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DRAFT GUIDANCE
 
 
This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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Draft  Not for Implementation 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 PATHWAY ............................................................................................. 2 
B.  PATENT CERTIFICATION AND 180-DAY EXCLUSIVITY.............................................3 
III.  QUESTIONS AND ANSWERS ........................................................................................... 5 
A.  APPLICABLE STATUTORY SCHEME...................................................................5 
B.  FIRST APPLICANTS ............................................................................................................... 6 
C.  180-DAY EXCLUSIVITY AND PATENTS ............................................................................... 10 
D.  180-DAY EXCLUSIVITY TRIGGER AND SCOPE OF 180-DAY EXCLUSIVITY .......................... 11 
E.  180-DAY EXCLUSIVITY RELINQUISHMENT AND WAIVER ................................................... 14 
F.  FORFEITURE OF 180-DAY EXCLUSIVITY ............................................................................. 14 
G.  PROCEDURAL QUESTIONS REGARDING 180-DAY EXCLUSIVITY DETERMINATIONS ........... 26 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Guidance for Industry 
1
2  180-Day Exclusivity: Questions and Answers  
3   
4   
5  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
6  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
7  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
8  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
9  for this guidance as listed on the title page.   
10   
11   
12   
13   
14  I.  INTRODUCTION  
15   
16  This guidance is intended to address questions that have been raised about the provisions of the 
17  Federal Food, Drug, and Cosmetic Act (FD&C Act) that relate to generic drug exclusivity, which 
18  commonly is known as 180-day exclusivity for generic drug products.  As a general matter, the 
19  Food and Drug Administration (FDA or the Agency) has implemented these statutory provisions 
20  within the context of application-specific decisions.  Some FDA decisions have been made 
21  publicly available (e.g., in FDA citizen petition responses and documents released in litigation).  
22  In addition, in certain circumstances where a novel issue of interpretation was raised by a 
23  particular factual scenario regarding forfeiture of 180-day exclusivity, FDA has opened a public 
24  docket or otherwise sought comment from affected parties in advance of taking an action.  Also, 
25  in certain instances, applicants have submitted correspondence to their abbreviated new drug 
26  applications (ANDAs) regarding 180-day exclusivity, which FDA has considered in making 
27  decisions.  FDA believes that a guidance for industry that provides answers to commonly asked 
28  questions about 180-day exclusivity would enhance transparency and facilitate the development, 
29  approval, and timely marketing of generic drug products.  FDA intends to update this guidance 
30  to include additional questions and answers (Q&As) as appropriate. 
31   
32  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
33  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
34  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
35  the word should in Agency guidances means that something is suggested or recommended, but 
36  not required.  
37   
38  II.  BACKGROUND 
39   
40  The Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman 
41  Amendments)2 to the FD&C Act established the ANDA approval pathway for generic drugs.3  In 
                                                 
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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Draft  Not for Implementation 
42  2003, Congress enacted the Medicare Prescription Drug, Improvement, and Modernization Act 
43  of 2003 (MMA),4 which, among other things, substantially revised certain statutory provisions 
44  related to 180-day exclusivity.  In this guidance, we will discuss 180-day exclusivity as it 
45  pertains to ANDAs subject to the MMA statutory provisions.  This guidance does not discuss 
46  180-day exclusivity as it pertains to ANDAs subject to the pre-MMA statutory provisions.  In 
47  Section III.A, we describe how to determine which statutory scheme applies to a particular 
48  ANDA. 
49   
50  A.  ANDA Approval Pathway 
51   
52  The process for obtaining approval to market an innovator drug approved under a new drug 
53  application (NDA) differs from that for obtaining approval to market a generic drug under an 
54  ANDA.  A sponsor of an innovator drug must submit an NDA, which must contain, among other 
55  things, a demonstration of the safety and effectiveness of the drug for the conditions of use for 
56  which approval is sought.5  In its application, an NDA applicant must submit information for 
57  each patent that claims the drug or method of using the drug and for which a claim of patent 
58  infringement could reasonably be asserted against a person engaged in the unlicensed 
59  manufacture, use, or sale of the drug product.6  Upon approval of an NDA, FDA publishes this 
60  patent information in its publication Approved Drug Products with Therapeutic Equivalence 
61  Evaluations, known as the Orange Book.7 
62   
63  To obtain approval of a generic drug, an ANDA applicant is not required to provide independent 
64  evidence of the safety and effectiveness of the proposed generic drug.  Instead, the applicant 
65  relies on FDAs previous finding that the reference listed drug (RLD)8 relied upon by the ANDA 
66  applicant is safe and effective.  The ANDA applicant must identify the RLD on which it seeks to 
67  rely and, among other things, demonstrate, with limited exceptions, that the proposed generic 
68  drug has the same active ingredient(s), route of administration, dosage form, and strength as the 
69  RLD.9  A generic drug also must have the same conditions of use and the same labeling as the 
70  RLD (except for certain permissible labeling differences),10 and the applicant must demonstrate 
71  that its proposed generic drug is bioequivalent to the RLD.11  
                                                                                                                                                             
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). 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
72   
73  B.  Patent Certification and 180-day Exclusivity 
74   
75  The timing of ANDA approval depends on, among other things, the patent and exclusivity 
76  protections for the RLD.  An applicant must provide in its ANDA additional information related 
77  to any patents for the RLD.  In particular, the ANDA applicant generally must submit to FDA 
78  one of four specified certifications regarding the patents for the RLD under section 
79  505(j)(2)(A)(vii) of the FD&C Act.   
80   
81  If the Orange Book does not list a patent for the RLD, the ANDA applicant must certify: 
82   
83  1.  That such patent information has not been submitted by the NDA holder for listing in the 
84  Orange Book (a paragraph I certification).12 
85   
86  With respect to each patent listed in the Orange Book for the RLD, the applicants patent 
87  certification must state one of the following: 
88   
89  2.  That such patent has expired (a paragraph II certification) 
90  3.  The date on which such patent will expire (a paragraph III certification) 
91  4.  That such patent is invalid, unenforceable, or will not be infringed by the manufacture, 
92  use, or sale of the new drug for which the application is submitted (a paragraph IV 
93  certification).13 
94   
95  If an applicant submits a paragraph I or II certification, the patent in question will not delay 
96  ANDA approval.  If an applicant submits a paragraph III certification, the applicant agrees to 
97  wait until the relevant patent has expired before seeking final approval of its ANDA.  If, 
98  however, an applicant wishes to seek approval of its ANDA before a listed patent has expired by 
99  challenging the validity of a patent, claiming that a patent would not be infringed by the product 
100  proposed in the ANDA, or claiming a patent is unenforceable, the applicant must submit a 
101  paragraph IV certification to FDA.  
102   
103  The FD&C Act describes only one circumstance in which an ANDA applicant need not certify to 
104  a listed patent.  Specifically, when a patent is listed only for a method of use, an ANDA 
105  applicant seeking to omit that approved method of use from the generic drugs labeling can 
106  submit a section viii statement, acknowledging that a given method-of-use patent has been listed, 
107  but stating that the patent at issue does not claim a use for which the applicant seeks approval.14 
108   
109  An applicant submitting a paragraph IV certification to a listed patent must provide the NDA 
110  holder and each patent owner notice of its paragraph IV certification, including a description of 
111  the legal and factual basis for the ANDA applicants assertion that the patent is invalid, 
                                                 
