or as part of a PFC) should be submitted
electronically in electronic common technical document (eCTD) format 28 through the Electronic
Information on the submission of a PFC may be found in FDA’s draft guidance for industry ANDAs: PreSubmission of Facility Information Related to Prioritized Generic Drug Applications (Pre-Submission Facility
Correspondence). When final, this guidance will represent FDA’s current thinking on this topic.
26

Information on how to submit a request for a pre-assigned ANDA number may be found at
https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/requesting-pre-assigned-applicationnumber.
27

See FDA’s guidance for industry Providing Regulatory Submissions in Electronic Format — Certain Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications. See also the eCTD
Technical Conformance Guide at https://www.fda.gov/media/93818/download.

Contains Nonbinding Recommendations
Submissions Gateway (ESG) following the Agency’s instructions. 29 When transmitting via the
ESG, choose “CDER” when selecting the appropriate Center, and choose “eCTD” when
selecting the submission type. A Form FDA 356h should be submitted with the Request for
Designation. Submitting the Form FDA 356h will enable the Agency to process the request.
2.

Requests for Designation Submitted with an Original ANDA

Requests for Designation may also be made concurrently with the submission of an original
ANDA. If applicants submit a Request for Designation concurrently with submission of an
original ANDA, they should prominently identify the request in the cover letter to the
submission in Module 1 of the Common Technical Document. Additionally, the following
information should be included in the cover letter for the request:

IV.

•

Pre-assigned ANDA Number.

•

A statement supporting the Request for Designation under section 506H of the FD&C
Act. This statement should include sufficient identification of the reference listed
drug that is the basis of submission for the applicant’s ANDA (i.e., the NDA number,
the proprietary name, and the strength(s) for the drug for which CGT designation is
being sought).

•

Information supporting the applicant’s assertion that there is “inadequate generic
competition” 30 as defined in section 506H(e)(2) of the FD&C Act.

CONSIDERATIONS FOR EXPEDITED DEVELOPMENT AND REVIEW OF
COMPETITIVE GENERIC THERAPIES

Applicants for drugs that FDA has designated as CGTs may request expedited development and
review of their ANDAs. This section describes factors that FDA will consider in determining
whether to expedite the development and review of an ANDA for a drug designated as a CGT,
and the actions that FDA may take to expedite the development and review of an ANDA for a
drug designated as a CGT. 31 Although FDA will strive to act on applications for drugs

See the Electronic Submissions Gateway web page at https://www.fda.gov/industry/electronic-submissionsgateway for technical details related to submitting documents through FDA’s ESG.
29

As discussed more fully in section V.A, drug products for which there is “inadequate generic competition,” as
defined under section 506H(e)(2), may be designated as a CGT, but may not qualify for 180-day marketing
exclusivity under section 505(j)(5)(B)(v) of the FD&C Act if, at the time of the original ANDA submission,
unexpired patents and/or exclusivities were listed in the Orange Book for the RLD.
30

See section 803(b)(1)(B) of FDARA (requiring FDA to issue guidance to “specify the process and criteria by
which the Secretary makes a designation under section 506H of the [FD&C Act]…[and] specify the actions the
Secretary may take to expedite the development and review of a competitive generic therapy pursuant to such a
designation”).

Contains Nonbinding Recommendations
designated as CGT prior to the GDUFA goal date, a CGT designation does not result in a shorter
GDUFA goal date (see section IV.C of this guidance for more information). 32
A.

Considerations for Expedited Development

To facilitate expedited development, applicants may request to meet with FDA to discuss
specific scientific and/or regulatory questions related to an ongoing development program, or to
discuss the content and format of an ANDA submission, for a drug designated as a CGT. In
determining whether to grant certain requests to facilitate the development of a drug designated
as a CGT, FDA will consider, among other factors:
•

The complexity of developing an application for the specific drug subject to the
request 33

•

The potential public health impact of the product, including the severity of the
condition treated and the size of the impacted patient population, as well as the
availability of therapeutic alternatives

•

The impact on FDA resources and other existing workload commitments

As described more fully below, applicants may request a pre-ANDA meeting (i.e., either a
product development meeting or a pre-submission meeting) for a CGT using the CDER Direct
NextGen Collaboration Portal. 34 FDA will consider requests for meetings that may expedite the
development of a drug designated as a CGT on a case-by-case basis. Such meetings may be
granted for both complex and non-complex products, provided a meeting is determined to be
appropriate considering factors including those set forth above. 35
B.

Actions FDA May Take to Expedite Development

Product Development Meetings

Applicants may submit requests for product development meetings for a drug designated as a
CGT. The purpose of the meeting is to provide a forum for a scientific exchange on specific
issues (e.g., a proposed study design, alternative approach, additional study expectations, or
For the purposes of this guidance, GDUFA refers to the generic drug user fee program codified in the Generic
Drug User Fee Amendments of 2012, the Generic Drug User Fee Amendments of 2017, and the Generic Drug User
Fee Amendments of 2022.
32

For example, if development of an ANDA may raise specific scientific questions, such as when (1) FDA has not
issued a product-specific guidance (PSG) for the drug and published general guidance on bioequivalence is not
applicable or (2) the applicant has proposed an alternative equivalence evaluation (i.e., a change in study type, such
as from an in vitro study to a comparative clinical endpoint study) for a product for which FDA has issued a PSG,
FDA may grant an applicant’s request to meet with FDA to discuss these questions.

