Guidance for Industry 180-Day Exclusivity: Questions and Answers

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Guidance for Industry
180-Day Exclusivity:
Questions and Answers
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of
publication in the Federal Register of the notice announcing the availability of the draft
guidance. Submit electronic comments to http://www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the
docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document, contact (CDER) Harry Schwirck 301-796-4271; or
Office of Communication, Outreach and Development, Center for Biologics Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, rm.3128,
Silver Spring, MD 20993-0002, 800-835-4709 or 240-402-8010.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
January 2017
Generic Drugs

Guidance for Industry
180-Day Exclusivity:
Questions and Answers
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
and/or
Office of Communication, Outreach and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Bldg. 71, Room 3128
Silver Spring, MD 20993-0002
Phone: 800-835-4709 or 240-402-8010
Email: ocod@fda.hhs.gov
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
January 2017
Generic Drugs

Contains Nonbinding Recommendations
Draft — Not for Implementation
Table of Contents
I. 	INTRODUCTION................................................................................................................. 1
II. 	BACKGROUND ................................................................................................................... 1
A. 	ANDA APPROVAL P ATHWAY ............................................................................................. 2
B. 	P ATENT C ERTIFICATION AND 180-DAY EXCLUSIVITY…………………………...…………3
III. QUESTIONS AND ANSWERS ........................................................................................... 5
A. 	APPLICABLE S TATUTORY S CHEME………………………………………………………....5
B. 	F IRST APPLICANTS ............................................................................................................... 6
C. 	180-DAY EXCLUSIVITY AND P ATENTS ............................................................................... 10
D. 	180-DAY EXCLUSIVITY T RIGGER AND S COPE OF 180-DAY EXCLUSIVITY .......................... 11
E. 	180-DAY EXCLUSIVITY R ELINQUISHMENT AND W AIVER ................................................... 14
F. 	FORFEITURE OF 180-DAY EXCLUSIVITY ............................................................................. 14
G. 	P ROCEDURAL Q UESTIONS R EGARDING 180-DAY EXCLUSIVITY DETERMINATIONS ........... 26

Contains Nonbinding Recommendations
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Guidance for Industry	1
180-Day Exclusivity: Questions and Answers1
2
3
4
This draft guidance, when finalized, will represent the current thinking of the Food and Drug	5
Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not	6
binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the	7
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible	8
for this guidance as listed on the title page.	9
10
11
12
13
I. 	INTRODUCTION	14
15
This guidance is intended to address questions that have been raised about the provisions of the	16
Federal Food, Drug, and Cosmetic Act (FD&C Act) that relate to generic drug exclusivity, which	17
commonly is known as 180-day exclusivity for generic drug products. As a general matter, the	18
Food and Drug Administration (FDA or the Agency) has implemented these statutory provisions	19
within the context of application-specific decisions. Some FDA decisions have been made	20
publicly available (e.g., in FDA citizen petition responses and documents released in litigation).	21
In addition, in certain circumstances where a novel issue of interpretation was raised by a	22
particular factual scenario regarding forfeiture of 180-day exclusivity, FDA has opened a public	23
docket or otherwise sought comment from affected parties in advance of taking an action. Also,	24
in certain instances, applicants have submitted correspondence to their abbreviated new drug	25
applications (ANDAs) regarding 180-day exclusivity, which FDA has considered in making	26
decisions. FDA believes that a guidance for industry that provides answers to commonly asked	27
questions about 180-day exclusivity would enhance transparency and facilitate the development,	28
approval, and timely marketing of generic drug products. FDA intends to update this guidance	29
to include additional questions and answers (Q&As) as appropriate.	30
31
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.	32
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only	33
as recommendations, unless specific regulatory or statutory requirements are cited. The use of	34
the word should in Agency guidances means that something is suggested or recommended, but	35
not required.	36
37
II. 	BACKGROUND	38
39
The Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman	40
Amendments)2 to the FD&C Act established the ANDA approval pathway for generic drugs.3 In	41
1 This guidance has been prepared by the Office of Generic Drug Policy in the Center for Drug Evaluation and
Research at the Food and Drug Administration.
2 Public Law 98-417.

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2003, Congress enacted the Medicare Prescription Drug, Improvement, and Modernization Act	42
of 2003 (MMA),4 which, among other things, substantially revised certain statutory provisions	43
related to 180-day exclusivity. In this guidance, we will discuss 180-day exclusivity as it	44
pertains to ANDAs subject to the MMA statutory provisions. This guidance does not discuss	45
180-day exclusivity as it pertains to ANDAs subject to the pre-MMA statutory provisions. In	46
Section III.A, we describe how to determine which statutory scheme applies to a particular	47
ANDA.	48
49
A. 	ANDA Approval Pathway	50
51
The process for obtaining approval to market an innovator drug approved under a new drug	52
application (NDA) differs from that for obtaining approval to market a generic drug under an	53
ANDA. A sponsor of an innovator drug must submit an NDA, which must contain, among other	54
things, a demonstration of the safety and effectiveness of the drug for the conditions of use for	55
which approval is sought.5 In its application, an NDA applicant must submit information for	56
each patent that claims the drug or method of using the drug and for which a claim of patent	57
infringement could reasonably be asserted against a person engaged in the unlicensed	58
manufacture, use, or sale of the drug product.6 Upon approval of an NDA, FDA publishes this	59
patent information in its publication Approved Drug Products with Therapeutic Equivalence	60
Evaluations, known as the Orange Book.7
61
62
To obtain approval of a generic drug, an ANDA applicant is not required to provide independent	63
evidence of the safety and effectiveness of the proposed generic drug. Instead, the applicant	64
relies on FDA’s previous finding that the reference listed drug (RLD)8 relied upon by the ANDA	65
applicant is safe and effective. The ANDA applicant must identify the RLD on which it seeks to	66
rely and, among other things, demonstrate, with limited exceptions, that the proposed generic	67
drug has the same active ingredient(s), route of administration, dosage form, and strength as the	68
RLD.9 A generic drug also must have the same conditions of use and the same labeling as the	69
RLD (except for certain permissible labeling differences),10 and the applicant must demonstrate	70
that its proposed generic drug is bioequivalent to the RLD.11
71
3 For the purpose of this guidance, the term generic drug refers to a new drug product for which approval is sought
or has been obtained in an ANDA submitted under section 505(j) of the FD&C Act.
4 Public Law 108-173.
5 Section 505(b)(1) of the FD&C Act.
6 Id. See also section 505(c)(2) of the FD&C Act.
7 The Orange Book is available at http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm.
8 An RLD is the listed drug identified by FDA as the drug product on which an ANDA applicant relies in seeking
approval of its ANDA. 21 CFR 314.3(b).
9 A generic drug with the same active ingredient, dosage form, route of administration, and strength as the RLD is
considered pharmaceutically equivalent to that product. See also 21 CFR 314.3(b).
10 See section 505(j)(2)(A)(i), (v) of the FD&C Act. An example of a permissible difference in labeling would be a
difference when an ANDA applicant is not seeking approval for a use protected by patent or exclusivity pursuant to
section 505(j)(2)(A)(viii) of the FD&C Act and 21 CFR 314.94(a)(8)(iv).
11 See section 505(j)(2)(A)(iv) of the FD&C Act. Therapeutically equivalent products are approved drug products
that are pharmaceutical equivalents for which bioequivalence has been demonstrated, and that can be expected to
have the same clinical effect and safety profile when administered to patients under the conditions specified in the
labeling. 21 CFR 314.3(b).

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72
B. 	Patent Certification and 180-day Exclusivity	73
74
The timing of ANDA approval depends on, among other things, the patent and exclusivity	75
protections for the RLD. An applicant must provide in its ANDA additional information related	76
to any patents for the RLD. In particular, the ANDA applicant generally must submit to FDA	77
one of four specified certifications regarding the patents for the RLD under section	78
505(j)(2)(A)(vii) of the FD&C Act.	79
80
If the Orange Book does not list a patent for the RLD, the ANDA applicant must certify:	81
82
1. 	That such patent information has not been submitted by the NDA holder for listing in the	83
Orange Book (a paragraph I certification).12
84
85
With respect to each patent listed in the Orange Book for the RLD, the applicant’s patent	86
certification must state one of the following:	87
88
2. 	That such patent has expired (a paragraph II certification)	89
3. 	The date on which such patent will expire (a paragraph III certification)	90
4. 	That such patent is invalid, unenforceable, or will not be infringed by the manufacture,	91
use, or sale of the new drug for which the application is submitted (a paragraph IV	92
certification).13
93
94
If an applicant submits a paragraph I or II certification, the patent in question will not delay	95
ANDA approval. If an applicant submits a paragraph III certification, the applicant agrees to	96
wait until the relevant patent has expired before seeking final approval of its ANDA. If,	97
however, an applicant wishes to seek approval of its ANDA before a listed patent has expired by	98
challenging the validity of a patent, claiming that a patent would not be infringed by the product	99
proposed in the ANDA, or claiming a patent is unenforceable, the applicant must submit a	100
paragraph IV certification to FDA.	101
102
The FD&C Act describes only one circumstance in which an ANDA applicant need not certify to	103
a listed patent. Specifically, when a patent is listed only for a method of use, an ANDA	104
applicant seeking to omit that approved method of use from the generic drug’s labeling can	105
submit a section viii statement, acknowledging that a given method-of-use patent has been listed,	106
but stating that the patent at issue does not claim a use for which the applicant seeks approval.14
107
108
An applicant submitting a paragraph IV certification to a listed patent must provide the NDA	109
holder and each patent owner notice of its paragraph IV certification, including a description of	110
the legal and factual basis for the ANDA applicant’s assertion that the patent is invalid,	111
12 21 CFR 314.94(a)(12)(i)(A). If in the opinion of the ANDA applicant and to the best of its knowledge there are
no patents claiming the drug product, drug substance, or method of use of the drug product, the applicant must
submit to its ANDA a certification stating that opinion. 21 CFR 314.94(a)(12)(ii).
13 Section 505(j)(2)(A)(vii) of the FD&C Act; see also 21 CFR 314.94(a)(12)(i)(A).
14 See section 505(j)(2)(A)(viii) of the FD&C Act. See also 21 CFR 314.94(a)(12)(iii).