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). 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
112  unenforceable, or will not be infringed.15  If a patent is listed at the time an ANDA is submitted 
113  and, in response to notice of a paragraph IV certification, the NDA holder or patent owner 
114  initiates a patent infringement action against the ANDA applicant within 45 days of receiving the 
115  required notice, approval of the ANDA generally will be stayed for 30 months from the later of 
116  the date of receipt of the notice by any owner of the patent or the NDA holder or such shorter or 
117  longer time as the court might order.16  If a patent is listed in the Orange Book after an ANDA is 
118  submitted but before it is approved, the applicant for the pending ANDA generally must amend 
119  its application and provide an appropriate patent certification or statement to the newly listed 
120  patent; however, no 30-month stay will be available in this circumstance.17 
121   
122  The statute provides an incentive and a reward to generic drug applicants that expose themselves 
123  to the risk of patent litigation.  It does so by granting a 180-day period of exclusivity vis-a-vis 
124  certain other ANDA applicants to the applicant that is first to file a substantially complete 
125  ANDA containing a paragraph IV certification to a listed patent.  If only one such ANDA is filed 
126  on the first day, there is only one first applicant; if two or more such ANDAs are filed on the 
127  first day, the ANDA applicants share first-applicant status.18  If an ANDA contains a paragraph 
128  IV certification for a relevant patent and the ANDA is not that of a first applicant, the ANDA 
129  applicant is regarded as a subsequent applicant.19   
130   
131  If an ANDA meets the substantive requirements for approval, but cannot be finally approved due 
132  to unexpired patents or exclusivities, FDA will tentatively approve the ANDA.  Tentative 
133  approval means notification to an applicant by [FDA] that an [ANDA] meets the requirements 
134  of [section 505(j)(2)(A) of the FD&C Act] but cannot receive effective approval because the 
135  application does not meet the requirements of this subparagraph, there is a period of exclusivity 
136  for the listed drug under subparagraph (F) or section 505A, or there is a 7-year period of 
137  exclusivity for the listed drug under section 527.20   
138   
139  The FD&C Act describes a number of conditions under which an ANDA applicant may forfeit 
140  eligibility for 180-day exclusivity.  These forfeiture events can be generally described as: (1) 
141  failure to market; (2) withdrawal of application; (3) amendment of certification; (4) failure to 
142  obtain tentative approval; (5) entry into agreement with another applicant, the listed drug 
                                                 
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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Draft  Not for Implementation 
143  application holder, or a patent owner; and (6) expiration of all patents.21  Under these provisions, 
144  if certain events occur, an applicant eligible for 180-day exclusivity at the time its ANDA was 
145  submitted (first applicant) may forfeit eligibility for 180-day exclusivity.  If all first applicants 
146  forfeit their eligibility for 180-day exclusivity, no applicant will be eligible for 180-day 
147  exclusivity, and FDA may approve subsequent applicants ANDAs, subject to the approval 
148  requirements of the FD&C Act.   
149   
150  FDA has received a number of questions about 180-day exclusivity and has identified the 
151  following commonly asked questions for inclusion in this guidance.  FDA expects the following 
152  information to enhance transparency and facilitate the development, approval, and timely 
153  marketing of generic drugs.  FDA intends to update this guidance to include additional Q&As as 
154  appropriate. 
155   
156  III.  QUESTIONS AND ANSWERS 
157   
158  A.  Applicable Statutory Scheme 
159   
160  Q1.  How does FDA determine whether the pre-MMA or MMA provisions of the FD&C 
161  Act apply to a particular ANDA? 
162   
163  Section 1102(b)(1) of the MMA provides that the MMA 180-day exclusivity provisions are 
164  effective only with respect to an ANDA filed after the date of enactment (i.e., December 8, 2003) 
165  for a listed drug for which no paragraph IV certification was made before that date.22  The 
166  following list illustrates how FDA has applied this effective date provision in particular 
167  situations: 
168   
169    If all ANDAs referencing a particular RLD are submitted to FDA after December 8, 2003 
170  (and thus no paragraph IV certification could have been submitted before December 8, 
171  2003), the MMA 180-day exclusivity provisions apply to all of the ANDAs. 
172    If at least one ANDA with a paragraph IV certification to a listed patent for the RLD was 
173  submitted before December 8, 2003, all ANDAs referencing that RLD (including 
174  ANDAs submitted after December 8, 2003) are governed by the pre-MMA statutory 
175  provisions.  
176    If one or more ANDAs referencing a particular RLD were submitted before December 8, 
177  2003, but the first paragraph IV certification was submitted after December 8, 2003, the 
178  pre-MMA provisions govern for any ANDA referencing that RLD (whether or not that 
179  particular ANDA was filed before or after December 8, 2003), because section 
180  1102(b)(1) of the MMA is based on the date of submission of the first application, not on 
181  the date of the first paragraph IV certification. 
182  FDA has concluded that the effective date provision imposes the same statutory scheme on all 
183  ANDAs referencing a specific RLD.  An attempt by FDA to apply both pre-MMA and MMA 
                                                 
21 Section 505(j)(5)(D) of the FD&C Act. 
22 Section 1102(b)(1) of the MMA. 
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Draft  Not for Implementation 
184  statutory schemes to a single group of applications with a common RLD could result in conflict 
185  between the MMA and pre-MMA provisions.  The eligibility, triggering, and forfeiture features 
186  of the different 180-day exclusivity schemes could render one applicant ineligible for exclusivity 
187  while another applicant could retain its eligibility.  To avoid these inequitable outcomes, all 
188  ANDAs submitted referencing the same RLD will be subject to one statutory scheme. 
189   
190  B.  First Applicants 
191   
192  Q2.  How does an ANDA applicant qualify as a first applicant? 
193   
194  A first applicant is an ANDA applicant that, on the first day on which a substantially complete 
195  application containing a [paragraph IV] certification ... is submitted for approval of a drug, 
196  submits a substantially complete application that contains and lawfully maintains a [paragraph 
197  IV] certification ... for the drug.23 
198   
199  An applicant that previously submitted a substantially complete ANDA that did not contain a 
200  paragraph IV certification may become eligible for 180-day exclusivity by amending its ANDA 
201  to contain a paragraph IV certification to a listed patent for the RLD on the first day that an 
202  ANDA or amendment containing a paragraph IV certification is submitted. 
203   
204  The listed patent or patents to which an ANDA applicant submitted a paragraph IV certification 
205  that gives rise to the eligibility for 180-day exclusivity is referred to in this draft guidance as the 
206  qualifying patent(s). 
207   
208  Q3.  What constitutes a substantially complete application? 
209   
210  A substantially complete application is an ANDA that on its face is sufficiently complete to 
211  permit a substantive review.  Sufficiently complete means that the ANDA contains all the 
212  information required under section 505(j)(2)(A) of the FD&C Act and does not contain a 
213  deficiency described in 21 CFR 314.101(d) and (e).24  FDA indicates its determination that an 
214  ANDA is substantially complete when the Agency receives the ANDA for review under 21 CFR 
215  314.101.  If FDA determines, after an initial evaluation, that an ANDA was substantially 
216  complete as of the date it was submitted to FDA, FDA will consider the ANDA to have been 
217  received as of the date of submission.25 
218     
219  Q4.  Does an ANDA applicant have to be the first to submit a paragraph IV certification 
220  to all of the RLDs listed patents to be a first applicant?   
221   
222  No.  The statute requires a paragraph IV certification;26 it does not require a first applicant to 
223  be the first to submit a paragraph IV certification to more than a single patent (or all of the 
224  patents), even if multiple patents are listed for the RLD.   
                                                 
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   
226  There can be multiple patents that could qualify a single ANDA applicant as a first applicant, so 
227  long as they are certified to on that same first day that the first paragraph IV certification in an 
228  ANDA for that RLD is submitted.  As a result, each qualifying patent separately can affect 
229  exclusivity.  For example, if an ANDA applicant submitted paragraph IV certifications to two 
230  separate patents on the same first day and the first patent expires prior to triggering of 180-day 
231  exclusivity, the paragraph IV certification to the second patent can remain a basis for first-
232  applicant status and for 180-day exclusivity.   
233   
234  Q5.  Can an ANDA applicant qualify as a first applicant when it includes both a 
235  paragraph IV certification and a section viii statement to a single listed patent? 
236   
237  Yes.  FDA has determined that when both drug product or drug substance claims and method-of-
238  use claims are contained within the same patent, an applicant may file a paragraph IV 
239  certification with respect to the drug product or drug substance patent claim(s) and a section viii 
240  statement with respect to the method-of-use claim(s) in the patent.  This type of certification is 
241  commonly referred to as a split certification.  This approach preserves the NDA holders 
242  statutory right to assert its patent rights regarding the drug substance or drug product claims 
243  before ANDA approval while permitting the ANDA applicant to exercise its statutory right to 
244  avoid infringing a method-of-use claim by seeking approval for fewer than all of the approved 
245  conditions of use for the RLD.  Consistent with this principle, the paragraph IV certification in a 
246  split certification can qualify an applicant for first applicant eligibility.  
247   
248  Q6.  Can an ANDA applicant be a first applicant if the applicant includes a paragraph 
249  III certification to a patent that expires after the patent to which a paragraph IV 
250  certification was submitted? 
251   
252  Yes.  The statutory definition of first applicant requires a paragraph IV certification.  The 
253  statute does not require that the paragraph IV certification be to the latest expiring patent.  For 
254  example, a first applicant could have a paragraph IV certification to a patent expiring on January 
255  1, 2020 (the only qualifying patent) and a paragraph III certification to a patent expiring on June 
256  1, 2030.  
257   
258  Q7.  Could the timing of sending notice of paragraph IV certification affect first 
259  applicant status? 
260   
261  Yes.  For original ANDAs, notice of paragraph IV certification must be provided on or after the 
262  date on which the applicant receives a paragraph IV acknowledgment letter from FDA, but not 
263  later than 20 days after the date of the postmark on the paragraph IV acknowledgment letter.27  
264  The paragraph IV acknowledgment letter is a written, postmarked communication from FDA to 
265  an applicant stating that the Agency has determined that an ANDA containing a paragraph IV 
266  certification is sufficiently complete to permit a substantive review and has been received for 
                                                 