See the Pre-ANDA Program web page at https://www.fda.gov/drugs/generic-drugs/pre-anda-program.

Note that while pre-ANDA meetings are intended to expedite the development of drugs designated as a CGT, the
meetings themselves will not necessarily take place on an expedited basis.

Contains Nonbinding Recommendations
questions) and receive FDA’s targeted feedback regarding an ongoing ANDA development
program. To engage in a substantive discussion, FDA expects that the prospective ANDA
applicant has enough knowledge of the product to allow FDA to provide appropriate feedback
that will advance product development early in the process.
Applicants should submit requests for a product development meeting in an appropriate format.
We have outlined a possible appropriate format in FDA’s guidance for industry Formal Meetings
Between FDA and ANDA Applicants of Complex Products Under GDUFA (hereafter, Formal
Meetings guidance). In addition to the applicable information identified in sections V and VIII of
the Formal Meetings guidance, applicants should provide documentation that FDA has
designated the drug under development as a CGT.
2.

Pre-Submission Meetings

An applicant may submit a request for a pre-submission meeting for a drug designated as a CGT
if the applicant wants 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.
A pre-submission meeting does not include substantive review of summary data or full study
reports but provides an opportunity for FDA to identify items or information that should be
clarified before submission of the ANDA.
Applicants should submit requests for pre-submission meetings in an appropriate format. We
have outlined a possible appropriate format in FDA’s Formal Meetings guidance. In addition to
the applicable information identified in sections V and VIII of the Formal Meetings guidance,
applicants should provide documentation that FDA has designated the drug under development
as a CGT.
C.

Considerations for Expedited Review

FDA may take certain actions to expedite the review of an ANDA for a drug that has been
designated as a CGT. FDA generally intends to expedite the review of ANDAs for drugs
designated as CGTs when the applicant has participated in the pre-ANDA meeting program prior
to the submission of the ANDA. FDA generally does not intend to expedite the review of
ANDAs covering CGTs if, at the time of ANDA submission, unexpired patents or exclusivities
were listed in the Orange Book for the RLD. 36 FDA believes that these considerations are
consistent with Congress’s intent to facilitate the efficient development and the timely market
entry of drugs for which there is inadequate generic competition.
As part of expediting the review of a drug that has been designated as a CGT, FDA will strive to
act on the ANDA as soon as possible, including prior to the GDUFA goal date, if possible.
However, an expedited review does not always result in a shorter GDUFA goal date. If an
applicant is seeking a shorter GDUFA goal date, the applicant should determine whether a

See section V.A. of this guidance.

Contains Nonbinding Recommendations
particular drug is eligible for prioritization pursuant to section 505(j)(11) of the FD&C Act 37 or
the criteria in CDER Manual of Policies and Procedures (MAPP) 5240.3 Prioritization of the
Review of Original ANDAs, Amendments, and Supplements. 38 If an ANDA meets the criteria
listed in either section 505(j)(11)(A) of the FD&C Act or MAPP 5240.3, FDA intends to
consider it a priority ANDA, and applicants submitting such priority ANDAs can qualify for a
shorter GDUFA goal date by pre-submitting complete, accurate information regarding facilities
involved in manufacturing processes and testing of the drug that is the subject of the application
not later than 60 days prior to ANDA submission. 39 FDA has provided a draft outline of process
in FDA’s draft guidance for industry ANDAs: Pre-Submission of Facility Information Related to
Prioritized Generic Drug Applications. 40 Priority status will be communicated to applicants in
the ANDA Filing Acknowledgement Letter. 41
D.

Actions FDA May Take to Expedite Review

Mid-Cycle Review Meetings 42

Applicants of an ANDA for a drug product designated as a CGT may be eligible to request a
mid-cycle review meeting (MCRM) during the first assessment cycle. 43 Applicants of an ANDA
for a complex product (including complex drug products designated as a CGT) may be eligible
to request an enhanced mid-cycle review meeting (EMCRM). 44 FDA will notify an applicant of
Section 505(j)(11) of the FD&C Act states, in part, that the Secretary shall prioritize, subject to the process
described in 505(j)(11)(B), and act within 8 months of the date of the submission of an original ANDA that has been
submitted for a drug for which there are not more than 3 approved drugs listed in the Orange Book or for drugs
under drug shortage as defined under section 506E of the FD&C Act (21 U.S.C. 356e).

We update MAPPs periodically. For the most recent version of a MAPP, check the CDER Manual of Policies &
Procedures web page at
https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProc
edures/default.htm.
38

See Section 505(j)(11)(B) of the FD&C Act.

When final, this guidance will represent FDA’s current thinking on this topic.