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unenforceable, or will not be infringed.15 If a patent is listed at the time an ANDA is submitted	112
and, in response to notice of a paragraph IV certification, the NDA holder or patent owner	113
initiates a patent infringement action against the ANDA applicant within 45 days of receiving the	114
required notice, approval of the ANDA generally will be stayed for 30 months from the later of	115
the date of receipt of the notice by any owner of the patent or the NDA holder or such shorter or	116
longer time as the court might order.16 If a patent is listed in the Orange Book after an ANDA is	117
submitted but before it is approved, the applicant for the pending ANDA generally must amend	118
its application and provide an appropriate patent certification or statement to the newly listed	119
patent; however, no 30-month stay will be available in this circumstance.17
120
121
The statute provides an incentive and a reward to generic drug applicants that expose themselves	122
to the risk of patent litigation. It does so by granting a 180-day period of exclusivity vis-à-vis	123
certain other ANDA applicants to the applicant that is first to file a substantially complete	124
ANDA containing a paragraph IV certification to a listed patent. If only one such ANDA is filed	125
on the first day, there is only one first applicant; if two or more such ANDAs are filed on the	126
first day, the ANDA applicants share first-applicant status.18 If an ANDA contains a paragraph	127
IV certification for a relevant patent and the ANDA is not that of a first applicant, the ANDA	128
applicant is regarded as a subsequent applicant.19
129
130
If an ANDA meets the substantive requirements for approval, but cannot be finally approved due	131
to unexpired patents or exclusivities, FDA will tentatively approve the ANDA. Tentative	132
approval “means notification to an applicant by [FDA] that an [ANDA] meets the requirements	133
of [section 505(j)(2)(A) of the FD&C Act] but cannot receive effective approval because the	134
application does not meet the requirements of this subparagraph, there is a period of exclusivity	135
for the listed drug under subparagraph (F) or section 505A, or there is a 7-year period of	136
exclusivity for the listed drug under section 527.”20
137
138
The FD&C Act describes a number of conditions under which an ANDA applicant may forfeit	139
eligibility for 180-day exclusivity. These forfeiture events can be generally described as: (1)	140
failure to market; (2) withdrawal of application; (3) amendment of certification; (4) failure to	141
obtain tentative approval; (5) entry into agreement with another applicant, the listed drug	142
15 Section 505(j)(2)(B) of the FD&C Act.
16 Section 505(j)(5)(B)(iii) of the FD&C Act and 21 CFR 314.107(b)(3)(i).
17 Id. See also 21 CFR 314.94(a)(12)(vi).
18 As described in Question 2, an applicant that submitted a substantially complete ANDA without a paragraph IV
certification may become eligible for 180-day exclusivity by amending its application to contain a paragraph IV
certification to a listed patent on the first day that an ANDA or amendment containing a paragraph IV certification is
submitted for that RLD.
19 See section 505(j)(5)(B)(iv)(I), (II)(aa) and 505(j)(5)(D)(iii) of the FD&C Act. See also 21 CFR 314.107(c)(1);
Abbreviated New Drug Applications and 505(b)(2) Applications; Final Rule, 81 FR 69580, 69627-69628 (Oct. 6,
2016).
20 Section 505(j)(5)(B)(iv)(II)(dd)(AA) of the FD&C Act. See also 21 CFR 314.3(b) (defining tentative approval to
also include, among other things, notification that an ANDA otherwise meets the requirements for approval under
the FD&C Act, but cannot be approved because there is a period of exclusivity for the listed drug under section
505E of the FD&C Act, or because a court order pursuant to 35 U.S.C. 271(e)(4)(A) orders that the ANDA may be
approved no earlier than the date specified) and 21 CFR 314.105.

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application holder, or a patent owner; and (6) expiration of all patents.21 Under these provisions,	143
if certain events occur, an applicant eligible for 180-day exclusivity at the time its ANDA was	144
submitted (first applicant) may forfeit eligibility for 180-day exclusivity. If all first applicants	145
forfeit their eligibility for 180-day exclusivity, no applicant will be eligible for 180-day	146
exclusivity, and FDA may approve subsequent applicants’ ANDAs, subject to the approval	147
requirements of the FD&C Act.	148
149
FDA has received a number of questions about 180-day exclusivity and has identified the	150
following commonly asked questions for inclusion in this guidance. FDA expects the following	151
information to enhance transparency and facilitate the development, approval, and timely	152
marketing of generic drugs. FDA intends to update this guidance to include additional Q&As as	153
appropriate.	154
155
III. 	QUESTIONS AND ANSWERS	156
157
A. 	Applicable Statutory Scheme	158
159
Q1. 	How does FDA determine whether the pre-MMA or MMA provisions of the FD&C	160
Act apply to a particular ANDA?	161
162
Section 1102(b)(1) of the MMA provides that the MMA 180-day exclusivity provisions are	163
effective only with respect to an ANDA filed after the date of enactment (i.e., December 8, 2003)	164
for a listed drug for which no paragraph IV certification was made before that date.22 The	165
following list illustrates how FDA has applied this effective date provision in particular	166
situations:	167
168
• 	If all ANDAs referencing a particular RLD are submitted to FDA after December 8, 2003	169
(and thus no paragraph IV certification could have been submitted before December 8,	170
2003), the MMA 180-day exclusivity provisions apply to all of the ANDAs.	171
• 	If at least one ANDA with a paragraph IV certification to a listed patent for the RLD was	172
submitted before December 8, 2003, all ANDAs referencing that RLD (including	173
ANDAs submitted after December 8, 2003) are governed by the pre-MMA statutory	174
provisions.	175
• 	If one or more ANDAs referencing a particular RLD were submitted before December 8,	176
2003, but the first paragraph IV certification was submitted after December 8, 2003, the	177
pre-MMA provisions govern for any ANDA referencing that RLD (whether or not that	178
particular ANDA was filed before or after December 8, 2003), because section	179
1102(b)(1) of the MMA is based on the date of submission of the first application, not on	180
the date of the first paragraph IV certification.	181
FDA has concluded that the effective date provision imposes the same statutory scheme on all	182
ANDAs referencing a specific RLD. An attempt by FDA to apply both pre-MMA and MMA	183
21 Section 505(j)(5)(D) of the FD&C Act.
22 Section 1102(b)(1) of the MMA.

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statutory schemes to a single group of applications with a common RLD could result in conflict	184
between the MMA and pre-MMA provisions. The eligibility, triggering, and forfeiture features	185
of the different 180-day exclusivity schemes could render one applicant ineligible for exclusivity	186
while another applicant could retain its eligibility. To avoid these inequitable outcomes, all	187
ANDAs submitted referencing the same RLD will be subject to one statutory scheme.	188
189
B. 	First Applicants	190
191
Q2. 	How does an ANDA applicant qualify as a “first applicant”?	192
193
A first applicant is an ANDA “applicant that, on the first day on which a substantially complete	194
application containing a [paragraph IV] certification … is submitted for approval of a drug,	195
submits a substantially complete application that contains and lawfully maintains a [paragraph	196
IV] certification … for the drug.”23
197
198
An applicant that previously submitted a substantially complete ANDA that did not contain a	199
paragraph IV certification may become eligible for 180-day exclusivity by amending its ANDA	200
to contain a paragraph IV certification to a listed patent for the RLD on the first day that an	201
ANDA or amendment containing a paragraph IV certification is submitted.	202
203
The listed patent or patents to which an ANDA applicant submitted a paragraph IV certification	204
that gives rise to the eligibility for 180-day exclusivity is referred to in this draft guidance as the	205
qualifying patent(s).	206
207
Q3. 	What constitutes a substantially complete application?	208
209
A substantially complete application is an ANDA that on its face is sufficiently complete to	210
permit a substantive review. Sufficiently complete means that the ANDA contains all the	211
information required under section 505(j)(2)(A) of the FD&C Act and does not contain a	212
deficiency described in 21 CFR 314.101(d) and (e).24 FDA indicates its determination that an	213
ANDA is substantially complete when the Agency receives the ANDA for review under 21 CFR	214
314.101. If FDA determines, after an initial evaluation, that an ANDA was substantially	215
complete as of the date it was submitted to FDA, FDA will consider the ANDA to have been	216
received as of the date of submission.25
217
218
Q4. 	Does an ANDA applicant have to be the first to submit a paragraph IV certification	219
to all of the RLD’s listed patents to be a first applicant?	220
221
No. The statute requires “a” paragraph IV certification;26 it does not require a first applicant to	222
be the first to submit a paragraph IV certification to more than a single patent (or all of the	223
patents), even if multiple patents are listed for the RLD.	224
23 Section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act; see also 21 CFR 314.3(b).
24 21 CFR 314.3(b); see also section 505(j)(5)(B)(iv)(II)(cc) of the FD&C Act.
25 21 CFR 314.101(b)(2).
26 Section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act.