27 21 CFR 314.95(b)(1). 
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267  review.28  Any notice sent before the ANDA applicants receipt of a paragraph IV 
268  acknowledgment letter is invalid.29 
269   
270  For amendments containing a paragraph IV certification submitted before the ANDA has been 
271  received for review (i.e., before receipt of a paragraph IV acknowledgment letter), the ANDA 
272  applicant must send notice according to the timeframe described above for original ANDAs.  If 
273  an ANDA applicants notice of its paragraph IV certification is timely provided and the applicant 
274  has not submitted a previous paragraph IV certification, FDA will base its determination of 
275  whether the ANDA applicant is a first applicant on the date of submission of the amendment 
276  containing the paragraph IV certification.30 
277   
278  For amendments submitted after the ANDA has been received for review (i.e., after receipt of an 
279  acknowledgment letter or a paragraph IV acknowledgment letter) and supplements, notice of 
280  paragraph IV certification must be provided at the same time that the amendment or supplement 
281  is submitted to FDA.  If notice is not sent simultaneously with an amendment or supplement, 
282  FDA considers the paragraph IV certification not to be effective until notice is provided.31  For 
283  example, if an ANDA applicant submitted a supplement containing a paragraph IV certification, 
284  but notice of the paragraph IV certification was not provided until 30 days after the submission 
285  of the supplement, FDA would evaluate whether the applicant was a first applicant based on the 
286  date notice was provided, rather than the date of submission of the supplement.  Thus, a delay in 
287  giving notice of certain amendments or supplements could mean a later date for the paragraph IV 
288  certification to become effective which could result in failure to obtain first applicant status (if 
289  another applicant submits a certification that becomes effective in the interim). 
290   
291  Regardless of whether it is an original ANDA, an amendment, or a supplement, a paragraph IV 
292  certification must not be submitted earlier than the first working day after the day the patent is 
293  published in the Orange Book.32   Any notice sent before the first working day after the day the 
294  patent is published in the Orange Book is invalid.33 
295   
296  Q8.  What does it mean to lawfully maintain a paragraph IV certification? 
297   
298  The definition of first applicant requires that the applicant lawfully maintain[] a [paragraph IV] 
299  certification.34  This requires an uninterrupted paragraph IV certification to the qualifying patent 
300  or patent claim.  For example, an applicant has not lawfully maintained its paragraph IV 
301  certification if the applicant initially submits a paragraph IV certification to a patent or patent 
302  claim, and then later amends its ANDA to include a paragraph III certification or a section viii 
303  statement to the qualifying patent or patent claim, and then amends its ANDA again to include a 
304  paragraph IV certification to the same patent or patent claim.  However, if the applicant initially 
305  submits a paragraph IV certification to a qualifying patent or patent claim and subsequently 
                                                 
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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306  submits an amendment that contains a paragraph IV certification to the same qualifying patent or 
307  patent claim (and notice of the paragraph IV certification is sent in accordance with 21 CFR 
308  314.95(d)), the first applicant has lawfully maintained the paragraph IV certification to the patent 
309  or patent claim upon which eligibility for 180-day exclusivity is based.35 
310   
311  In addition, if a district court decides that the qualifying patent has been infringed (and the patent 
312  is valid), and the judgment of the district court is not appealed or is affirmed, the ANDA 
313  applicants paragraph IV certification that the patent was invalid, unenforceable, or not infringed 
314  is no longer accurate.  The applicant would be required to amend its ANDA to change its 
315  paragraph IV certification to a paragraph III certification, which acknowledges the date the 
316  patent expires.36   
317   
318  Q9.  Can there be more than one first applicant for a single drug product? 
319   
320  Yes.  The 180-day exclusivity provisions contemplate that there can be multiple first applicants.37  
321  Multiple ANDAs that include paragraph IV certifications to one or more patents listed for an 
322  RLD often will be submitted to FDA on the day the first such application (or the first paragraph 
323  IV certification) is submitted.  If multiple applicants submit paragraph IV certifications on the 
324  first day that paragraph IV certifications for that RLD are submitted, all will be considered first 
325  applicants.  In addition, different ANDA applicants each can qualify as first applicants by 
326  certifying to different listed patents on the same first day. 
327   
328  Q10.  Do multiple first applicants for a single drug product each get their own 180-day 
329  exclusivity period? 
330   
331  No.  There is one 180-day exclusivity period for each drug product.  Accordingly, whether 
332  multiple first applicants enjoy the full 180-day exclusivity period depends on when those 
333  ANDAs are approved in relation to when the 180-day exclusivity period is triggered.38   
334   
335  Q11.  Can there be different first applicants for different strengths of a drug product? 
336   
337  Yes.  Separate 180-day exclusivity periods are available for each strength of the same drug 
338  product, because each strength is a distinct drug product.  Thus, it is possible for there to be 
339  different first applicants for different strengths of the RLD.  For example, assume ANDA A 
340  applicant submitted the first substantially complete application that contained a paragraph IV 
341  certification for a 30 mg strength RLD and lawfully maintained that certification.  A few days 
342  later, ANDA B applicant submitted its ANDA containing a paragraph IV certification for the 30 
343  mg strength RLD.  The Agency then approves a 60 mg strength RLD, and lists a patent in the 
344  Orange Book submitted by the NDA holder for that strength.  ANDA B applicant amends its 
345  ANDA to include the 60 mg strength and includes the first paragraph IV certification to the 
346  patent listed for the 60 mg strength and lawfully maintains that certification.  ANDA A applicant 
                                                 
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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347  similarly amends its ANDA to include the 60 mg strength, but three days later.  In these 
348  circumstances, ANDA A applicant is the first applicant for the 30 mg strength, and ANDA B 
349  applicant is the first applicant for the 60 mg strength. 
350   
351  C.  180-day Exclusivity and Patents 
352   
353  Q12.   Does an ANDA applicant need to win its patent litigation to be considered a first 
354  applicant that retains eligibility for 180-day exclusivity?   
355   
356  No.  An applicant potentially may retain eligibility for 180-day exclusivity even if it is not sued 
357  as a result of its qualifying paragraph IV certification or, if sued, the case is resolved, for 
358  example, through settlement that allows the applicant to enter the market before the patent 
359  expires.39  
360   
361  Q13.  Can a patent that an NDA holder requests to remove from the Orange Book still 
362  give rise to 180-day exclusivity? 
363   
364  Yes.  An NDA holder can request that FDA remove a patent from the Orange Book in certain 
365  circumstances: for example, if a court declared the patent invalid.  However, if an NDA holder 
366  requests that a patent be removed from the Orange Book and one or more first applicants are 
367  already eligible for 180-day exclusivity based on a paragraph IV certification to that patent, FDA 
368  will not remove the patent until any 180-day exclusivity stemming from the listed patent has 
369  expired, or has been extinguished or relinquished.40  Until the patent is removed from the Orange 
370  Bookafter any associated 180-day exclusivity has expired or has been extinguished or 
371  relinquishedANDA applicants must submit or maintain appropriate certifications to the patent 
372  notwithstanding the NDA holders request to remove the patent.  This practice ensures that NDA 
373  holders cannot unilaterally extinguish an ANDA applicants eligibility for 180-day exclusivity 
374  by requesting removal of the patent from the Orange Book prior to ANDA approval.41  In such 
375  circumstances, FDA will indicate in the Orange Book that the NDA holder has requested 
376  removal of the patent.42 
377   
378  Q14.  Does an ANDA applicant retain 180-day exclusivity after the qualifying patent 
379  expires? 
380   
381  No.  In keeping with the statutory language and purpose of 180-day exclusivity, FDA has 
382  construed the statute such that 180-day exclusivity attaches based only on paragraph IV 
383  certifications to unexpired patents.   A paragraph IV certification does not survive the expiry of a 
384  listed patent.  Upon patent expiry, the statute and FDAs regulations require ANDA applicants to 
                                                 