MAPP 5200.12 Communicating Abbreviated New Drug Application Review Status Updates with Industry

The name of this meeting has been changed in the GDUFA III commitment letter to mid-cycle review meeting
(MCRM) from mid-review cycle meeting (MRCM) 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.
42

FDA offers the ability to request an MCRM to applicants of ANDAs for drug products designated as CGTs to
help expedite review even though such applicants may not meet all the criteria in the GDUFA III commitment letter
for such a meeting. This offer is thus separate from the commitment made to provide an opportunity for these
MCRMs for applicants of complex products that were granted a product development meeting for the same product
under the GDUFA III commitment letter.
43

The GDUFA III commitment letter provides that the EMCRM is available if the application is for a complex
generic product, including a complex drug product designated as a CGT, and the applicant was granted a product
development meeting for the same product. GDUFA III commitment letter at 27. See also the Formal Meetings
guidance. To help expedite the review of ANDAs for complex drug products designated as CGTs, FDA also offers
44

Contains Nonbinding Recommendations
an ANDA for a drug designated as a CGT of its eligibility to request an MCRM or EMCRM
either in the ANDA Filing Acknowledgement Letter or the CGT Designation Grant letter.
The MCRM provides the applicant an opportunity to ask for the rationale for any deficiency
identified in the mid-cycle discipline review letter(s) (DRLs), and/or to ask questions related to
FDA’s assessment of the data or information in the ANDA. 45 An applicant may not present any
new data or information at this meeting. 46 If an MCRM is requested and granted, FDA will
conduct the MCRM for a drug product designated as CGT within 30 days after the date the
applicant submits a meeting request. 47
The EMCRM provides the applicant an opportunity to ask questions related to a proposed
scientific path to address possible deficiencies identified in the mid-cycle DRL(s). 48 An applicant
may ask questions about potential new data or information to address any possible deficiencies
identified in the mid-cycle DRL(s). FDA will discuss the data and information but will not
provide substantive assessment of the data or information during the meeting. If an EMCRM is
requested and granted, FDA agreed to hold the meeting within 90 days after issuance of the last
mid-cycle DRL. 49 FDA will extend the ANDA goal date by 60 days (i.e., FDA will add 60 days
to the goal date) if an applicant requests and FDA grants an EMCRM. 50 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. 51 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.
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. 52
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. 53
the ability to request an EMCRM to certain applicants who were granted a pre-submission meeting for the same
product.
45

GDUFA III commitment letter at 27-28.

Ibid at 28.

FDA will apply the same timeframe for conducting MCRMs for drug products designated as CGT that FDA
committed to for conducting MCRMs for complex drug products. GDUFA III commitment letter at 28. Days,
unless otherwise specified means calendars days. GDUFA III commitment letter at 47.

GDUFA III commitment letter at 28.

Ibid.

Ibid at 10.

GDUFA III commitment letter at 12-13. See also the guidance for industry Information Requests and Discipline
Review Letters Under GDUFA.

Contains Nonbinding Recommendations

Applicants should submit a request for an MCRM or an EMCRM within 7 days of receiving the
last mid-cycle DRL (i.e., the latter of the quality DRL and the bioequivalence or clinical
bioequivalence DRL). 54 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, the
applicant should submit the request for an MCRM or an EMCRM within 7 days of November
14, 2022. Applicants should submit requests for MCRMs or EMCRMs in an appropriate format.
We have outlined a possible appropriate format in the Formal Meetings guidance. In addition to
the applicable information identified in sections V and VIII of that guidance, applicants should
provide documentation that FDA has designated the drug under development as a CGT.
2.

Coordinated Review of CGTs

FDA may involve experienced assessors and regulatory health project management staff in a
collaborative, cross-disciplinary review of an ANDA for a drug designated as a CGT. Senior
management will be involved in the review consistent with the processes described in MAPP
5241.3 Good Abbreviated New Drug Application Assessment Practices. When appropriate, FDA
may also assign a cross-disciplinary project lead for the review team to facilitate an efficient
review of the application, including manufacturing inspections. The cross-disciplinary project
lead will serve as a scientific liaison among members of the assessment team (e.g., those with
expertise in bioequivalence, clinical bioequivalence, quality, or labeling), facilitating coordinated
internal interactions and communications with the applicant through the OGD Regulatory Project
Manager assigned to the ANDA.
3.

Good ANDA Assessment Practices

FDA is committed to improving the predictability and transparency of all ANDA assessments,
including assessments of ANDAs for drugs designated as CGTs, to help minimize the number of
assessment cycles necessary for approval. Program enhancements, as agreed to under the reauthorization of GDUFA, are intended to foster the development of high-quality submissions,
promote the efficiency and effectiveness of the review process, minimize the number of
assessment cycles necessary for approval, increase the overall rate of approval, and facilitate
greater access to generic drugs.
Applicants are encouraged to refer to FDA’s guidance for industry Good ANDA Submission
Practices, which highlights common, recurring ANDA deficiencies that may lead to a delay in
the approval of an ANDA. It also provides draft recommendations to applicants on how to avoid
these ANDA deficiencies with the goal of minimizing the number of assessment cycles
necessary for approval. In conjunction with the Good ANDA Submissions Practices guidance,
FDA issued MAPP 5241.3 Good ANDA Assessment Practices, which establishes good ANDA
assessment practices for the Office of Generic Drugs and the Office of Pharmaceutical Quality to
increase their operational efficiency and effectiveness. FDA will review ANDAs for drugs
designated as CGTs consistent with this MAPP.