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225
There can be multiple patents that could qualify a single ANDA applicant as a first applicant, so	226
long as they are certified to on that same first day that the first paragraph IV certification in an	227
ANDA for that RLD is submitted. As a result, each qualifying patent separately can affect	228
exclusivity. For example, if an ANDA applicant submitted paragraph IV certifications to two	229
separate patents on the same first day and the first patent expires prior to triggering of 180-day	230
exclusivity, the paragraph IV certification to the second patent can remain a basis for first-	231
applicant status and for 180-day exclusivity.	232
233
Q5. 	Can an ANDA applicant qualify as a first applicant when it includes both a	234
paragraph IV certification and a section viii statement to a single listed patent?	235
236
Yes. FDA has determined that when both drug product or drug substance claims and method-of-	237
use claims are contained within the same patent, an applicant may file a paragraph IV	238
certification with respect to the drug product or drug substance patent claim(s) and a section viii	239
statement with respect to the method-of-use claim(s) in the patent. This type of certification is	240
commonly referred to as a split certification. This approach preserves the NDA holder’s	241
statutory right to assert its patent rights regarding the drug substance or drug product claims	242
before ANDA approval while permitting the ANDA applicant to exercise its statutory right to	243
avoid infringing a method-of-use claim by seeking approval for fewer than all of the approved	244
conditions of use for the RLD. Consistent with this principle, the paragraph IV certification in a	245
split certification can qualify an applicant for first applicant eligibility.	246
247
Q6. 	Can an ANDA applicant be a first applicant if the applicant includes a paragraph	248
III certification to a patent that expires after the patent to which a paragraph IV	249
certification was submitted?	250
251
Yes. The statutory definition of “first applicant” requires “a” paragraph IV certification. The	252
statute does not require that the paragraph IV certification be to the latest expiring patent. For	253
example, a first applicant could have a paragraph IV certification to a patent expiring on January	254
1, 2020 (the only qualifying patent) and a paragraph III certification to a patent expiring on June	255
1, 2030.	256
257
Q7. 	Could the timing of sending notice of paragraph IV certification affect first	258
applicant status?	259
260
Yes. For original ANDAs, notice of paragraph IV certification must be provided on or after the	261
date on which the applicant receives a paragraph IV acknowledgment letter from FDA, but not	262
later than 20 days after the date of the postmark on the paragraph IV acknowledgment letter.27
263
The paragraph IV acknowledgment letter is a written, postmarked communication from FDA to	264
an applicant stating that the Agency has determined that an ANDA containing a paragraph IV	265
certification is sufficiently complete to permit a substantive review and has been received for	266
27 21 CFR 314.95(b)(1).

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review.28 Any notice sent before the ANDA applicant’s receipt of a paragraph IV	267
acknowledgment letter is invalid.29
268
269
For amendments containing a paragraph IV certification submitted before the ANDA has been	270
received for review (i.e., before receipt of a paragraph IV acknowledgment letter), the ANDA	271
applicant must send notice according to the timeframe described above for original ANDAs. If	272
an ANDA applicant’s notice of its paragraph IV certification is timely provided and the applicant	273
has not submitted a previous paragraph IV certification, FDA will base its determination of	274
whether the ANDA applicant is a first applicant on the date of submission of the amendment	275
containing the paragraph IV certification.30
276
277
For amendments submitted after the ANDA has been received for review (i.e., after receipt of an	278
acknowledgment letter or a paragraph IV acknowledgment letter) and supplements, notice of	279
paragraph IV certification must be provided at the same time that the amendment or supplement	280
is submitted to FDA. If notice is not sent simultaneously with an amendment or supplement,	281
FDA considers the paragraph IV certification not to be effective until notice is provided.31 For	282
example, if an ANDA applicant submitted a supplement containing a paragraph IV certification,	283
but notice of the paragraph IV certification was not provided until 30 days after the submission	284
of the supplement, FDA would evaluate whether the applicant was a first applicant based on the	285
date notice was provided, rather than the date of submission of the supplement. Thus, a delay in	286
giving notice of certain amendments or supplements could mean a later date for the paragraph IV	287
certification to become effective which could result in failure to obtain first applicant status (if	288
another applicant submits a certification that becomes effective in the interim).	289
290
Regardless of whether it is an original ANDA, an amendment, or a supplement, a paragraph IV	291
certification must not be submitted earlier than the first working day after the day the patent is	292
published in the Orange Book.32 Any notice sent before the first working day after the day the	293
patent is published in the Orange Book is invalid.33
294
295
Q8. 	What does it mean to “lawfully maintain” a paragraph IV certification?	296
297
The definition of first applicant requires that the applicant “lawfully maintain[] a [paragraph IV]	298
certification.”34 This requires an uninterrupted paragraph IV certification to the qualifying patent	299
or patent claim. For example, an applicant has not lawfully maintained its paragraph IV	300
certification if the applicant initially submits a paragraph IV certification to a patent or patent	301
claim, and then later amends its ANDA to include a paragraph III certification or a section viii	302
statement to the qualifying patent or patent claim, and then amends its ANDA again to include a	303
paragraph IV certification to the same patent or patent claim. However, if the applicant initially	304
submits a paragraph IV certification to a qualifying patent or patent claim and subsequently	305
28 See 21 CFR 314.3(b).
29 21 CFR 314.95(b)(2).
30 21 CFR 314.95(d)(2). See also 21 CFR 314.94(a)(12)(viii)(C)(1)(ii).
31 Cf. Purepac Pharmaceutical Co. v. Thompson, 354 F. 3d 877 (D.C. Cir. 2004).
32 See 21 CFR 314.94(a)(12)(viii)(C)(1)(ii).
33 See 21 CFR 314.95(b)(2).
34 Section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act and 21 CFR 314.3(b).

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submits an amendment that contains a paragraph IV certification to the same qualifying patent or	306
patent claim (and notice of the paragraph IV certification is sent in accordance with 21 CFR	307
314.95(d)), the first applicant has lawfully maintained the paragraph IV certification to the patent	308
or patent claim upon which eligibility for 180-day exclusivity is based.35
309
310
In addition, if a district court decides that the qualifying patent has been infringed (and the patent	311
is valid), and the judgment of the district court is not appealed or is affirmed, the ANDA	312
applicant’s paragraph IV certification that the patent was invalid, unenforceable, or not infringed	313
is no longer accurate. The applicant would be required to amend its ANDA to change its	314
paragraph IV certification to a paragraph III certification, which acknowledges the date the	315
patent expires.36
316
317
Q9. 	Can there be more than one first applicant for a single drug product?	318
319
Yes. The 180-day exclusivity provisions contemplate that there can be multiple first applicants.37
320
Multiple ANDAs that include paragraph IV certifications to one or more patents listed for an	321
RLD often will be submitted to FDA on the day the first such application (or the first paragraph	322
IV certification) is submitted. If multiple applicants submit paragraph IV certifications on the	323
first day that paragraph IV certifications for that RLD are submitted, all will be considered first	324
applicants. In addition, different ANDA applicants each can qualify as first applicants by	325
certifying to different listed patents on the same first day.	326
327
Q10. 	Do multiple first applicants for a single drug product each get their own 180-day	328
exclusivity period?	329
330
No. There is one 180-day exclusivity period for each drug product. Accordingly, whether	331
multiple first applicants enjoy the full 180-day exclusivity period depends on when those	332
ANDAs are approved in relation to when the 180-day exclusivity period is triggered.38
333
334
Q11. 	Can there be different first applicants for different strengths of a drug product?	335
336
Yes. Separate 180-day exclusivity periods are available for each strength of the same drug	337
product, because each strength is a distinct drug product. Thus, it is possible for there to be	338
different first applicants for different strengths of the RLD. For example, assume ANDA A	339
applicant submitted the first substantially complete application that contained a paragraph IV	340
certification for a 30 mg strength RLD and lawfully maintained that certification. A few days	341
later, ANDA B applicant submitted its ANDA containing a paragraph IV certification for the 30	342
mg strength RLD. The Agency then approves a 60 mg strength RLD, and lists a patent in the	343
Orange Book submitted by the NDA holder for that strength. ANDA B applicant amends its	344
ANDA to include the 60 mg strength and includes the first paragraph IV certification to the	345
patent listed for the 60 mg strength and lawfully maintains that certification. ANDA A applicant	346
35 81 FR 69580, 69617 (Oct. 6, 2016).
36 See 21 CFR 314.94(a)(12)(viii)(A).
37 See, e.g., section 505(j)(5)(D)(iii) of the FD&C Act (refers to “first applicants”).
38 See Question 17 below.

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similarly amends its ANDA to include the 60 mg strength, but three days later. In these	347
circumstances, ANDA A applicant is the first applicant for the 30 mg strength, and ANDA B	348
applicant is the first applicant for the 60 mg strength.	349
350
C. 	180-day Exclusivity and Patents	351
352
Q12. 	Does an ANDA applicant need to win its patent litigation to be considered a first	353
applicant that retains eligibility for 180-day exclusivity?	354
355
No. An applicant potentially may retain eligibility for 180-day exclusivity even if it is not sued	356
as a result of its qualifying paragraph IV certification or, if sued, the case is resolved, for	357
example, through settlement that allows the applicant to enter the market before the patent	358
expires.39
359
360
Q13. 	Can a patent that an NDA holder requests to remove from the Orange Book still	361
give rise to 180-day exclusivity?	362
363
Yes. An NDA holder can request that FDA remove a patent from the Orange Book in certain	364
circumstances: for example, if a court declared the patent invalid. However, if an NDA holder	365
requests that a patent be removed from the Orange Book and one or more first applicants are	366
already eligible for 180-day exclusivity based on a paragraph IV certification to that patent, FDA	367
will not remove the patent until any 180-day exclusivity stemming from the listed patent has	368
expired, or has been extinguished or relinquished.40 Until the patent is removed from the Orange	369
Book―after any associated 180-day exclusivity has expired or has been extinguished or	370
relinquished―ANDA applicants must submit or maintain appropriate certifications to the patent	371
notwithstanding the NDA holder’s request to remove the patent. This practice ensures that NDA	372
holders cannot unilaterally extinguish an ANDA applicant’s eligibility for 180-day exclusivity	373
by requesting removal of the patent from the Orange Book prior to ANDA approval.41 In such	374
circumstances, FDA will indicate in the Orange Book that the NDA holder has requested	375
removal of the patent.42
376
377
Q14. 	Does an ANDA applicant retain 180-day exclusivity after the qualifying patent	378
expires?	379
380
No. In keeping with the statutory language and purpose of 180-day exclusivity, FDA has	381
construed the statute such that 180-day exclusivity attaches based only on paragraph IV	382
certifications to unexpired patents. 	A paragraph IV certification does not survive the expiry of a	383
listed patent. Upon patent expiry, the statute and FDA’s regulations require ANDA applicants to	384
39 Cf. Mova Pharms. Corp. v. Shalala, 140 F.3d 1060 (D.C. Cir. 1998).
40 See 21 CFR 314.94(a)(12)(viii)(B); see also discussion in sections E and F of this guidance.
41 See Teva Pharms. USA, Inc. v. Sebelius, 595 F.3d 1303 (D.C. Cir. 2010); see also 21 CFR 314.53(f)(2)(i).
42 See FDA’s website on Orange Book Data Files, at
http://www.fda.gov/drugs/informationondrugs/ucm129689.htm (describing use of the patent delist request flag as
indicating that the “[s]ponsor has requested [that the] patent be delisted [but the] patent has remained listed because,
under [s]ection 505(j)(5)(D)(i) of the [FD&C] Act, a first applicant may retain eligibility for 180-day exclusivity
based on a paragraph IV certification to this patent for a certain period”).