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 FDAs 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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385  amend their certifications from a paragraph IV certification to a paragraph II certification, which 
386  states that the patent has expired.43  If an applicant neglects to amend its certification to a 
387  paragraph II certification after a patent expires, FDA will construe the application as including a 
388  paragraph II certification.44  As noted above, applications with only paragraph II certifications 
389  are eligible for immediate effective approval.45   Therefore, once the only qualifying patent 
390  expires, there are no longer any ANDAs blocked by 180-day exclusivity.   
391   
392  This interpretation of the statute effectuates the goals of the Hatch-Waxman Amendments.  The 
393  180-day exclusivity provisions were drafted to give ANDA applicants an incentive to be the first 
394  to challenge a listed patent, potentially removing that patent as a barrier to approval.  Once a 
395  listed patent expires and is no longer a barrier to ANDA approval, there is no longer a need to 
396  provide an incentive to challenge it in court.  Thus, an expired patent does not serve as the basis 
397  for a 180-day exclusivity award, and 180-day exclusivity does not extend beyond the life of the 
398  patent.   
399   
400  D.  180-day Exclusivity Trigger and Scope of 180-Day Exclusivity 
401   
402  Q15.   How is 180-day exclusivity triggered? 
403   
404  The FD&C Act provides that the 180-day exclusivity period is triggered by first commercial 
405  marketing of the drug (including the commercial marketing of the listed drug) by any first 
406  applicant.46  FDA has interpreted the statutory phrase including the commercial marketing of 
407  the listed drug to provide that exclusivity can be triggered by the marketing of an authorized 
408  generic47 by a first applicant, even if that first applicants ANDA has not yet been approved.   
409   
410  Concluding that 180-day exclusivity is triggered upon the first applicants commercial marketing 
411  of an authorized generic or the RLD prevents potential subversion of the statutory scheme 
412  through collusion between NDA holders and first applicants.  If 180-day exclusivity were 
413  triggered only by commercially marketing the first applicants ANDA product, a first applicant 
414  that struck a deal with the NDA holder to commercially market the authorized generic or RLD 
                                                 
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 applicants 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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415  instead of marketing the product described in its ANDA potentially could block approval of 
416  subsequent ANDAs until patent expiration. 
417   
418  Q16.  Once triggered, can 180-day exclusivity be suspended or postponed? 
419   
420  Once triggered, the 180-day period runs without interruption.    
421   
422  Q17.  How does the trigger of the 180-day exclusivity period by one first applicant affect 
423  other first applicants? 
424   
425  The effect of one first applicants trigger of the 180-day exclusivity period on other first 
426  applicants flows from the fact that there is only one exclusivity period available for each drug 
427  product (see Question 10 above).  Any first applicants trigger of the exclusivity period triggers 
428  the 180-day exclusivity period for all first applicants for that drug product and exclusivity for all 
429  first applicants ends 180 days after the initial trigger.  Other first applicants will benefit from 
430  exclusivity only to the extent they commercially market during this exclusivity period.  The 
431  following examples illustrate how shared 180-day exclusivity might operate.  Assume ANDA A, 
432  ANDA B, and ANDA C all qualified as first applicants.   
433   
434    If all three ANDAs are approved on the same day, and if all three first commercially 
435  market that same day, triggering the exclusivity period, all three applicants benefit from 
436  the full 180-day exclusivity period.   
437    If all three ANDAs are approved on the same day, but only ANDA A is commercially 
438  marketed on that first day triggering the exclusivity period, it is triggered for all three 
439  ANDAs.  Thus, if ANDA B is not commercially marketed until day 30, that applicant 
440  will benefit from exclusivity only for the remainder of the 180-day period (i.e., 150 days).  
441  If ANDA C is not commercially marketed until day 179, it will benefit from only one day 
442  of exclusivity.   
443    If one or more ANDAs are approved on the same day, but one or more applicants first 
444  commercially market the drug product 60 days after approval, the 180-day exclusivity 
445  period is triggered upon commercial marketing and runs for 180 days.   
446   
447  Q18.  Does 180-day exclusivity block approval of all ANDAs that reference the same 
448  RLD? 
449   
450  No.  180-day exclusivity blocks only the approval of subsequent ANDAs that also contain a 
451  paragraph IV certification.48  There are several examples in which 180-day exclusivity does not 
452  block approval of another ANDA referencing the same RLD: 
453   
454    If an ANDA was approved before the NDA holder submitted a patent that provides the 
455  basis for first applicant status for a pending ANDA, any related 180-day exclusivity 
456  would not affect the previously approved ANDA. 
                                                 
48 See section 505(j)(5)(B)(iv)(I) of the FD&C Act. 
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457    If an ANDA applicant seeks to omit the approved method(s) of use covered by a listed 
458  patent with a section viii statement, another ANDA applicants paragraph IV certification 
459  to that same patent, and any related 180-day exclusivity, would not block approval of the 
460  ANDA that contained the section viii statement. 
461    If a patent was late-listed vis-a-vis a pending ANDA under FDAs regulations, a first 
462  applicants paragraph IV certification to that patent, and any related 180-day exclusivity, 
463  would not block approval of the ANDA for which the patent is late-listed and for which 
464  as a result no patent certification was required.49 
465   
466  Q19.  Can an authorized generic be marketed during the 180-day exclusivity period?   
467   
468  Yes.  180-day exclusivity only blocks approval of subsequent applicants ANDAs under section 
469  505(j) of the FD&C Act and does not affect the approval of or marketing under NDAs, including 
470  marketing of authorized generics.   
471   
472  Q20.  Can pediatric exclusivity affect the timing of approval of subsequent applicants 
473  ANDAs after the 180-day exclusivity period is triggered? 
474   
475  Yes.  Under section 505A(b)(1)(B)(i) of the FD&C Act (addressing pediatric exclusivity), if 
476  pediatric exclusivity attaches to a listed patent, the period during which an ANDA may not be 
477  approved under section 505(j)(5)(B) of the FD&C Act may be extended by 6 months after the 
478  date the patent expires.  An ANDA with a paragraph IV certification is required to change its 
479  certification to a paragraph II certification when the patent expires (and will be treated as 
480  containing a paragraph II certification even if it fails to affirmatively change its certification). 
481  Under section 505A(b)(1)(B)(i)(I), an ANDA that was previously blocked by another applicants 
482  eligibility for 180-day exclusivity and that must change to a paragraph II certification (when the 
483  patent that formed the basis of the exclusivity expires) will be blocked from approval by 
484  pediatric exclusivity after the qualifying patent (and any associated 180-day exclusivity) has 
485  expired.  
486   
487  For example, a first applicants ANDA contains a paragraph IV certification to a patent that has 
488  an associated 6-month period of pediatric exclusivity.  The ANDA is approved 178 days before 
489  the patent expires, immediately commences commercial marketing, and enjoys 178 days of the 
490  180-day exclusivity.  The patent expires, all ANDAs that have not yet been approved must 
491  change to paragraph II certification to that patent, the 6-month pediatric exclusivity period 
492  commences, and FDA generally cannot approve any ANDA with a paragraph II certification 
493  during the 6-month pediatric exclusivity period.  Because the first applicant was approved prior 
                                                 