GDUFA III commitment letter at 27.

Contains Nonbinding Recommendations

COMPETITIVE GENERIC THERAPY EXCLUSIVITY

FDARA created a new type of 180-day marketing exclusivity period for ANDA applicants of
certain drugs that FDA has designated as CGTs. Specifically, section 808 of FDARA amended
the FD&C Act by adding provisions at section 505(j)(5)(B)(v) and 505(j)(5)(D)(iv) of the FD&C
Act to recognize a 180-day period of exclusivity (hereafter, CGT exclusivity) vis-à-vis certain
other ANDA applicants to the first approved applicant that:
•

Obtains approval of an ANDA for a drug that has been designated as a CGT and for
which there were no unexpired patents or exclusivities listed in the Orange Book for
the relevant RLD at the time the applicant submitted the original ANDA to the
Agency; and

•

Commercially markets such drug within 75 calendar days after the approval of the
ANDA.

As mentioned above, this new type of exclusivity provides an incentive and a reward to generic
drug applicants that submit, obtain approval of, and promptly market ANDAs for drugs with
inadequate generic competition and where the approval of the ANDA would not be blocked by
patents or exclusivities.
A.

Eligibility for CGT Exclusivity

In order to be eligible for CGT exclusivity under section 505(j)(5)(B)(v) of the FD&C Act, an
ANDA applicant must qualify as a “first approved applicant,” which is defined as an applicant
that has submitted an application that:
•

Is for a competitive generic therapy that is approved on the first day on which any
application for such designated competitive generic therapy is approved

•

Is not eligible for a 180-day patent challenge exclusivity period under section
505(j)(5)(B)(iv) for the drug that is the subject of the application for the competitive
generic therapy (discussed further in section V.F. of this guidance)

•

Is not for a drug for which all drug versions have forfeited eligibility for a 180-day
patent challenge exclusivity period under section 505(j)(5)(B)(iv) pursuant to section
505(j)(5)(D) 55 (also discussed further in section V.F of this guidance)

For purposes of the CGT exclusivity provisions, a CGT is defined as a drug that (1) “is
designated as a competitive generic therapy under section 506H [of the FD&C Act]” and (2) “for
which there are no unexpired patents or exclusivities [listed in the Orange Book]…at the time of

See section 505(j)(5)(B)(v)(III)(bb) of the FD&C Act.

Contains Nonbinding Recommendations
submission.” 56 This is distinguishable from how that same term is used in section 506H(b)(3) of
the FD&C Act, in that eligibility for designation as a CGT in section 506H(b)(3) requires only
that FDA determine that a particular drug has inadequate generic competition. In other words,
drugs may be designated as a CGT consistent with section 506H(b)(3) of the FD&C Act but may
not be eligible for 180 days of CGT exclusivity under section 505(j)(5)(B)(v), if unexpired
patents or exclusivities are listed in the Orange Book at the time the applicant submits the
original ANDA for that drug to FDA. 57
Furthermore, a first approved applicant must obtain approval of its ANDA for a CGT “on the
first day on which any application for such competitive generic therapy is approved.” 58 FDA
notes that there can be multiple first approved applicants for the same CGT, if all such ANDA
applicants obtain approval for their ANDAs for the same CGT on the same day, and such
approvals constitute the first ANDA approvals for this CGT.
An ANDA applicant may still qualify as a first approved applicant even if another ANDA
referencing the same RLD, but without a CGT designation, is approved prior to the approval of
the first approved applicant’s ANDA. This is possible because FDA does not consider the prior
ANDA approval to constitute the first approval of an ANDA for a CGT. Approval of an ANDA
for a drug designated as a CGT may, however, block subsequent approvals of ANDAs for the
same drug if that ANDA applicant qualifies as the first approved applicant and the date of
approval is the first day on which any application for such CGT is approved and other criteria are
met. 59
The definition of first approved applicant also includes two additional criteria that an ANDA
applicant must meet to qualify as a first approved applicant. First, the potential first approved
applicant must not otherwise be eligible for 180-day patent challenge exclusivity under section
505(j)(5)(B)(iv) of the FD&C Act for the same drug that has been designated as a CGT. 60
Second, the potential first approved applicant’s ANDA cannot be for a drug for which other
ANDA applicants were eligible for 180-day patent challenge exclusivity under section
505(j)(5)(B)(iv) of the FD&C Act and all such ANDA applicants have forfeited eligibility for
such 180-day patent challenge exclusivity.

See section 505(j)(5)(B)(v)(III)(aa) of the FD&C Act.

This limitation on eligibility for CGT exclusivity applies if there are unexpired patents or exclusivities listed in the
Orange Book at the time of submission of the original ANDA for the CGT, regardless of how the applicant
addresses any unexpired patents or exclusivities. For example, if an applicant submitted a statement under section
505(j)(2)(A)(viii) of the FD&C Act for an unexpired method of use patent listed in the Orange Book at the time of
submission of its ANDA, the applicant would not be eligible for CGT exclusivity.