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amend their certifications from a paragraph IV certification to a paragraph II certification, which	385
states that the patent has expired.43 If an applicant neglects to amend its certification to a	386
paragraph II certification after a patent expires, FDA will construe the application as including a	387
paragraph II certification.44 As noted above, applications with only paragraph II certifications	388
are eligible for immediate effective approval.45 Therefore, once the only qualifying patent	389
expires, there are no longer any ANDAs blocked by 180-day exclusivity.	390
391
This interpretation of the statute effectuates the goals of the Hatch-Waxman Amendments. The	392
180-day exclusivity provisions were drafted to give ANDA applicants an incentive to be the first	393
to challenge a listed patent, potentially removing that patent as a barrier to approval. Once a	394
listed patent expires and is no longer a barrier to ANDA approval, there is no longer a need to	395
provide an incentive to challenge it in court. Thus, an expired patent does not serve as the basis	396
for a 180-day exclusivity award, and 180-day exclusivity does not extend beyond the life of the	397
patent.	398
399
D. 	180-day Exclusivity Trigger and Scope of 180-Day Exclusivity	400
401
Q15. 	How is 180-day exclusivity triggered?	402
403
The FD&C Act provides that the 180-day exclusivity period is triggered by “first commercial	404
marketing of the drug (including the commercial marketing of the listed drug) by any first	405
applicant.”46 FDA has interpreted the statutory phrase “including the commercial marketing of	406
the listed drug” to provide that exclusivity can be triggered by the marketing of an authorized	407
generic47 by a first applicant, even if that first applicant’s ANDA has not yet been approved.	408
409
Concluding that 180-day exclusivity is triggered upon the first applicant’s commercial marketing	410
of an authorized generic or the RLD prevents potential subversion of the statutory scheme	411
through collusion between NDA holders and first applicants. If 180-day exclusivity were	412
triggered only by commercially marketing the first applicant’s ANDA product, a first applicant	413
that struck a deal with the NDA holder to commercially market the authorized generic or RLD	414
43 Section 505(j)(2)(A)(vii)(II), (IV); 21 CFR 314.94(a)(12)(viii)(C)(1)(i) (“An applicant must amend a submitted
certification or statement if, at any time before the date of approval of the ANDA, the applicant learns that the
submitted certification or statement is no longer accurate”).
44 81 FR 69580, 69615 (Oct. 6, 2016).
45 Section 505(j)(2)(A)(vii)(II); (j)(5)(B)(i) (when an applicant submits only a paragraph II certification, approval of
the applicant’s ANDA “may be made effective immediately”); 21 CFR 314.94(a)(12)(viii).
46 Section 505(j)(5)(B)(iv)(I) of the FD&C Act; see also 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.”).
47 Section 505(t)(3) of the FD&C Act defines an authorized generic as “a listed drug (as that term is used in
subsection (j)) that: (A) has been approved under subsection (c); and (B) is marketed, sold, or distributed directly or
indirectly to retail class of trade under a different labeling, packaging (other than repackaging as the listed drug in
blister packs, unit doses, or similar packaging for use in institutions), product code, labeler code, trade name, or
trade mark than the listed drug.” See also 21 CFR 314.3(b).

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instead of marketing the product described in its ANDA potentially could block approval of	415
subsequent ANDAs until patent expiration.	416
417
Q16. 	Once triggered, can 180-day exclusivity be suspended or postponed?	418
419
Once triggered, the 180-day period runs without interruption.	420
421
Q17. 	How does the trigger of the 180-day exclusivity period by one first applicant affect	422
other first applicants?	423
424
The effect of one first applicant’s trigger of the 180-day exclusivity period on other first	425
applicants flows from the fact that there is only one exclusivity period available for each drug	426
product (see Question 10 above). Any first applicant’s trigger of the exclusivity period triggers	427
the 180-day exclusivity period for all first applicants for that drug product and exclusivity for all	428
first applicants ends 180 days after the initial trigger. Other first applicants will benefit from	429
exclusivity only to the extent they commercially market during this exclusivity period. The	430
following examples illustrate how shared 180-day exclusivity might operate. Assume ANDA A,	431
ANDA B, and ANDA C all qualified as first applicants.	432
433
• 	If all three ANDAs are approved on the same day, and if all three first commercially	434
market that same day, triggering the exclusivity period, all three applicants benefit from	435
the full 180-day exclusivity period.	436
• 	If all three ANDAs are approved on the same day, but only ANDA A is commercially	437
marketed on that first day triggering the exclusivity period, it is triggered for all three	438
ANDAs. Thus, if ANDA B is not commercially marketed until day 30, that applicant	439
will benefit from exclusivity only for the remainder of the 180-day period (i.e., 150 days).	440
If ANDA C is not commercially marketed until day 179, it will benefit from only one day	441
of exclusivity.	442
• 	If one or more ANDAs are approved on the same day, but one or more applicants first	443
commercially market the drug product 60 days after approval, the 180-day exclusivity	444
period is triggered upon commercial marketing and runs for 180 days.	445
446
Q18. 	Does 180-day exclusivity block approval of all ANDAs that reference the same	447
RLD?	448
449
No. 180-day exclusivity blocks only the approval of subsequent ANDAs that also contain a	450
paragraph IV certification.48 There are several examples in which 180-day exclusivity does not	451
block approval of another ANDA referencing the same RLD:	452
453
• 	If an ANDA was approved before the NDA holder submitted a patent that provides the	454
basis for first applicant status for a pending ANDA, any related 180-day exclusivity	455
would not affect the previously approved ANDA.	456
48 See section 505(j)(5)(B)(iv)(I) of the FD&C Act.

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• 	If an ANDA applicant seeks to omit the approved method(s) of use covered by a listed	457
patent with a section viii statement, another ANDA applicant’s paragraph IV certification	458
to that same patent, and any related 180-day exclusivity, would not block approval of the	459
ANDA that contained the section viii statement.	460
• 	If a patent was late-listed vis-à-vis a pending ANDA under FDA’s regulations, a first	461
applicant’s paragraph IV certification to that patent, and any related 180-day exclusivity,	462
would not block approval of the ANDA for which the patent is late-listed and for which	463
as a result no patent certification was required.49
464
465
Q19. 	Can an authorized generic be marketed during the 180-day exclusivity period?	466
467
Yes. 180-day exclusivity only blocks approval of subsequent applicants’ ANDAs under section	468
505(j) of the FD&C Act and does not affect the approval of or marketing under NDAs, including	469
marketing of authorized generics.	470
471
Q20. Can pediatric exclusivity affect the timing of approval of subsequent applicants’	472
ANDAs after the 180-day exclusivity period is triggered?	473
474
Yes. Under section 505A(b)(1)(B)(i) of the FD&C Act (addressing pediatric exclusivity), if	475
pediatric exclusivity attaches to a listed patent, the period during which an ANDA may not be	476
approved under section 505(j)(5)(B) of the FD&C Act may be extended by 6 months after the	477
date the patent expires. An ANDA with a paragraph IV certification is required to change its	478
certification to a paragraph II certification when the patent expires (and will be treated as	479
containing a paragraph II certification even if it fails to affirmatively change its certification).	480
Under section 505A(b)(1)(B)(i)(I), an ANDA that was previously blocked by another applicant’s	481
eligibility for 180-day exclusivity and that must change to a paragraph II certification (when the	482
patent that formed the basis of the exclusivity expires) will be blocked from approval by	483
pediatric exclusivity after the qualifying patent (and any associated 180-day exclusivity) has	484
expired.	485
486
For example, a first applicant’s ANDA contains a paragraph IV certification to a patent that has	487
an associated 6-month period of pediatric exclusivity. The ANDA is approved 178 days before	488
the patent expires, immediately commences commercial marketing, and enjoys 178 days of the	489
180-day exclusivity. The patent expires, all ANDAs that have not yet been approved must	490
change to paragraph II certification to that patent, the 6-month pediatric exclusivity period	491
commences, and FDA generally cannot approve any ANDA with a paragraph II certification	492
during the 6-month pediatric exclusivity period. Because the first applicant was approved prior	493
49 A late listed patent is one for which an NDA holder submits the patent for listing later than required by statute or
regulations. See, e.g., 21 CFR 314.53(d) and 21 CFR 314.94(a)(12)(vi). An applicant that submitted an ANDA for
that RLD that contained an appropriate patent certification or statement before the submission of the patent
information is not required to submit a patent certification or statement to address the patent or patent information
that is late-listed with respect to the pending ANDA. 21 CFR 314.94(a)(12)(vi). Applicants with pending ANDAs
that did not contain an appropriate patent certification or statement before the late listing of a patent or patent
information and applicants with ANDAs submitted after the patent or patent information is listed must provide an
appropriate patent certification or statement to the newly listed patent or patent information. Id.