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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494  to the start of pediatric exclusivity, it does not need to change its certification upon patent expiry 
495  and pediatric exclusivity does not affect the approval of the first applicants ANDA.  However, 
496  any subsequent applicants ANDA will need to contain a paragraph II certification and will not 
497  be eligible for approval until the pediatric exclusivity expires.  Thus, the first applicant may 
498  enjoy an additional six months of de facto exclusivity before FDA can approve another ANDA.  
499    
500  E.  180-day Exclusivity Relinquishment and Waiver 
501   
502  Q21.  Can a first applicant relinquish or waive its 180-day exclusivity? 
503   
504  Yes.  FDA has consistently interpreted section 505(j)(5)(B)(iv) of the FD&C Act to permit both 
505  relinquishment and selective waiver of 180-day exclusivity.  Relinquishment refers to the 
506  voluntary and complete abandonment of eligibility for exclusivity.  Selective waiver refers to a 
507  first applicants waiver of exclusivity to permit approval during the exclusivity period of a 
508  particular subsequent ANDA, or subsequent ANDAs.  Relinquishment and selective waiver of 
509  180-day exclusivity promote the purpose of the exclusivityto encourage patent challenges and 
510  increase marketplace competition.   
511   
512  A first applicant that is eligible for 180-day exclusivity may relinquish its exclusivity at any time.  
513  In contrast, selective waiver of 180-day exclusivity may occur only once the exclusivity period 
514  has been triggered.  
515   
516  Q22.  Will subsequent applicants be notified if 180-day exclusivity is selectively waived or 
517  relinquished? 
518   
519  As a general matter, when all first applicants have relinquished their claims to 180-day 
520  exclusivity, FDA may inform subsequent applicants that are otherwise eligible for approval that 
521  their ANDAs may be approved. 
522   
523  For selective waivers, FDAs practice is to notify only the subsequent applicant in whose favor 
524  the exclusivity has been waived.  If a first applicants exclusivity were triggered and selectively 
525  waived in favor of a subsequent applicant with an unapproved ANDA, the fact of the selective 
526  waiver to the subsequent applicant could be considered information in the unapproved ANDA.  
527  As such, FDA generally would not disclose that the selective waiver had occurred to anyone 
528  except the applicant in whose favor exclusivity was waived, at least until the ANDA benefited by 
529  the waiver was approved.50   
530   
531  F.  Forfeiture of 180-day Exclusivity 
532   
533  Q23.  How does FDA determine whether a first applicant has forfeited its eligibility for 
534  180-day exclusivity? 
535   
536  To ascertain whether a first applicant has forfeited eligibility for 180-day exclusivity, FDA looks 
537  at the qualifying patent(s) to determine whether the applicant has lawfully maintained its 
                                                 
50 See 21 CFR 314.430(d)(1).   
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538  paragraph IV certification(s) and whether the applicant has forfeited exclusivity under any of the 
539  forfeiture provisions, as discussed below.   
540   
541  1.  Failure to Market Forfeiture Provision  
542   
543  Section 505(j)(5)(D)(i)(I) states that a forfeiture event occurs: 
544  (I)  If the first applicant fails to market the drug by the later of- 
545  (aa) the earlier of the date that is- 
546  (AA) 75 days after the date on which the approval of the application of the 
547  first applicant is made effective [...]; or 
548  (BB) 30 months after the date of submission of the application of the first 
549  applicant; or 
550  (bb) with respect to the first applicant or any other applicant (which other 
551  applicant has received tentative approval), the date that is 75 days after the date as 
552  of which, as to each of the patents with respect to which the first applicant 
553  submitted and lawfully maintained a certification qualifying the first applicant for 
554  the 180-day exclusivity period [...], at least one of the following has occurred: 
555  (AA) In an infringement action brought against that applicant with respect 
556  to the patent or in a declaratory judgment action brought by that applicant 
557  with respect to the patent, a court enters a final decision from which no 
558  appeal (other than a petition to the Supreme Court for a writ of certiorari) 
559  has been or can be taken that the patent is invalid or not infringed. 
560  (BB) In an infringement action or a declaratory judgment action described 
561  in subitem (AA), a court signs a settlement order or consent decree that 
562  enters a final judgment that includes a finding that the patent is invalid or 
563  not infringed.  
564  (CC) The patent information submitted under subsection (b) or (c) is 
565  withdrawn by the holder of the application approved under subsection 
566  (b).51 
567  Q24.  How does FDA determine whether a first applicant has forfeited exclusivity under 
568  the failure to market provision? 
569   
                                                 
51 Section 505(j)(5)(D)(i)(I) of the FD&C Act. 
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570  Determining whether forfeiture has occurred requires analyzing if and when the events described 
571  under the failure to market provision occurred.  As seen in the statutory provision outlined 
572  immediately above, application of this forfeiture provision requires a series of analyses based on 
573  the timing of specific events.  The statute directs that a forfeiture event occurs when the first 
574  applicant fails to market the drug by the later of two dates.  One of these dates is calculated under 
575  item (aa) by determining the earlier of a date that is either 75 days after the first applicants 
576  ANDA is approved (subitem (AA)) or 30 months after the date of submission of the first 
577  applicants ANDA (subitem (BB)).  The date determined under item (aa) then is compared to the 
578  date as determined under item (bb).  Item (bb) states that the occurrence of at least one of the 
579  enumerated events with respect to a first applicant or any other applicant (which other applicant 
580  has received tentative approval) as to each of the qualifying patents will begin a 75-day period 
581  leading to possible forfeiture of exclusivity.  These events include, very generally, when a court 
582  enters a final decision that the patent is invalid or not infringed, a court signs a settlement order 
583  or consent decree entering final judgment that includes a finding that the patent is invalid or not 
584  infringed, or the patent information for the listed drug is withdrawn by the NDA holder.52  For an 
585  event to occur under item (bb) by any other applicant, the same other applicant must receive both 
586  tentative approval and a final court decision described in subitem (AA) or (BB).  Forfeiture 
587  under section 505(j)(5)(D)(i)(I) of the FD&C Act occurs if the first applicant fails to market by 
588  the later of the dates under item (aa) or (bb).   
589   
590  A hypothetical example illustrates how FDA determines whether forfeiture has occurred under 
591  the failure to market provision.  For the purposes of evaluating item (aa), presume that on June 
592  1, 2009, the applicant for ANDA A submitted its substantially complete application containing a 
593  paragraph IV certification, which it lawfully maintained.  FDA approved the ANDA on 
594  December 20, 2012, and the 75-day period identified in subitem (AA) of this forfeiture provision 
595  ended on March 4, 2013.  Thirty months after the date the ANDA is submitted was December 1, 
596  2011 (the date identified in subitem (BB)).53  The relevant date for item (aa) of the forfeiture 
597  analysis is December 1, 2011, the earlier of these two dates.   
598   
599  For the second part of the analysis under item (bb), presume that on January 1, 2013, a court 
600  entered a final decision (from which no appeal (other than a petition to the Supreme Court for a 
601  writ of certiorari) has been or can be taken) that the relevant patent is invalid and not infringed in 
602  an infringement action against a subsequent applicant for this RLD whose ANDA received 
603  tentative approval at some point before FDA makes the forfeiture determination.  The relevant 
604  forfeiture date for ANDA A pursuant to subitem (AA) is March 17, 2013, 75 days after the date 
605  on which the court issued its decision.  Notably, this date applies even though ANDA A in this 
606  example was not the subject of the litigation.   
607   
608  In this scenario, the failure to market forfeiture provision requires the first applicant to market by 
609  March 17, 2013, the later of the dates applicable under item (aa) (December 1, 2011) and item 
                                                 