See section 505(j)(5)(B)(v)(III)(bb) of the FD&C Act.

See section 505(j)(5)(B)(v)(III)(bb)(AA) of the FD&C Act.

See Section 505(j)(5)(B)(v)(III)(bb)(BB) of the FD&C Act.

Contains Nonbinding Recommendations
B.

CGT Exclusivity Trigger and Scope of CGT Exclusivity

The 180-day CGT exclusivity period described under section 505(j)(5)(B)(v) of the FD&C Act is
triggered by the “first commercial marketing of the competitive generic therapy (including the
commercial marketing of the listed drug) 61 by any first approved applicant.” 62 After this
exclusivity is triggered, the 180-day period runs without interruption.
The FD&C Act also specifies that only an ANDA “for a drug that is the same as a competitive
generic therapy for which any first approved applicant has commenced commercial marketing”
can have its approval blocked until the 180-day CGT exclusivity period has been extinguished. 63
As such, once the first approved applicant has commenced commercial marketing, FDA is
restricted from approving ANDAs for a drug that is the same as a CGT approved in the first
approved applicant’s ANDA. 64 Therefore, FDA would not be restricted from approving other
ANDAs covering a drug that is the same as the CGT prior to or after the approval of a first
approved applicant’s ANDA for the CGT unless and until the first approved applicant has
commenced commercial marketing and triggered the exclusivity period. Likewise, the triggering
of the CGT exclusivity period by the first approved applicant would not restrict other ANDA
applicants that were approved prior to the trigger of such exclusivity from commercially
marketing their products.
The first approved applicant’s trigger of the 180-day CGT exclusivity period impacts other first
approved applicants because there is only one CGT exclusivity period available for each drug
designated as a CGT. 65 Any first approved applicant’s trigger of the exclusivity period triggers
the 180-day CGT exclusivity period for all first approved applicants for that CGT, and
exclusivity for all first approved applicants ends 180 days after the initial trigger of that
exclusivity period. Other first approved applicants will benefit from the exclusivity only to the
extent that they commercially market during the exclusivity period.
For the purposes of CGT exclusivity, FDA interprets the statutory phrase “including the commercial marketing of
the listed drug” to mean that exclusivity can be triggered by the marketing of an authorized generic by a first
approved applicant. Such commercial marketing by the first approved applicant within 75 days of approval would
also allow the applicant to avoid the forfeiture provisions under section 505(j)(5)(D)(iv)(see section V.D.,
below). The marketing of an authorized generic prior to approval of an application for a drug with CGT designation
for a first approved applicant will not trigger the 180-day CGT exclusivity period.
61

Section 505(j)(5)(B)(v)(I) of the FD&C Act; see also 21 CFR 314.3(b) (defining commercial marketing).

Section 505(j)(5)(B)(v)(I) of the FD&C Act.

In this case, if the ANDA is otherwise ready for approval, FDA would issue a tentative approval (if an application
that is otherwise ready for approval covers multiple strengths of a drug and only certain strengths are blocked by
CGT exclusivity, FDA would tentatively approve the strengths that are blocked by CGT exclusivity at the same time
that the other strength(s) that are not blocked are approved, provided that the applicant indicates a split approval is
acceptable and submits revised labeling referencing the strengths which are eligible for final approval).

See, e.g., section 505(j)(5)(B)(v)(II) of the FD&C Act. As discussed above, FDA will designate CGTs on a drug
product-by-drug product basis, meaning that different strengths covered under a single ANDA can be considered
different competitive generic therapies. As a result, there are separate 180-day CGT exclusivity periods available for
each strength of the same drug because each strength is a distinct drug product. Thus, it is possible for there to be
different first approved applicants for different strengths of the same drug.
65

Contains Nonbinding Recommendations
Therefore, in order to take full advantage of CGT exclusivity, first approved applicants should be
prepared to begin commercially marketing the drug products approved under their ANDAs as
soon as possible. For planning purposes, applicants can use their assigned GDUFA goal date as
a guide to when action is expected.
C.

Relinquishment and Waiver of CGT Exclusivity

FDA intends to permit a first approved applicant to relinquish and/or grant selective waiver of
CGT exclusivity, similar to FDA’s longstanding practice of permitting relinquishment and
selective waiver of 180-day patent challenge exclusivity. Relinquishment refers to the voluntary
and complete abandonment of eligibility for exclusivity. Selective waiver refers to a first
approved applicant’s waiver of exclusivity to permit approval during the exclusivity period of a
particular ANDA or ANDAs. Relinquishment and selective waiver of CGT exclusivity promote
the overall purpose of the exclusivity — that is, to increase marketplace competition.
A first approved applicant that is eligible for CGT exclusivity may relinquish its exclusivity at
any time, regardless of whether that exclusivity has been triggered. In contrast, a first approved
applicant may only selectively waive CGT exclusivity after the exclusivity period has been
triggered by commercial marketing. 66 As a general matter, when all first approved applicants
have relinquished their claims to CGT exclusivity, FDA may inform other, non-first-approved
applicants that are otherwise eligible for approval that their ANDAs may be approved. For
selective waivers, FDA may notify only the applicable applicant in whose favor the exclusivity
has been waived. 67
D.