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to the start of pediatric exclusivity, it does not need to change its certification upon patent expiry	494
and pediatric exclusivity does not affect the approval of the first applicant’s ANDA. However,	495
any subsequent applicant’s ANDA will need to contain a paragraph II certification and will not	496
be eligible for approval until the pediatric exclusivity expires. Thus, the first applicant may	497
enjoy an additional six months of de facto exclusivity before FDA can approve another ANDA.	498
499
E. 	180-day Exclusivity Relinquishment and Waiver	500
501
Q21. 	Can a first applicant relinquish or waive its 180-day exclusivity?	502
503
Yes. FDA has consistently interpreted section 505(j)(5)(B)(iv) of the FD&C Act to permit both	504
relinquishment and selective waiver of 180-day exclusivity. Relinquishment refers to the	505
voluntary and complete abandonment of eligibility for exclusivity. Selective waiver refers to a	506
first applicant’s waiver of exclusivity to permit approval during the exclusivity period of a	507
particular subsequent ANDA, or subsequent ANDAs. Relinquishment and selective waiver of	508
180-day exclusivity promote the purpose of the exclusivity―to encourage patent challenges and	509
increase marketplace competition.	510
511
A first applicant that is eligible for 180-day exclusivity may relinquish its exclusivity at any time.	512
In contrast, selective waiver of 180-day exclusivity may occur only once the exclusivity period	513
has been triggered.	514
515
Q22. 	Will subsequent applicants be notified if 180-day exclusivity is selectively waived or	516
relinquished?	517
518
As a general matter, when all first applicants have relinquished their claims to 180-day	519
exclusivity, FDA may inform subsequent applicants that are otherwise eligible for approval that	520
their ANDAs may be approved.	521
522
For selective waivers, FDA’s practice is to notify only the subsequent applicant in whose favor	523
the exclusivity has been waived. If a first applicant’s exclusivity were triggered and selectively	524
waived in favor of a subsequent applicant with an unapproved ANDA, the fact of the selective	525
waiver to the subsequent applicant could be considered information in the unapproved ANDA.	526
As such, FDA generally would not disclose that the selective waiver had occurred to anyone	527
except the applicant in whose favor exclusivity was waived, at least until the ANDA benefited by	528
the waiver was approved.50
529
530
F. 	Forfeiture of 180-day Exclusivity	531
532
Q23. 	How does FDA determine whether a first applicant has forfeited its eligibility for	533
180-day exclusivity?	534
535
To ascertain whether a first applicant has forfeited eligibility for 180-day exclusivity, FDA looks	536
at the qualifying patent(s) to determine whether the applicant has lawfully maintained its	537
50 See 21 CFR 314.430(d)(1).

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paragraph IV certification(s) and whether the applicant has forfeited exclusivity under any of the	538
forfeiture provisions, as discussed below.	539
540
1. 	Failure to Market Forfeiture Provision	541
542
Section 505(j)(5)(D)(i)(I) states that a forfeiture event occurs:	543
(I) 	If the first applicant fails to market the drug by the later of-	544
(aa) the earlier of the date that is-	545
(AA) 75 days after the date on which the approval of the application of the	546
first applicant is made effective […]; or	547
(BB) 30 months after the date of submission of the application of the first	548
applicant; or	549
(bb) with respect to the first applicant or any other applicant (which other	550
applicant has received tentative approval), the date that is 75 days after the date as	551
of which, as to each of the patents with respect to which the first applicant	552
submitted and lawfully maintained a certification qualifying the first applicant for	553
the 180-day exclusivity period […], at least one of the following has occurred:	554
(AA) In an infringement action brought against that applicant with respect	555
to the patent or in a declaratory judgment action brought by that applicant	556
with respect to the patent, a court enters a final decision from which no	557
appeal (other than a petition to the Supreme Court for a writ of certiorari)	558
has been or can be taken that the patent is invalid or not infringed.	559
(BB) In an infringement action or a declaratory judgment action described	560
in subitem (AA), a court signs a settlement order or consent decree that	561
enters a final judgment that includes a finding that the patent is invalid or	562
not infringed.	563
(CC) The patent information submitted under subsection (b) or (c) is	564
withdrawn by the holder of the application approved under subsection	565
(b).51
566
Q24. 	How does FDA determine whether a first applicant has forfeited exclusivity under	567
the “failure to market” provision?	568
569
51 Section 505(j)(5)(D)(i)(I) of the FD&C Act.

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Determining whether forfeiture has occurred requires analyzing if and when the events described	570
under the failure to market provision occurred. As seen in the statutory provision outlined	571
immediately above, application of this forfeiture provision requires a series of analyses based on	572
the timing of specific events. The statute directs that a forfeiture event occurs when the first	573
applicant fails to market the drug by the later of two dates. One of these dates is calculated under	574
item (aa) by determining the earlier of a date that is either 75 days after the first applicant’s	575
ANDA is approved (subitem (AA)) or 30 months after the date of submission of the first	576
applicant’s ANDA (subitem (BB)). The date determined under item (aa) then is compared to the	577
date as determined under item (bb). Item (bb) states that the occurrence of at least one of the	578
enumerated events with respect to a first applicant or any other applicant (which other applicant	579
has received tentative approval) as to each of the qualifying patents will begin a 75-day period	580
leading to possible forfeiture of exclusivity. These events include, very generally, when a court	581
enters a final decision that the patent is invalid or not infringed, a court signs a settlement order	582
or consent decree entering final judgment that includes a finding that the patent is invalid or not	583
infringed, or the patent information for the listed drug is withdrawn by the NDA holder.52 For an	584
event to occur under item (bb) by any other applicant, the same other applicant must receive both	585
tentative approval and a final court decision described in subitem (AA) or (BB). Forfeiture	586
under section 505(j)(5)(D)(i)(I) of the FD&C Act occurs if the first applicant fails to market by	587
the later of the dates under item (aa) or (bb).	588
589
A hypothetical example illustrates how FDA determines whether forfeiture has occurred under	590
the “failure to market” provision. For the purposes of evaluating item (aa), presume that on June	591
1, 2009, the applicant for ANDA A submitted its substantially complete application containing a	592
paragraph IV certification, which it lawfully maintained. FDA approved the ANDA on	593
December 20, 2012, and the 75-day period identified in subitem (AA) of this forfeiture provision	594
ended on March 4, 2013. Thirty months after the date the ANDA is submitted was December 1,	595
2011 (the date identified in subitem (BB)).53 The relevant date for item (aa) of the forfeiture	596
analysis is December 1, 2011, the earlier of these two dates.	597
598
For the second part of the analysis under item (bb), presume that on January 1, 2013, a court	599
entered a final decision (from which no appeal (other than a petition to the Supreme Court for a	600
writ of certiorari) has been or can be taken) that the relevant patent is invalid and not infringed in	601
an infringement action against a subsequent applicant for this RLD whose ANDA received	602
tentative approval at some point before FDA makes the forfeiture determination. The relevant	603
forfeiture date for ANDA A pursuant to subitem (AA) is March 17, 2013, 75 days after the date	604
on which the court issued its decision. Notably, this date applies even though ANDA A in this	605
example was not the subject of the litigation.	606
607
In this scenario, the failure to market forfeiture provision requires the first applicant to market by	608
March 17, 2013, the later of the dates applicable under item (aa) (December 1, 2011) and item	609
52 See Question 26 below.
53 Section 505(j)(5)(D)(i)(I)(aa)(BB) of the FD&C Act states that the 30-month period should be calculated from the
date of “submission of the application of the first applicant.” If an ANDA containing a paragraph IV certification is
“received” as substantially complete, FDA considers the date an ANDA containing a paragraph IV certification was
submitted to be the date the ANDA is “received” pursuant to 21 CFR 314.101(b).

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(bb) (March 17, 2013). In this example, if ANDA A applicant did not begin commercial	610
marketing until after March 17, 2013, it would forfeit its exclusivity.	611
612
Q25. 	Does an event from both items (aa) and (bb) of the “failure to market” provision	613
have to occur to result in forfeiture under this provision?	614
615
Yes. The “failure to market” provision results in forfeiture when there are two dates (one from	616
item (aa) and one from item (bb)) on the basis of which FDA may identify the “later” event as	617
described in section 505(j)(5)(D)(i)(I) of the FD&C Act. The provision does not effect a	618
forfeiture when an event under item (aa) has occurred, but no event under item (bb) has yet	619
occurred.	620
621
Q26. 	Does an NDA holder’s request to remove the qualifying patent from the Orange	622
Book qualify as a triggering event under subitem (bb)(CC)?	623
624
No. An NDA holder’s request that the qualifying patent be removed from the Orange Book does	625
not constitute an event under subitem (CC) because as described in Question 13, FDA will not	626
remove a patent from the Orange Book if the removal would deprive a first applicant of 180-day	627
exclusivity to which it is otherwise entitled. This policy prevents an NDA holder from removing	628
a qualifying patent in order to deprive a first applicant of the period of 180-day exclusivity for	629
which it is otherwise eligible.54
630
631
2. 	Withdrawal of Application Forfeiture Provision	632
633
A forfeiture event occurs under this provision if “[t]he first applicant withdraws the application	634
or [FDA] considers the application to have been withdrawn as a result of [FDA’s] determination	635
. . . that the application does not meet the requirements for approval under [section 505(j)(4) of	636
the FD&C Act].”55
637
638
Q27. 	How does FDA determine forfeiture under the “withdrawal of application”	639
forfeiture provision?	640
641
The withdrawal of application provision provides for forfeiture under two conditions: (1) if the	642
first applicant withdraws the application or (2) if FDA considers the application withdrawn for	643
failure to meet the various general requirements for approval laid out in section 505(j)(4) of the	644
FD&C Act. A first applicant’s affirmative withdrawal of its ANDA would meet the first	645
condition, resulting in a forfeiture under this provision. FDA has not yet considered a forfeiture	646
under the second condition.	647
648
3. 	Amendment of Certification Forfeiture Provision	649
650
54 See Teva v. Sebelius, 595 F.3d at 1318; see also 21 CFR 314.94(a)(12)(viii)(B).
55 Section 505(j)(5)(D)(i)(II) of the FD&C Act.