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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610  (bb) (March 17, 2013).  In this example, if ANDA A applicant did not begin commercial 
611  marketing until after March 17, 2013, it would forfeit its exclusivity. 
612   
613  Q25.  Does an event from both items (aa) and (bb) of the failure to market provision 
614  have to occur to result in forfeiture under this provision? 
615   
616  Yes.  The failure to market provision results in forfeiture when there are two dates (one from 
617  item (aa) and one from item (bb)) on the basis of which FDA may identify the later event as 
618  described in section 505(j)(5)(D)(i)(I) of the FD&C Act.  The provision does not effect a 
619  forfeiture when an event under item (aa) has occurred, but no event under item (bb) has yet 
620  occurred. 
621   
622  Q26.  Does an NDA holders request to remove the qualifying patent from the Orange 
623  Book qualify as a triggering event under subitem (bb)(CC)? 
624   
625  No.  An NDA holders request that the qualifying patent be removed from the Orange Book does 
626  not constitute an event under subitem (CC) because as described in Question 13, FDA will not 
627  remove a patent from the Orange Book if the removal would deprive a first applicant of 180-day 
628  exclusivity to which it is otherwise entitled.  This policy prevents an NDA holder from removing 
629  a qualifying patent in order to deprive a first applicant of the period of 180-day exclusivity for 
630  which it is otherwise eligible.54 
631   
632  2.  Withdrawal of Application Forfeiture Provision  
633   
634  A forfeiture event occurs under this provision if [t]he first applicant withdraws the application 
635  or [FDA] considers the application to have been withdrawn as a result of [FDAs] determination 
636  . . . that the application does not meet the requirements for approval under [section 505(j)(4) of 
637  the FD&C Act].55 
638   
639  Q27.  How does FDA determine forfeiture under the withdrawal of application 
640  forfeiture provision? 
641   
642  The withdrawal of application provision provides for forfeiture under two conditions: (1) if the 
643  first applicant withdraws the application or (2) if FDA considers the application withdrawn for 
644  failure to meet the various general requirements for approval laid out in section 505(j)(4) of the 
645  FD&C Act.  A first applicants affirmative withdrawal of its ANDA would meet the first 
646  condition, resulting in a forfeiture under this provision.  FDA has not yet considered a forfeiture 
647  under the second condition. 
648   
649  3.  Amendment of Certification Forfeiture Provision  
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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651  A forfeiture event occurs under this provision if [t]he first applicant amends or withdraws the 
652  certification for all of the patents with respect to which that applicant submitted a certification 
653  qualifying the applicant for the 180-day exclusivity period.56 
654   
655  Q28.  How does FDA determine forfeiture under the amendment of certification 
656  forfeiture provision? 
657   
658  This subsection provides for forfeiture when a first applicant amends or withdraws the paragraph 
659  IV certification for all of the patents or claims of patent(s) for which that applicant submitted a 
660  paragraph IV certification qualifying the applicant for the 180-day exclusivity period.  For 
661  instance, forfeiture under this provision occurs when the ANDA applicant loses related patent 
662  litigation and amends its ANDA to include a paragraph III certification to all of the qualifying 
663  patents.57  As noted above, FDA regulations require ANDA applicants to amend their patent 
664  certification if, at any time before the date of approval of the ANDA, the applicant learns that 
665  the submitted certification or statement is no longer accurate.58  FDA recommends that 
666  applicants provide this information to the Agency expeditiously to avoid unnecessary 
667  expenditure of resources in considering forfeiture on other grounds.   
668   
669  Notably, this forfeiture provision does not require a first applicant to have amended or 
670  withdrawn all paragraph IV certifications contained in its ANDA to forfeit, just those that 
671  qualified the applicant as a first applicant.  Accordingly, a first applicant may forfeit its 
672  eligibility for exclusivity under this provision, but still maintain paragraph IV certifications to 
673  non-qualifying patents.  For example, an ANDA applicant submits a substantially complete 
674  ANDA with a paragraph IV certification to patent 1 (the only patent listed at that time) and later 
675  amends its ANDA to contain a paragraph IV certification to patent 2, which was newly issued by 
676  the U.S. Patent and Trademark Office and timely submitted for listing in the Orange Book.  If the 
677  ANDA applicant withdraws its paragraph IV certification to patent 1, it will forfeit its eligibility 
678  for 180-day exclusivity even though the applicant maintains its paragraph IV certification to 
679  patent 2.  If, on the other hand, the ANDA applicant withdraws its paragraph IV certification to 
680  patent 2, but maintains its paragraph IV certification to patent 1, eligibility for 180-day 
681  exclusivity will not be affected. This is because only patent 1 qualified the ANDA applicant for 
682  180-day exclusivity.  
683   
684  Q29.  Does a first applicant forfeit exclusivity under the amendment of certification 
685  provision when, because of a change in formulation of the proposed generic drug, a first 
686  applicant is required to resubmit paragraph IV certifications to the qualifying patents?   
687   
688  No.  Resubmission of paragraph IV certifications in connection with an ANDA applicants 
689  reformulation of its proposed drug product does not constitute an amendment or withdrawal of 
690  the paragraph IV certifications under this forfeiture provision.  FDA requires submission of an 
691  appropriate patent certification or, for a previously submitted paragraph IV certification, a 
692  recertification, in certain circumstances.  For example, an appropriate patent certification or 
                                                 
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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693  statement or a recertification is required, among other bases, when an applicant amends its 
694  ANDA to make other than minor changes in product formulation.59  This practice provides 
695  notice of the proposed change in formulation of the ANDA product to the NDA holder and each 
696  patent owner so that any patent issues related to the new formulation can be resolved.  Under 
697  applicable regulations, recertification does not constitute an amendment or withdrawal of the 
698  paragraph IV certification resulting in forfeiture of 180-day exclusivity.  Rather, an ANDA 
699  applicants resubmission of paragraph IV certifications in connection with reformulation is 
700  understood to fulfill the statutory requirement to continuously maintain previous paragraph IV 
701  certifications to those patents.60  As explained in the final rule on Abbreviated New Drug 
702  Applications and 505(b)(2) Applications, a subsequent paragraph IV certification to the 
703  qualifying patent or patent claim is not an amendment of the previously submitted paragraph 
704  IV certification under section 505(j)(5)(D)(i)(III) of the FD&C Act because the type of 
705  certification remains the same; rather, it is a reaffirmation of the patent challenge 
706  notwithstanding the amendment to the ANDA.61 
707   
708  Q30.  Does a license agreement between the first applicant and the NDA holder or patent 
709  owner constitute an amendment of certification under this provision? 
710   
711  No.  FDAs regulations provide that a paragraph IV certification remains appropriate if the basis 
712  for non-infringement (of an otherwise valid and infringed patent) is that the ANDA applicant has 
713  obtained a license from the patent owner with respect to the patent.62   
714   
715  Nor does an ANDA applicants agreement that the qualifying patent is valid and would be 
716  infringed in the course of securing a license require the applicant to change the paragraph IV 
717  certification to a paragraph III certification, because requiring such a certification change would 
718  render the license null.  The effect of a paragraph III certification is that the ANDA cannot be 
719  approved until the patent expires.  If required to change its paragraph IV certification to a 
720  paragraph III certification, the ANDA applicant licensee could not have an approved generic 
721  drug product to market during the period in which it needed and obtained a license to do so.  
722   
723  4.  Failure to Obtain Tentative Approval Forfeiture Provision  
724   
725  A forfeiture event occurs under this provision if [t]he first applicant fails to obtain tentative 
726  approval of the application within 30 months after the date on which the application is filed, 
727  unless the failure is caused by a change in or a review of the requirements for approval of the 
728  application imposed after the date on which the application is filed.63 
729   
730  Q31.  How are the dates of the 30-month forfeiture period determined? 
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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732  The starting date of the 30-month period64 in which a first applicant must obtain tentative or final 
733  approval or risk forfeiture is one day after the date that a first applicant submits its substantially 
734  complete application.65  The last day of the 30-month period lands on the 30-month anniversary 
735  date of ANDA submission.  For example, for an ANDA filed on February 10, 2005, the 30-
736  month period began on February 11, 2005, and the last day of the 30-month period was August 
737  10, 2007.66 
738   
739  We note that the day after the date of a first applicants ANDA submission is the date used to 
740  determine the start of the 30-month forfeiture period even if the ANDA originally did not contain 
741  a paragraph IV certification, but was amended later to contain one that qualified the applicant as 
742  a first applicant.  Thus, it is possible that FDA could determine that an applicant forfeited its 
743  eligibility for exclusivity under this provision based on the 30-month period beginning before 
744  submission of a paragraph IV certification. 
745   
746  The Food and Drug Administration Safety and Innovation Act67 (FDASIA) created an exception 
747  to this general rule regarding the 30-month forfeiture period and paragraph IV certifications 
748  submitted in an amendment.  The law provides that for applications submitted on or before July 
749  9, 2012, and amended to first contain a paragraph IV certification between July 10, 2012, and 
750  September 30, 2017, the 30-month forfeiture period begins the day after the date of submission 
751  of the paragraph IV amendment, rather than the day after the date of submission of the 
752  substantially complete ANDA.68   
753   
754  Q32.  Is the 30-month forfeiture period ever extended or modified?   
755   
756  Yes.  First, subsection 505(q)(1)(G) of the FD&C Act, enacted as part of the Food and Drug 
757  Administration Amendments Act of 2007,69 concerns the submission of citizen petitions that 
758  relate to already pending ANDAs and provides that [i]f the filing of an application resulted in 
759  first-applicant status under subsection (j)(5)(D)(i)(IV) and approval of the application was 
760  delayed because of a petition, the 30-month period under such subsection is deemed to be 
761  extended by a period of time equal to the period beginning on the date on which [FDA] received 
762  the petition and ending on the date of final agency action on the petition (inclusive of such 
763  beginning and ending dates), without regard to whether [FDA] grants, in whole or in part, or 
764  denies, in whole or in part, the petition.  Thus, pursuant to this provision, if approval of a first 
765  applicants ANDA was delayed because of a petition submitted under section 505(q) of the 
                                                 