Forfeiture of CGT Exclusivity

The FD&C Act includes a provision under which a first approved applicant will forfeit eligibility
for CGT exclusivity. Specifically, section 505(j)(5)(D)(iv) of the FD&C Act provides that the
180-day CGT exclusivity period will be forfeited by “a first approved applicant if the applicant
fails to market the competitive generic therapy within 75 days after the date on which the
approval of the first approved applicant’s application for the competitive generic therapy is made
effective.” 68 Because CGTs are drugs that, by definition, have lacked adequate generic
competition, this forfeiture provision reflects Congress’s intent that a first approved applicant
For example, assume ANDA A is the first approved applicant for a drug and that ANDA B has an application for
the same drug that is still pending at the time ANDA A is approved. ANDA A then begins commercial marketing,
triggering the CGT exclusivity period. During the CGT exclusivity period, ANDA B becomes ready for approval,
but is blocked by ANDA A’s CGT exclusivity. The applicant for ANDA A agrees to a selective waiver to ANDA
B, allowing for approval of ANDA B. The applicant for ANDA B may then utilize the remaining portion of the
CGT exclusivity period.

If a first approved applicant’s CGT exclusivity were triggered and selectively waived in favor of an applicant with
an unapproved ANDA, the fact of the selective waiver in favor of the other applicant could be considered
information in an unapproved ANDA. As such, FDA generally would not disclose that the selective waiver had
occurred to anyone except the applicant in whose favor CGT exclusivity was waived, at least until the ANDA
benefited by the waiver was approved. See 21 CFR 314.430(d)(1).

Section 505(j)(5)(D)(iv) of the FD&C Act.

Contains Nonbinding Recommendations
must both obtain approval of and promptly market its product(s) in order to enjoy the benefits of
CGT exclusivity.
FDA interprets this language to mean that the first approved applicant will forfeit eligibility for
CGT exclusivity if the applicant fails to market within 75 days, beginning on the calendar day
after the date on which approval of the first approved applicant’s application for the CGT is
made effective, and not the date of approval itself. FDA further interprets this language to mean
that a first approved applicant forfeits only its own eligibility for CGT exclusivity and such
forfeiture does not affect the eligibility of any other first approved applicants. For example,
assume the applicants for ANDA A and ANDA B are both first approved applicants. The
applicant for ANDA A forfeits its eligibility for CGT exclusivity for failure to market within 75
days after the date of approval, but the applicant for ANDA B markets within 75 days after the
date of approval and thus maintains its eligibility for CGT exclusivity. In such case, ANDA B
would trigger the 180-day CGT exclusivity. Because ANDA A was approved prior to ANDA B
triggering the 180-day CGT exclusivity, the applicant for ANDA A could market its CGT during
the 180-day CGT exclusivity period (and thus benefit from ANDA B’s exclusivity), even though
the applicant for ANDA A forfeited its own eligibility for CGT exclusivity.
In the event that all first approved applicants forfeit their eligibility for CGT exclusivity, the
CGT exclusivity is extinguished. The CGT exclusivity is only available to those ANDA
applicants that meet the statutory definition of a first approved applicant, and the exclusivity
does not roll to the next approved ANDA following forfeiture by all first approved applicants. 69
E.

First Commercial Marketing

The first approved applicant’s first commercial marketing determines whether (and when) the
180-day CGT exclusivity period under section 505(j)(5)(B)(v) of the FD&C Act begins and
whether that first approved applicant has forfeited its eligibility for exclusivity under section
505(j)(5)(D)(iv). 70 FDA generally would not be aware of first commercial marketing by a first
approved applicant unless the first approved applicant notified FDA of the commencement of
such marketing. 71
Because the orderly operation of the 180-day CGT exclusivity period under section
505(j)(5)(B)(v)(I) of the FD&C Act and the forfeiture provision under section 505(j)(5)(D)(iv)
69

See section 505(j)(5)(B)(v)(II) and 505(j)(5)(B)(v)(III)(bb)(AA) of the FD&C Act.

See generally 21 CFR 314.3(b) (“Commercial marketing is the introduction or delivery for introduction into
interstate commerce of a drug product described in an ANDA, outside the control of the ANDA applicant, except
that the term does not include transfer of the drug product for investigational use under part 312 of this chapter or
transfer of the drug product to parties identified in the ANDA for reasons other than sale. Commercial marketing
includes the introduction or delivery for introduction into interstate commerce of the reference listed drug by the
ANDA applicant.”).

FDA’s regulations and the statute do not require that a first approved applicant provide FDA with notification of
the first commercial marketing of a competitive generic therapy. FDA’s regulations at 21 CFR 314.107(c)(2) require
that a “first applicant” (as defined in section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act) provide FDA with notice
within 30 days of the first applicant’s first commercial marketing. However, this requirement is limited only to a
first applicant and does not apply to a first approved applicant, which is an ANDA applicant eligible for CGT
exclusivity under section 505(j)(5)(B)(v) of the FD&C Act.