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A forfeiture event occurs under this provision if “[t]he first applicant amends or withdraws the	651
certification for all of the patents with respect to which that applicant submitted a certification	652
qualifying the applicant for the 180-day exclusivity period.”56
653
654
Q28. 	How does FDA determine forfeiture under the “amendment of certification”	655
forfeiture provision?	656
657
This subsection provides for forfeiture when a first applicant amends or withdraws the paragraph	658
IV certification for all of the patents or claims of patent(s) for which that applicant submitted a	659
paragraph IV certification qualifying the applicant for the 180-day exclusivity period. For	660
instance, forfeiture under this provision occurs when the ANDA applicant loses related patent	661
litigation and amends its ANDA to include a paragraph III certification to all of the qualifying	662
patents.57 As noted above, FDA regulations require ANDA applicants to amend their patent	663
certification “if, at any time before the date of approval of the ANDA, the applicant learns that	664
the submitted certification or statement is no longer accurate.”58 FDA recommends that	665
applicants provide this information to the Agency expeditiously to avoid unnecessary	666
expenditure of resources in considering forfeiture on other grounds.	667
668
Notably, this forfeiture provision does not require a first applicant to have amended or	669
withdrawn all paragraph IV certifications contained in its ANDA to forfeit, just those that	670
qualified the applicant as a first applicant. Accordingly, a first applicant may forfeit its	671
eligibility for exclusivity under this provision, but still maintain paragraph IV certifications to	672
non-qualifying patents. For example, an ANDA applicant submits a substantially complete	673
ANDA with a paragraph IV certification to patent 1 (the only patent listed at that time) and later	674
amends its ANDA to contain a paragraph IV certification to patent 2, which was newly issued by	675
the U.S. Patent and Trademark Office and timely submitted for listing in the Orange Book. If the	676
ANDA applicant withdraws its paragraph IV certification to patent 1, it will forfeit its eligibility	677
for 180-day exclusivity even though the applicant maintains its paragraph IV certification to	678
patent 2. If, on the other hand, the ANDA applicant withdraws its paragraph IV certification to	679
patent 2, but maintains its paragraph IV certification to patent 1, eligibility for 180-day	680
exclusivity will not be affected. This is because only patent 1 qualified the ANDA applicant for	681
180-day exclusivity.	682
683
Q29. 	Does a first applicant forfeit exclusivity under the “amendment of certification”	684
provision when, because of a change in formulation of the proposed generic drug, a first	685
applicant is required to resubmit paragraph IV certifications to the qualifying patents?	686
687
No. Resubmission of paragraph IV certifications in connection with an ANDA applicant’s	688
reformulation of its proposed drug product does not constitute an amendment or withdrawal of	689
the paragraph IV certifications under this forfeiture provision. FDA requires submission of an	690
appropriate patent certification or, for a previously submitted paragraph IV certification, a	691
recertification, in certain circumstances. For example, an appropriate patent certification or	692
56 Section 505(j)(5)(D)(i)(III) of the FD&C Act.
57 See 21 CFR 314.94(a)(12)(viii)(A).
58 21 CFR 314.94(a)(12)(viii)(C)(1)(i).

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statement or a recertification is required, among other bases, when an applicant amends its	693
ANDA to make other than minor changes in product formulation.59 This practice provides	694
notice of the proposed change in formulation of the ANDA product to the NDA holder and each	695
patent owner so that any patent issues related to the new formulation can be resolved. Under	696
applicable regulations, recertification does not constitute an amendment or withdrawal of the	697
paragraph IV certification resulting in forfeiture of 180-day exclusivity. Rather, an ANDA	698
applicant’s resubmission of paragraph IV certifications in connection with reformulation is	699
understood to fulfill the statutory requirement to continuously maintain previous paragraph IV	700
certifications to those patents.60 As explained in the final rule on Abbreviated New Drug	701
Applications and 505(b)(2) Applications, a “subsequent paragraph IV certification to the	702
qualifying patent or patent claim is not an ‘amendment’ of the previously submitted paragraph	703
IV certification under section 505(j)(5)(D)(i)(III) of the FD&C Act because the type of	704
certification remains the same; rather, it is a reaffirmation of the patent challenge	705
notwithstanding the amendment to the ANDA.”61
706
707
Q30. 	Does a license agreement between the first applicant and the NDA holder or patent	708
owner constitute an “amendment of certification” under this provision?	709
710
No. FDA’s regulations provide that a paragraph IV certification remains appropriate if the basis	711
for non-infringement (of an otherwise valid and infringed patent) is that the ANDA applicant has	712
obtained a license from the patent owner with respect to the patent.62
713
714
Nor does an ANDA applicant’s agreement that the qualifying patent is valid and would be	715
infringed in the course of securing a license require the applicant to change the paragraph IV	716
certification to a paragraph III certification, because requiring such a certification change would	717
render the license null. The effect of a paragraph III certification is that the ANDA cannot be	718
approved until the patent expires. If required to change its paragraph IV certification to a	719
paragraph III certification, the ANDA applicant licensee could not have an approved generic	720
drug product to market during the period in which it needed and obtained a license to do so.	721
722
4. 	Failure to Obtain Tentative Approval Forfeiture Provision	723
724
A forfeiture event occurs under this provision if “[t]he first applicant fails to obtain tentative	725
approval of the application within 30 months after the date on which the application is filed,	726
unless the failure is caused by a change in or a review of the requirements for approval of the	727
application imposed after the date on which the application is filed.”63
728
729
Q31. 	How are the dates of the 30-month forfeiture period determined?	730
731
59 21 CFR 314.96(d). See 81 FR 69580, 69615 (Oct. 6, 2016).
60 See 81 FR 69580, 69617-69618 (Oct. 6, 2016).
61 Id.
62 21 CFR 314.94(a)(12)(v).
63 Section 505(j)(5)(D)(i)(IV) of the FD&C Act.

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The starting date of the 30-month period64 in which a first applicant must obtain tentative or final	732
approval or risk forfeiture is one day after the date that a first applicant submits its substantially	733
complete application.65 The last day of the 30-month period lands on the 30-month anniversary	734
date of ANDA submission. For example, for an ANDA filed on February 10, 2005, the 30-	735
month period began on February 11, 2005, and the last day of the 30-month period was August	736
10, 2007.66
737
738
We note that the day after the date of a first applicant’s ANDA submission is the date used to	739
determine the start of the 30-month forfeiture period even if the ANDA originally did not contain	740
a paragraph IV certification, but was amended later to contain one that qualified the applicant as	741
a first applicant. Thus, it is possible that FDA could determine that an applicant forfeited its	742
eligibility for exclusivity under this provision based on the 30-month period beginning before	743
submission of a paragraph IV certification.	744
745
The Food and Drug Administration Safety and Innovation Act67 (FDASIA) created an exception	746
to this general rule regarding the 30-month forfeiture period and paragraph IV certifications	747
submitted in an amendment. The law provides that for applications submitted on or before July	748
9, 2012, and amended to first contain a paragraph IV certification between July 10, 2012, and	749
September 30, 2017, the 30-month forfeiture period begins the day after the date of submission	750
of the paragraph IV amendment, rather than the day after the date of submission of the	751
substantially complete ANDA.68
752
753
Q32. 	Is the 30-month forfeiture period ever extended or modified?	754
755
Yes. First, subsection 505(q)(1)(G) of the FD&C Act, enacted as part of the Food and Drug	756
Administration Amendments Act of 2007,69 concerns the submission of citizen petitions that	757
relate to already pending ANDAs and provides that “[i]f the filing of an application resulted in	758
first-applicant status under subsection (j)(5)(D)(i)(IV) and approval of the application was	759
delayed because of a petition, the 30-month period under such subsection is deemed to be	760
extended by a period of time equal to the period beginning on the date on which [FDA] received	761
the petition and ending on the date of final agency action on the petition (inclusive of such	762
beginning and ending dates), without regard to whether [FDA] grants, in whole or in part, or	763
denies, in whole or in part, the petition.” Thus, pursuant to this provision, if approval of a first	764
applicant’s ANDA was delayed because of a petition submitted under section 505(q) of the	765
64 We note that this 30-month period in which a first applicant must obtain tentative or final approval is separate
from and calculated differently than the 30-month stay period provided for in section 505(j)(5)(B)(iii) of the FD&C
Act.
65 Section 505(j)(5)(D)(i)(IV) of the FD&C Act. We interpret “the date on which the application is filed” as used in
section 505(j)(5)(D)(i)(IV) of the FD&C Act to refer to the date that a substantially complete ANDA is submitted to
FDA.
66 For certain ANDAs, the Food and Drug Administration Safety and Innovation Act (FDASIA), enacted on July 9,
2012 (Public Law 112-144) directs that this period be extended to 36 or 40 months, as described in Question 32.
67 Pub. Law 112-144.
68 See Section 1133(b) of FDASIA.
69 Pub. Law 110-85.