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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766  FD&C Act70 such that the time it took FDA to respond to the 505(q) petition prevented approval 
767  within 30 months from the date of submission, the 30-month deadline for obtaining a tentative or 
768  final approval will be extended by the amount of time the 505(q) petition was under review. 
769   
770  Second, section 1133(a) of FDASIA extended the 30-month period for certain ANDAs.  Under 
771  FDAs interpretation of these provisions, for applications submitted between January 9, 2010, 
772  and July 9, 2012, containing a paragraph IV certification (or amended to first contain a paragraph 
773  IV certification during that period of time), and approved or tentatively approved during the 
774  period of time beginning on July 9, 2012, and ending on September 30, 2015, section 1133(a) of 
775  FDASIA extended this period to 40 months.  For applications submitted between January 9, 
776  2010, and July 9, 2012 (or amended to first contain a paragraph IV certification during that 
777  period of time), and approved or tentatively approved during the period of time beginning on 
778  October 1, 2015, and ending on September 30, 2016, section 1133(a) of FDASIA extended this 
779  period to 36 months.  In addition, if an application was submitted between January 9, 2010, and 
780  July 9, 2012 containing a paragraph IV certification (or amended to first contain a paragraph IV 
781  certification during that period of time), and FDA had not approved or tentatively approved the 
782  application but must consider whether the applicant had forfeited exclusivity because a 
783  potentially blocked application is ready for approval, FDA applied the 36-month period if it 
784  made the forfeiture determination between the period of time beginning on October 1, 2015, and 
785  ending on September 30, 2016.  For all other applications, the 30-month period set forth in 
786  section 505(j)(5)(D)(i)(IV) of the FD&C Act applies.   
787   
788  Q33.  Does the failure to obtain tentative approval forfeiture provision apply to 
789  circumstances in which the first applicant was not eligible for tentative approval but failed 
790  to obtain final approval by the 30-month forfeiture date? 
791   
792  Yes.  Unless the 30-month period is extended for one of the reasons described above,71 a first 
793  applicant that fails to obtain either tentative approval or final approval of its ANDA by the 30-
794  month forfeiture date generally will forfeit eligibility for 180-day exclusivity.  Viewed in 
795  isolation, the phrase tentative approval in section 505(j)(5)(D)(i)(IV) of the FD&C Act might 
796  suggest that this section applies only when an ANDA is eligible for a tentative approval due to a 
797  patent, 30-month stay, or exclusivity blocking final approval.  Such a reading of the statute 
798  would result in incongruous circumstances in which first applicants that are eligible for tentative 
799  approval can forfeit under this provision, but first applicants that only are eligible for final 
800  approval (and arguably closer to marketing) cannot forfeit under this provision.  Other references 
801  to this forfeiture provision in the statute make clear that the provision has a broader scope.  For 
802  example, section 505(q)(1)(G) of the FD&C Act expressly states that if approval of the first 
803  applicants application was delayed because of a petition, the 30-month period described in 
804  section 505(j)(5)(D)(i)(IV) of the FD&C Act will be extended.  In light of this language, FDA 
805  has concluded that section 505(j)(5)(D)(i)(IV) establishes a 30-month period within which a first 
806  applicant generally must obtain either tentative approval or final approval of its ANDA.  This 
807  interpretation squares both with the statutory language and with the statutory purpose of 
                                                 
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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808  preventing first applicants ANDAs that do not meet the substantive requirements for approval 
809  from delaying approval of subsequent applicants ANDAs.   
810   
811  Q34.  How does a first applicant qualify for the exception in the failure to obtain 
812  tentative approval forfeiture provision? 
813   
814  To qualify for the exception to this forfeiture provision, the failure to obtain tentative or final 
815  approval must be caused by a change in or a review of the requirements for approval of the 
816  application imposed after the date on which the application is filed.72  In other words, two 
817  conditions must both be met: (1) FDA changed or reviewed (i.e., considered whether to change) 
818  the requirements for approval while the application was under review and (2) this change in, or 
819  review of, approval requirements was a cause of the failure to obtain tentative approval or final 
820  approval by the 30-month forfeiture date.  However, FDA has determined that but-for 
821  causation is not required to qualify for this exception.  In other words, if one of the causes of 
822  failure to obtain tentative or final approval by the 30-month forfeiture date was a change in or 
823  review of the requirements for approval imposed after the application was filed, an applicant will 
824  not forfeit eligibility for exclusivity notwithstanding that there may have been other causes for 
825  failure to obtain tentative approval or final approval by the 30-month forfeiture date.  
826  Consequently, to qualify for the exception, the record must show that acceptability of at least one 
827  aspect of the ANDA (e.g., bioequivalence) was delayed and, irrespective of what other review 
828  issues may have been outstanding at the 30-month date, that this delay was caused, at least in 
829  part, by a change in, or review of, the requirements for approval.  FDA has determined that this 
830  interpretation of the statute best effectuates the policy underlying the exception.  It does not 
831  penalize applicants for FDAs reviews of, or changes in, approval requirements imposed on 
832  applicants after their ANDAs are filed that are a cause of the failure to obtain final approval or 
833  tentative approval within 30 months.  This interpretation also continues to incentivize ANDA 
834  applicants to challenge patents by preserving in many instances the opportunity to obtain 180-
835  day exclusivity. 
836   
837  Q35.  Can a first applicant qualify for the exception if, at the 30-month forfeiture date, 
838  FDA is reviewing an ANDA amendment submitted to address a change in the requirements 
839  for approval?  
840   
841  Yes.  FDA generally will presume that failure to obtain tentative approval or final approval was 
842  caused by a change in, or review of, approval requirements if, at the 30 month date, the evidence 
843  demonstrates that there was a change in, or review of, the requirements for approval and that the 
844  applicant was actively addressing issues related to the change in, or review of, approval 
845  requirements (or FDA was considering such efforts), and these efforts precluded tentative 
846  approval or final approval at that time.  When the evidence fails to demonstrate that the applicant 
847  was actively addressing the change in, or review of, approval requirements, and that these 
848  activities precluded tentative approval or final approval at the 30-month date, FDA generally 
849  does not presume that the failure was caused by a change in, or review of, approval 
850  requirements.  If FDA were to hold otherwise, an applicant that receives one or more 
851  deficiencies resulting from a change in approval requirements could avoid forfeiture by a delay 
                                                 
72 Section 505(j)(5)(D)(i)(IV) of the FD&C Act. 
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852  in addressing those deficiencies.  When evaluating causation for purposes of determining 
853  forfeiture under this provision, FDA will take into account how close the change in or review of 
854  the requirement for approval occurred to the 30-month date as well as the amount of effort 
855  needed to respond to the change.  Further, if the applicants response is submitted after the 30-
856  month date, FDA will consider, among other factors, how close the response is submitted to the 
857  30-month date.   
858   
859  Q36.  Does the exception to the failure to obtain tentative approval forfeiture provision 
860  apply if FDAs review of an ANDA takes longer than 30 months in the absence of a change 
861  in or review of the approval requirements?   
862   
863  No.  Under this forfeiture provision, exclusivity is forfeited unless there is a review of or 
864  change in the approval requirements that has delayed final approval or tentative approval of the 
865  ANDA.  The statute does not permit FDA to consider an exception based on whether the 
866  application could have received tentative approval or final approval before the 30-month 
867  forfeiture date had FDAs review been conducted differently.  Section 1133 of FDASIA 
868  (referenced in Question 32), which, among other things, extended the 30-month forfeiture period 
869  to 40 months for certain ANDAs and to 36 months for certain other ANDAs, reflects Congresss 
870  understanding that, even in the absence of a change in or review of the requirements for 
871  approval, FDAs review of an ANDA might take more than 30 months and might contribute to a 
872  first applicants failure to obtain tentative approval or final approval by the 30-month forfeiture 
873  date and result in forfeiture of exclusivity.  
874   
875  Q37.  What are examples of changes in the requirements for approval that formed the 
876  basis of an exception to the failure to obtain tentative approval forfeiture provision? 
877   
878  The following are examples of changes in the requirements for approval imposed after ANDA 
879  submission that FDA has determined were a cause of failure to obtain tentative or final approval 
880  in 30 months and therefore formed the basis of an exception to this forfeiture provision:   
881   
882    FDAs change in approval requirements related to drug quality that required an applicant 
883  to conduct additional testing and include an additional new drug substance specification; 
884    FDAs change in approval requirements for demonstrating bioequivalence for a drug 
885  product; 
886    Changes in the RLD labeling that required changes in the ANDA applicants generic 
887  drug labeling; 
888    Changes in an RLDs formulation that required an ANDA applicant to respond (for 
889  example, by seeking approval for a change in formulation); and 
890    The publication in the United States Pharmacopeia-National Formulary of a final 
891  monograph for a drug product making it necessary for applicants to demonstrate 
892  compliance with the new compendial standards.73 
                                                 