Contains Nonbinding Recommendations
requires that FDA know when first approved applicant(s) has commenced first commercial
marketing, we (1) will assume, for approval purposes, that no holder of CGT exclusivity has
begun commercial marketing, and thus that no CGT exclusivity blocks approval of a subsequent
ANDA, unless the first approved applicant provides FDA with written notification confirming
that it has commenced commercial marketing of the CGT and (2) will assume that CGT
exclusivity has been forfeited and thus would not block a subsequent approval if the first
approved applicant has not provided FDA with written notification within the 75-day period
confirming that it has commenced commercial marketing of the CGT.
To ensure that FDA receives timely notification of first commercial marketing, FDA
recommends that the first approved applicant submit a general correspondence to the ANDA
informing FDA that it has commenced marketing, with a duplicate copy of this correspondence
submitted to the Office of Generic Drug’s Patent and Exclusivity Team at
[email protected].
F.

Relationship Between CGT Exclusivity and 180-Day Patent Challenge
Exclusivity

The CGT exclusivity period described at section 505(j)(5)(B)(v) and the 180-day patent
challenge exclusivity period described at section 505(j)(5)(B)(iv), while sharing some basic
structural similarities, are separate exclusivity schemes with their own specific eligibility criteria
that generally function independently of each other. As noted above, the intent of each
exclusivity is different, as 180-day patent challenge exclusivity provides an incentive to generic
drug applicants to be the first to expose themselves to the risk of patent infringement litigation,
which could enable generic drugs to be approved prior to patent expiry. CGT exclusivity
provides an incentive to generic drug applicants to undertake the work to obtain the first
approval of and promptly market drugs that had inadequate competition (and for which there
were no unexpired patents or exclusivities listed in the Orange Book at the time of submission).
Although CGT exclusivity and 180-day patent challenge exclusivity remain distinct
exclusivities, Congress included some limitations on an ANDA applicant’s eligibility for CGT
exclusivity related to 180-day patent challenge exclusivity for the applicable drug. Specifically,
as noted earlier, the definition of first approved applicant in the CGT exclusivity provisions of
the statute specifies that a potential first approved applicant must not: (1) otherwise be eligible
for 180-day patent challenge exclusivity “for the drug that is the subject of the application for the
competitive generic therapy” 72 or (2) have submitted an ANDA “for a drug for which all drug
versions have forfeited eligibility for [180-day exclusivity]” under section 505(j)(5)(B)(iv)
pursuant to section 505(j)(5)(D). 73
With respect to the first eligibility limitation described above, FDA interprets this limitation to
mean that a potential first approved applicant for a particular drug must not otherwise be eligible

See section 505(j)(5)(B)(v)(III)(bb)(BB) of the FD&C Act.

See section 505(j)(5)(B)(v)(III)(bb)(CC) of the FD&C Act.

Contains Nonbinding Recommendations
for 180-day patent challenge exclusivity for the same drug. 74 In most cases, a potential first
approved applicant that otherwise meets the criteria for CGT exclusivity will not be excluded as
a result of this limitation, as eligibility for CGT exclusivity requires that there be no unexpired
patents listed in the Orange Book at the time of submission. 75 In contrast, eligibility for 180-day
patent challenge exclusivity requires, among other things, the submission of a patent certification
asserting that a patent listed in the Orange Book is invalid, unenforceable, or will not be
infringed. 76
With respect to the second eligibility limitation described above, FDA interprets this limitation to
mean that a potential first approved applicant’s ANDA for a particular drug cannot be for a drug
for which another ANDA applicant or applicants were eligible for 180-day patent challenge
exclusivity and for which all such ANDA applicants have forfeited eligibility for 180-day patent
challenge exclusivity. 77 This means that, for example, if prior to a potential first approved
applicant’s submission of its ANDA, other ANDA applicants for the same drug were eligible for
180-day patent challenge exclusivity but all such applicants forfeited their eligibility for 180-day
patent challenge exclusivity, the potential first approved applicant would not qualify as a first
approved applicant for the purposes of CGT exclusivity, even if the potential first approved
applicant submitted its ANDA several years after the relevant forfeiture of the 180-day patent
challenge exclusivity.
Given the different eligibility criteria for each exclusivity, CGT exclusivity and 180-day patent
challenge exclusivity generally do not overlap in terms of timing or scope. However, there may
be limited circumstances in which multiple ANDA applicants potentially are eligible for either
CGT exclusivity or 180-day patent challenge exclusivity for the same drug at the same time. This
could occur in the event that there are no patents or exclusivities listed in the Orange Book for a
particular RLD at the time the original ANDA is submitted for a drug that has been designated as
a CGT, but the holder of the NDA for the RLD later lists a patent for which other ANDA
applicants first submit paragraph IV certifications to the relevant listed patent.
For example, assume that the applicant for ANDA C and the applicant for ANDA D are seeking
approval of the same drug and each submits a substantially complete ANDA to FDA. Both
ANDA C and ANDA D cover drugs that have been designated as CGTs consistent with section
506H(b)(3) of the FD&C Act.
ANDA C is submitted first and ANDA D is submitted one week after ANDA C. After ANDA C
is submitted but before ANDA D is submitted, the NDA holder for the RLD timely lists a patent
in the Orange Book for the RLD. ANDA D is submitted on the next day and includes a

See section 505(j)(5)(B)(v)(III)(bb)(BB) of the FD&C Act.