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FD&C Act70 such that the time it took FDA to respond to the 505(q) petition prevented approval	766
within 30 months from the date of submission, the 30-month deadline for obtaining a tentative or	767
final approval will be extended by the amount of time the 505(q) petition was under review.	768
769
Second, section 1133(a) of FDASIA extended the 30-month period for certain ANDAs. Under	770
FDA’s interpretation of these provisions, for applications submitted between January 9, 2010,	771
and July 9, 2012, containing a paragraph IV certification (or amended to first contain a paragraph	772
IV certification during that period of time), and approved or tentatively approved during the	773
period of time beginning on July 9, 2012, and ending on September 30, 2015, section 1133(a) of	774
FDASIA extended this period to 40 months. For applications submitted between January 9,	775
2010, and July 9, 2012 (or amended to first contain a paragraph IV certification during that	776
period of time), and approved or tentatively approved during the period of time beginning on	777
October 1, 2015, and ending on September 30, 2016, section 1133(a) of FDASIA extended this	778
period to 36 months. In addition, if an application was submitted between January 9, 2010, and	779
July 9, 2012 containing a paragraph IV certification (or amended to first contain a paragraph IV	780
certification during that period of time), and FDA had not approved or tentatively approved the	781
application but must consider whether the applicant had forfeited exclusivity because a	782
potentially blocked application is ready for approval, FDA applied the 36-month period if it	783
made the forfeiture determination between the period of time beginning on October 1, 2015, and	784
ending on September 30, 2016. For all other applications, the 30-month period set forth in	785
section 505(j)(5)(D)(i)(IV) of the FD&C Act applies.	786
787
Q33. 	Does the “failure to obtain tentative approval” forfeiture provision apply to	788
circumstances in which the first applicant was not eligible for tentative approval but failed	789
to obtain final approval by the 30-month forfeiture date?	790
791
Yes. Unless the 30-month period is extended for one of the reasons described above,71 a first	792
applicant that fails to obtain either tentative approval or final approval of its ANDA by the 30-	793
month forfeiture date generally will forfeit eligibility for 180-day exclusivity. Viewed in	794
isolation, the phrase tentative approval in section 505(j)(5)(D)(i)(IV) of the FD&C Act might	795
suggest that this section applies only when an ANDA is eligible for a tentative approval due to a	796
patent, 30-month stay, or exclusivity blocking final approval. Such a reading of the statute	797
would result in incongruous circumstances in which first applicants that are eligible for tentative	798
approval can forfeit under this provision, but first applicants that only are eligible for final	799
approval (and arguably closer to marketing) cannot forfeit under this provision. Other references	800
to this forfeiture provision in the statute make clear that the provision has a broader scope. For	801
example, section 505(q)(1)(G) of the FD&C Act expressly states that if “approval” of the first	802
applicant’s application was delayed because of a petition, the 30-month period described in	803
section 505(j)(5)(D)(i)(IV) of the FD&C Act will be extended. In light of this language, FDA	804
has concluded that section 505(j)(5)(D)(i)(IV) establishes a 30-month period within which a first	805
applicant generally must obtain either tentative approval or final approval of its ANDA. This	806
interpretation squares both with the statutory language and with the statutory purpose of	807
70 In general, section 505(q) of the FD&C Act pertains, in relevant part, to petitions that request an action that could
delay approval of a pending ANDA or 505(b)(2) application.
71 See Question 32.

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preventing first applicants’ ANDAs that do not meet the substantive requirements for approval	808
from delaying approval of subsequent applicants’ ANDAs.	809
810
Q34. 	How does a first applicant qualify for the exception in the “failure to obtain	811
tentative approval” forfeiture provision?	812
813
To qualify for the exception to this forfeiture provision, the failure to obtain tentative or final	814
approval must be “caused by a change in or a review of the requirements for approval of the	815
application imposed after the date on which the application is filed.”72 In other words, two	816
conditions must both be met: (1) FDA changed or reviewed (i.e., considered whether to change)	817
the requirements for approval while the application was under review and (2) this change in, or	818
review of, approval requirements was a cause of the failure to obtain tentative approval or final	819
approval by the 30-month forfeiture date. However, FDA has determined that “but-for”	820
causation is not required to qualify for this exception. In other words, if one of the causes of	821
failure to obtain tentative or final approval by the 30-month forfeiture date was a change in or	822
review of the requirements for approval imposed after the application was filed, an applicant will	823
not forfeit eligibility for exclusivity notwithstanding that there may have been other causes for	824
failure to obtain tentative approval or final approval by the 30-month forfeiture date.	825
Consequently, to qualify for the exception, the record must show that acceptability of at least one	826
aspect of the ANDA (e.g., bioequivalence) was delayed and, irrespective of what other review	827
issues may have been outstanding at the 30-month date, that this delay was caused, at least in	828
part, by a change in, or review of, the requirements for approval. FDA has determined that this	829
interpretation of the statute best effectuates the policy underlying the exception. It does not	830
penalize applicants for FDA’s reviews of, or changes in, approval requirements imposed on	831
applicants after their ANDAs are filed that are a cause of the failure to obtain final approval or	832
tentative approval within 30 months. This interpretation also continues to incentivize ANDA	833
applicants to challenge patents by preserving in many instances the opportunity to obtain 180-	834
day exclusivity.	835
836
Q35. 	Can a first applicant qualify for the exception if, at the 30-month forfeiture date,	837
FDA is reviewing an ANDA amendment submitted to address a change in the requirements	838
for approval?	839
840
Yes. FDA generally will presume that failure to obtain tentative approval or final approval was	841
caused by a change in, or review of, approval requirements if, at the 30 month date, the evidence	842
demonstrates that there was a change in, or review of, the requirements for approval and that the	843
applicant was actively addressing issues related to the change in, or review of, approval	844
requirements (or FDA was considering such efforts), and these efforts precluded tentative	845
approval or final approval at that time. When the evidence fails to demonstrate that the applicant	846
was actively addressing the change in, or review of, approval requirements, and that these	847
activities precluded tentative approval or final approval at the 30-month date, FDA generally	848
does not presume that the failure was caused by a change in, or review of, approval	849
requirements. If FDA were to hold otherwise, an applicant that receives one or more	850
deficiencies resulting from a change in approval requirements could avoid forfeiture by a delay	851
72 Section 505(j)(5)(D)(i)(IV) of the FD&C Act.

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in addressing those deficiencies. When evaluating causation for purposes of determining	852
forfeiture under this provision, FDA will take into account how close the change in or review of	853
the requirement for approval occurred to the 30-month date as well as the amount of effort	854
needed to respond to the change. Further, if the applicant’s response is submitted after the 30-	855
month date, FDA will consider, among other factors, how close the response is submitted to the	856
30-month date.	857
858
Q36. 	Does the exception to the “failure to obtain tentative approval” forfeiture provision	859
apply if FDA’s review of an ANDA takes longer than 30 months in the absence of a change	860
in or review of the approval requirements?	861
862
No. Under this forfeiture provision, exclusivity is forfeited “unless” there is a review of or	863
change in the approval requirements that has delayed final approval or tentative approval of the	864
ANDA. The statute does not permit FDA to consider an exception based on whether the	865
application could have received tentative approval or final approval before the 30-month	866
forfeiture date had FDA’s review been conducted differently. Section 1133 of FDASIA	867
(referenced in Question 32), which, among other things, extended the 30-month forfeiture period	868
to 40 months for certain ANDAs and to 36 months for certain other ANDAs, reflects Congress’s	869
understanding that, even in the absence of a change in or review of the requirements for	870
approval, FDA’s review of an ANDA might take more than 30 months and might contribute to a	871
first applicant’s failure to obtain tentative approval or final approval by the 30-month forfeiture	872
date and result in forfeiture of exclusivity.	873
874
Q37. 	What are examples of changes in the requirements for approval that formed the	875
basis of an exception to the “failure to obtain tentative approval” forfeiture provision?	876
877
The following are examples of changes in the requirements for approval imposed after ANDA	878
submission that FDA has determined were a cause of failure to obtain tentative or final approval	879
in 30 months and therefore formed the basis of an exception to this forfeiture provision:	880
881
• 	FDA’s change in approval requirements related to drug quality that required an applicant	882
to conduct additional testing and include an additional new drug substance specification;	883
• 	FDA’s change in approval requirements for demonstrating bioequivalence for a drug	884
product;	885
• 	Changes in the RLD labeling that required changes in the ANDA applicant’s generic	886
drug labeling;	887
• 	Changes in an RLD’s formulation that required an ANDA applicant to respond (for	888
example, by seeking approval for a change in formulation); and	889
• 	The publication in the United States Pharmacopeia-National Formulary of a final	890
monograph for a drug product making it necessary for applicants to demonstrate	891
compliance with the new compendial standards.73
892
73 This list is intended to be illustrative and not exhaustive.

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893
Q38. 	Can FDA’s review of an approval requirement result in an exception to the “failure	894
to obtain tentative approval” forfeiture provision even if the approval requirements	895
ultimately do not change?	896
897
Yes. FDA’s review, without change, of approval requirements can be a cause of failure to obtain	898
tentative or final approval within 30 months.	899
900
For example, assume FDA originally determines a particular bioequivalence method to be	901
acceptable for a tablet dosage form. Sometime before the 30-month forfeiture date, FDA	902
identifies concerns related to certain dissolution data for one or more tablet products and decides	903
to ask pending ANDAs to develop and propose a different dissolution method, which the	904
applicants provide. After the 30-month forfeiture date, FDA asks a first applicant that had	905
proposed a modified dissolution method to repeat its dissolution testing for all strengths of the	906
company’s drug product using the new method. The first applicant submits an amendment with	907
the dissolution data derived from the modified method. FDA ultimately determines after the	908
forfeiture date that FDA’s originally recommended dissolution method was appropriate.	909
Because FDA’s review of the bioequivalence requirements was a cause of the failure to obtain	910
timely tentative or final approval, the exception to the failure to obtain tentative approval	911
forfeiture provision would still apply even though FDA ultimately did not change the dissolution	912
methods.	913
914
Q39. 	Can FDA’s consideration of issues raised in a citizen petition related to the	915
requirements for ANDA approval provide the basis of an exception to the forfeiture	916
provision if an ANDA is submitted after the petition is submitted and is reviewed while that	917
petition is pending?	918
919
Yes, assuming the other criteria for the exception are met. Specifically, if the review of issues	920
raised in a petition submitted before submission of the first applicant’s ANDA continues after	921
ANDA submission and during ANDA review, FDA’s consideration of the issues raised in the	922
petition can constitute a change in or review of requirements for approval.	923
924
5. 	Agreement with Another ANDA Applicant, the Listed Drug Application Holder, or a	925
Patent Owner	926
927
A forfeiture event occurs under this provision if “[t]he first applicant enters into an agreement	928
with another applicant […] for the drug, the holder of the application for the listed drug, or an	929
owner of the patent that is the subject of [a paragraph IV] certification […], the Federal Trade	930
Commission or the Attorney General files a complaint, and there is a final decision of the	931
Federal Trade Commission or the court with regard to the complaint from which no appeal (other	932
than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the	933
agreement has violated the antitrust laws […].”74
934
935
74 Section 505(j)(5)(D)(i)(V) of the FD&C Act.

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Q40. 	Are there examples of forfeiture under the provision related to agreements with	936
another applicant, the NDA holder, or a patent owner?	937
938
No. As of the date of publication of this draft guidance, FDA has not determined that a first	939
applicant has forfeited its eligibility for exclusivity under this provision, sometimes referred to as	940
the collusive agreement forfeiture provision. We note that the collusive agreement forfeiture	941
provision applies to all pending ANDAs, regardless of when the first ANDA referencing the	942
RLD was submitted.75 This is not the case for the other forfeiture provisions.76 We also note	943
that the collusive agreement forfeiture provision applies to only those settlement agreements	944
described in the statute when, among other things, there is a final decision of the Federal Trade	945
Commission or court that the agreement has violated the antitrust laws, and the decision cannot	946
be or has not been appealed.	947
948
6. 	Expiration of All Patents Forfeiture Provision	949
950
A forfeiture event occurs under this provision if “[a]ll of the patents as to which the applicant	951
submitted a certification qualifying it for the 180-day exclusivity period have expired.”77
952
953
Q41. 	Does forfeiture under the “expiration of all patents” provision require the	954
expiration of all listed patents to which a first applicant submitted a paragraph IV	955
certification?	956
957
No. A forfeiture under this provision occurs upon expiration of only all of the qualifying	958
patent(s). Forfeiture can occur under this provision even if the first applicant has paragraph IV	959
certifications to other listed patents that have not expired as long as the certification to these	960
other patents did not provide the basis for eligibility for 180-day exclusivity. For example,	961
suppose an ANDA applicant is the first applicant based on the submission of a substantially	962
complete ANDA containing a paragraph IV certification to U.S. Patent No. 3,456,879 (the ‘879	963
patent). After submission of the ANDA, U.S. Patent No. 6,789,101 (the ‘101 patent) for the	964
RLD is listed and the ANDA applicant amends its application to include a paragraph IV	965
certification to it. The ANDA applicant will forfeit exclusivity upon expiration of the ‘879	966
patent (the only qualifying patent), even if the ‘101 patent remains unexpired.	967
968
7. 	Effect of Forfeiture	969
970
75 Section 1102(b)(2) of the MMA.
76 See Question 1. Section 1102(b)(1) of the MMA provides that, except as provided in section 1102(b)(2), the
provisions related to 180-day exclusivity “shall be effective only with respect to an application filed under [section
505(j) of the FD&C Act] after the date of the enactment of this Act for a listed drug for which no certification under
section 505(j)(2)(A)(vii)(IV) of that Act was made before the date of the enactment of this Act.” Section 1102(b)(2)
in turn provides that “[i]f a forfeiture event described in section 505(j)(5)(D)(i)(V) of [the FD&C Act] occurs in the
case of an applicant, the applicant shall forfeit the 180-day period under section 505(j)(5)(B)(iv) of [the FD&C Act]
without regard to when the first certification under section 505(j)(2)(A)(vii)(IV) of [the FD&C Act] for the listed
drug was made.”
77 Section 505(j)(5)(D)(i)(VI) of the FD&C Act.

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Q42. 	Does a first applicant that forfeited its eligibility for exclusivity become a	971
“subsequent applicant” blocked from final approval by other first applicants’ eligibility for	972
exclusivity?	973
974
No. The FD&C Act provides that “[t]he 180-day exclusivity period […] shall be forfeited by a	975
first applicant if a forfeiture event occurs with respect to that first applicant.”78 Neither this	976
statutory provision, nor any other, states that in forfeiting exclusivity, a first applicant becomes a	977
subsequent applicant whose ANDA can be approved only after the 180-day exclusivity period	978
has run. Thus, FDA interprets the statute such that a first applicant that has forfeited exclusivity	979
remains a first applicant and need not await expiration of 180-day exclusivity to obtain approval	980
of its ANDA. A first applicant that has forfeited exclusivity is subject to the same timetable for	981
approval that governs the approval of ANDAs for first applicants that remain eligible for 180-	982
day exclusivity.79 Section 505(j)(5)(B)(iv) of the FD&C Act, which governs the running of 180-	983
day exclusivity, does not distinguish between first applicants that have forfeited eligibility for	984
180-day exclusivity and those that have not, providing instead only that a subsequent applicant’s	985
ANDA may be approved 180 days after the date of first commercial marketing by any first	986
applicant. In addition, once FDA has approved one or more ANDAs, commercial marketing by	987
any first applicant will trigger the 180-day exclusivity period for all the first applicant ANDAs,	988
even if the triggering applicant is the first applicant that forfeited its eligibility for exclusivity.	989
990
For example, assume ANDA A and ANDA B are first applicants. ANDA A forfeits its	991
eligibility for 180-day exclusivity for failure to obtain tentative approval within 30 months but	992
ANDA B maintains its eligibility. ANDA A is not blocked from approval by ANDA B’s 180-	993
day exclusivity because ANDA A remains a first applicant. ANDA A also can trigger ANDA	994
B’s 180-day exclusivity. However, ANDA A will not itself block subsequent applicants from	995
approval. Only ANDA B, which retained eligibility for exclusivity, will block subsequent	996
applicants from approval.	997
998
Q43. 	If 180-day exclusivity is forfeited by the first applicant(s), does it “roll” to the next-	999
submitted ANDA?	1000
1001
No. 180-day exclusivity is only available to those ANDA applicants that meet the statutory	1002
definition of first applicant.80 Thus, any subsequent applicant that did not submit a substantially	1003
complete ANDA that contained a paragraph IV certification on the first day such an application	1004
was submitted does not qualify for exclusivity. Once 180-day exclusivity is forfeited by all the	1005
first applicants, it no longer blocks approval of any subsequent applicants’ ANDAs but	1006
subsequent applicants do not become first applicants under those circumstances.	1007
1008
1009
G. 	Procedural Questions Regarding 180-day Exclusivity Determinations	1010
1011
78 Section 505(j)(5)(D)(ii) of the FD&C Act.
79 Section 505(j)(5)(B)(iii) of the FD&C Act.
80 Section 505(j)(5)(B)(iv)(II)(bb) of the FD&C Act.

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Q44. 	When does FDA decide whether an ANDA applicant is eligible for 180-day	1012
exclusivity?	1013
1014
It is FDA’s practice to make decisions on eligibility for 180-day exclusivity in the context of	1015
specific ANDAs that are otherwise eligible for approval (i.e., when a first applicant’s ANDA or a	1016
subsequent applicant’s ANDA is ready for approval). Many factors may influence eligibility for	1017
exclusivity up to the time an application is ready for approval (e.g., patent expiration, failure to	1018
obtain a tentative or final approval within 30 months, withdrawal of ANDA) and thus could	1019
render a premature eligibility determination incorrect. When FDA makes an approval decision	1020
with respect to an ANDA, it will inform an applicant affected by exclusivity of its status. For	1021
example, FDA generally will inform an ANDA applicant it is (1) a first applicant entitled to	1022
exclusivity, (2) a first applicant that has forfeited its exclusivity, (3) eligible only for a tentative	1023
approval because one or more first applicants are eligible for 180-day exclusivity, or (4) eligible	1024
for final approval because all first applicants have forfeited exclusivity.	1025
1026
In some circumstances, when a first applicant is ready for final approval, FDA may refrain from	1027
making a formal determination regarding that applicant’s eligibility for 180-day exclusivity.	1028
Specifically, if FDA’s review of the ANDAs for the drug product indicates that a formal	1029
determination of eligibility for 180-day exclusivity is not necessary (e.g., if there are no	1030
subsequent ANDAs or the subsequent ANDAs are likely more than 180 days away from final	1031
approval), FDA may refrain from making a formal determination regarding eligibility for 180-	1032
day exclusivity.	1033
1034
It also is possible that an ANDA applicant could be informed upon approval that it is a first	1035
applicant eligible for 180-day exclusivity, but later forfeit exclusivity under section 505(j)(5)(D)	1036
of the FD&C Act.	1037
1038
Q45. 	How can the public know if a paragraph IV certification has been submitted with	1039
respect to a particular RLD?	1040
1041
FDA maintains on its website a list of drug products for which an ANDA has been received by	1042
the Agency containing a paragraph IV certification. The webpage is titled Paragraph IV Patent	1043
Certifications.81 This list includes the drug product for which a paragraph IV certification has	1044
been submitted, the dosage form, strength(s), RLD name, and date on which the first	1045
substantially complete ANDA was submitted to FDA or, when applicable, the date of the first	1046
paragraph IV certification. FDA will not disclose the identity of the applicants of those ANDAs,	1047
nor will FDA indicate the number of such ANDAs submitted on that date. The information is	1048
updated twice a month and is as current as the last update. Although FDA makes every effort to	1049
ensure the accuracy of the information provided in this list, this information should be used for	1050
reference only. Any discrepancies, disparities, or other questions about this information should	1051
be discussed with the Office of Generic Drug’s Division of Filing Review before making any	1052
decisions based on the information.	1053
81 This FDA webpage is available at
http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/a
bbreviatednewdrugapplicationandagenerics/ucm047676.htm.