See section 505(j)(5)(B)(v)(III)(aa)(BB) of the FD&C Act.

See section 505(j)(5)(B)(iv)(I) of the FD&C Act, see also section505(j)(2)(A)(vii) of the FD&C Act and 21 CFR
314.94(a)(12)(i)(A).

Section 505(j)(5)(B)(v)(III)(bb)(CC) of the FD&C Act.

Contains Nonbinding Recommendations
paragraph IV certification to the relevant listed patent. 78 The day after ANDA D is submitted,
ANDA C is amended to include a paragraph IV certification to the same listed patent. In this
scenario, the ANDA C applicant may qualify as a potential first approved applicant (for purposes
of CGT exclusivity) because there were no unexpired patents or exclusivities at the time the
ANDA was submitted to FDA and because ANDA C would not be eligible for 180-day patent
challenge exclusivity. The applicant for ANDA D could qualify as a first applicant (for purposes
of 180-day patent challenge exclusivity) because, among other things, it was the first applicant to
submit a substantially complete ANDA containing a paragraph IV certification to a listed patent.
Because there may be multiple ANDA applicants that are eligible for either CGT exclusivity or
180-day patent challenge exclusivity for the same drug at the same time, questions exist as to
how the two exclusivity schemes operate concurrently. As a practical matter, the potential for
conflict is avoided because no applicant would be eligible for CGT exclusivity, as described
above, until the CGT application is approved.
For 180-day patent challenge exclusivity, on the other hand, the statute restricts FDA from
approving subsequent applicants’ ANDAs (i.e., non-first applicant ANDAs that have submitted a
paragraph IV certification to the relevant patent(s)) until (1) all first applicants have forfeited
their eligibility for 180-day patent challenge exclusivity, or (2) the 180-day patent challenge
exclusivity period has been triggered and run, or (3) the 180-day patent challenge exclusivity has
been relinquished or waived. 79 Consequently, FDA generally could not approve ANDAs,
including those ANDAs potentially eligible for CGT exclusivity, until one of these events has
occurred.
If one of these events has occurred, an ANDA potentially eligible for CGT exclusivity could be
fully approved. If all first applicants had forfeited eligibility for 180-day patent challenge
exclusivity, no CGT exclusivity would be available. Otherwise, if the date of the approval
constituted the first day on which any ANDA for such CGT is approved, the relevant 180-day
CGT exclusivity period could be triggered if the first approved applicant commences marketing
within 75 days after the date of approval. 80 Under such circumstances, CGT exclusivity and 180day patent challenge exclusivity would not overlap and could be triggered in a sequential
fashion.
For example, assume that the applicants for ANDA X and ANDA Y submit applications that
reference the same RLD but are submitted on different dates with ANDA Y being submitted on a
date after ANDA X. The applicant for ANDA X received a CGT designation for the drug in its
application and is potentially eligible for CGT exclusivity. Because, among other things, ANDA
Y challenges a patent that was listed after ANDA X is submitted, ANDA Y is determined to be
eligible for 180-day patent challenge exclusivity.

In this example, ANDA D would not qualify for CGT exclusivity due to the existence of unexpired patents listed
in the Orange Book for its RLD at the time of submission.

See section 505(j)(5)(B)(iv)(I) of the FD&C Act.

See section 505(j)(5)(B)(v)(I) and 505(j)(5)(B)(v)(III)(bb) of the FD&C Act.

Contains Nonbinding Recommendations
Subsequently, FDA determines that ANDA X meets the substantive requirements for approval,
though ANDA Y is still undergoing review by FDA and has not forfeited eligibility for 180-day
patent challenge exclusivity. In this case, FDA generally could only tentatively approve ANDA
X due to ANDA Y’s continued eligibility for 180-day patent challenge exclusivity. However,
once the 180-day patent challenge exclusivity period had been triggered and run, or
relinquished/waived, ANDA X could be fully approved and potentially trigger its own 180-day
CGT exclusivity period.
G.

Procedural Questions Regarding CGT Exclusivity Determinations

FDA will generally make decisions on exclusivity in the context of specific ANDAs that are
otherwise eligible for approval (i.e., when a potential first approved applicant’s ANDA or other
non-first-approved applicant’s ANDA is ready for approval). When FDA makes an approval
decision for an ANDA, it will inform the applicant affected by exclusivity of its status. For
example, for CGT exclusivity, FDA will generally include information in its action letter to the
ANDA applicant to inform the applicant that it is (1) a first approved applicant that is eligible for
180 days of CGT exclusivity or (2) eligible only for a tentative approval because one or more
first approved applicants are eligible for CGT exclusivity and have triggered the 180-day CGT
exclusivity period.

File Type	application/pdf
File Title	Guidance for Industry: Competitive Generic Therapies
Author	FDA/CDER
File Modified	2023-10-24
File Created	2022-10-04