73 This list is intended to be illustrative and not exhaustive.   
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893   
894  Q38.  Can FDAs review of an approval requirement result in an exception to the failure 
895  to obtain tentative approval forfeiture provision even if the approval requirements 
896  ultimately do not change? 
897   
898  Yes.  FDAs review, without change, of approval requirements can be a cause of failure to obtain 
899  tentative or final approval within 30 months.   
900   
901  For example, assume FDA originally determines a particular bioequivalence method to be 
902  acceptable for a tablet dosage form.  Sometime before the 30-month forfeiture date, FDA 
903  identifies concerns related to certain dissolution data for one or more tablet products and decides 
904  to ask pending ANDAs to develop and propose a different dissolution method, which the 
905  applicants provide.  After the 30-month forfeiture date, FDA asks a first applicant that had 
906  proposed a modified dissolution method to repeat its dissolution testing for all strengths of the 
907  companys drug product using the new method.  The first applicant submits an amendment with 
908  the dissolution data derived from the modified method.  FDA ultimately determines after the 
909  forfeiture date that FDAs originally recommended dissolution method was appropriate.  
910  Because FDAs review of the bioequivalence requirements was a cause of the failure to obtain 
911  timely tentative or final approval, the exception to the failure to obtain tentative approval 
912  forfeiture provision would still apply even though FDA ultimately did not change the dissolution 
913  methods. 
914   
915  Q39.  Can FDAs consideration of issues raised in a citizen petition related to the 
916  requirements for ANDA approval provide the basis of an exception to the forfeiture 
917  provision if an ANDA is submitted after the petition is submitted and is reviewed while that 
918  petition is pending? 
919   
920  Yes, assuming the other criteria for the exception are met.  Specifically, if the review of issues 
921  raised in a petition submitted before submission of the first applicants ANDA continues after 
922  ANDA submission and during ANDA review, FDAs consideration of the issues raised in the 
923  petition can constitute a change in or review of requirements for approval. 
924   
925  5.  Agreement with Another ANDA Applicant, the Listed Drug Application Holder, or a 
926  Patent Owner  
927   
928  A forfeiture event occurs under this provision if [t]he first applicant enters into an agreement 
929  with another applicant [...] for the drug, the holder of the application for the listed drug, or an 
930  owner of the patent that is the subject of [a paragraph IV] certification [...], the Federal Trade 
931  Commission or the Attorney General files a complaint, and there is a final decision of the 
932  Federal Trade Commission or the court with regard to the complaint from which no appeal (other 
933  than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the 
934  agreement has violated the antitrust laws [...].74 
935   
                                                 
74 Section 505(j)(5)(D)(i)(V) of the FD&C Act. 
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936  Q40.  Are there examples of forfeiture under the provision related to agreements with 
937  another applicant, the NDA holder, or a patent owner? 
938   
939  No.  As of the date of publication of this draft guidance, FDA has not determined that a first 
940  applicant has forfeited its eligibility for exclusivity under this provision, sometimes referred to as 
941  the collusive agreement forfeiture provision.  We note that the collusive agreement forfeiture 
942  provision applies to all pending ANDAs, regardless of when the first ANDA referencing the 
943  RLD was submitted.75  This is not the case for the other forfeiture provisions.76  We also note 
944  that the collusive agreement forfeiture provision applies to only those settlement agreements 
945  described in the statute when, among other things, there is a final decision of the Federal Trade 
946  Commission or court that the agreement has violated the antitrust laws, and the decision cannot 
947  be or has not been appealed. 
948   
949  6.  Expiration of All Patents Forfeiture Provision  
950   
951  A forfeiture event occurs under this provision if [a]ll of the patents as to which the applicant 
952  submitted a certification qualifying it for the 180-day exclusivity period have expired.77 
953   
954  Q41.  Does forfeiture under the expiration of all patents provision require the 
955  expiration of all listed patents to which a first applicant submitted a paragraph IV 
956  certification? 
957   
958  No.  A forfeiture under this provision occurs upon expiration of only all of the qualifying 
959  patent(s).  Forfeiture can occur under this provision even if the first applicant has paragraph IV 
960  certifications to other listed patents that have not expired as long as the certification to these 
961  other patents did not provide the basis for eligibility for 180-day exclusivity.  For example, 
962  suppose an ANDA applicant is the first applicant based on the submission of a substantially 
963  complete ANDA containing a paragraph IV certification to U.S. Patent No. 3,456,879 (the 879 
964  patent).  After submission of the ANDA, U.S. Patent No. 6,789,101 (the 101 patent) for the 
965  RLD is listed and the ANDA applicant amends its application to include a paragraph IV 
966  certification to it.  The ANDA applicant will forfeit exclusivity upon expiration of the 879 
967  patent (the only qualifying patent), even if the 101 patent remains unexpired.   
968   
969  7.  Effect of Forfeiture 
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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971  Q42.  Does a first applicant that forfeited its eligibility for exclusivity become a 
972  subsequent applicant blocked from final approval by other first applicants eligibility for 
973  exclusivity?  
974   
975  No.  The FD&C Act provides that [t]he 180-day exclusivity period [...] shall be forfeited by a 
976  first applicant if a forfeiture event occurs with respect to that first applicant.78  Neither this 
977  statutory provision, nor any other, states that in forfeiting exclusivity, a first applicant becomes a 
978  subsequent applicant whose ANDA can be approved only after the 180-day exclusivity period 
979  has run.  Thus, FDA interprets the statute such that a first applicant that has forfeited exclusivity 
980  remains a first applicant and need not await expiration of 180-day exclusivity to obtain approval 
981  of its ANDA.  A first applicant that has forfeited exclusivity is subject to the same timetable for 
982  approval that governs the approval of ANDAs for first applicants that remain eligible for 180-
983  day exclusivity.79  Section 505(j)(5)(B)(iv) of the FD&C Act, which governs the running of 180-
984  day exclusivity, does not distinguish between first applicants that have forfeited eligibility for 
985  180-day exclusivity and those that have not, providing instead only that a subsequent applicants 
986  ANDA may be approved 180 days after the date of first commercial marketing by any first 
987  applicant.  In addition, once FDA has approved one or more ANDAs, commercial marketing by 
988  any first applicant will trigger the 180-day exclusivity period for all the first applicant ANDAs, 
989  even if the triggering applicant is the first applicant that forfeited its eligibility for exclusivity.   
990   
991  For example, assume ANDA A and ANDA B are first applicants.  ANDA A forfeits its 
992  eligibility for 180-day exclusivity for failure to obtain tentative approval within 30 months but 
993  ANDA B maintains its eligibility.  ANDA A is not blocked from approval by ANDA Bs 180-
994  day exclusivity because ANDA A remains a first applicant.  ANDA A also can trigger ANDA 
995  Bs 180-day exclusivity.  However, ANDA A will not itself block subsequent applicants from 
996  approval.  Only ANDA B, which retained eligibility for exclusivity, will block subsequent 
997  applicants from approval.   
998   
999  Q43.  If 180-day exclusivity is forfeited by the first applicant(s), does it roll to the next-
1000  submitted ANDA? 
1001   
1002  No.  180-day exclusivity is only available to those ANDA applicants that meet the statutory 
1003  definition of first applicant.80  Thus, any subsequent applicant that did not submit a substantially 
1004  complete ANDA that contained a paragraph IV certification on the first day such an application 
1005  was submitted does not qualify for exclusivity.  Once 180-day exclusivity is forfeited by all the 
1006  first applicants, it no longer blocks approval of any subsequent applicants ANDAs but 
1007  subsequent applicants do not become first applicants under those circumstances. 
1008   
1009   
1010  G.  Procedural Questions Regarding 180-day Exclusivity Determinations 
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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1012  Q44.  When does FDA decide whether an ANDA applicant is eligible for 180-day 
1013  exclusivity? 
1014   
1015  It is FDAs practice to make decisions on eligibility for 180-day exclusivity in the context of 
1016  specific ANDAs that are otherwise eligible for approval (i.e., when a first applicants ANDA or a 
1017  subsequent applicants ANDA is ready for approval).  Many factors may influence eligibility for 
1018  exclusivity up to the time an application is ready for approval (e.g., patent expiration, failure to 
1019  obtain a tentative or final approval within 30 months, withdrawal of ANDA) and thus could 
1020  render a premature eligibility determination incorrect.  When FDA makes an approval decision 
1021  with respect to an ANDA, it will inform an applicant affected by exclusivity of its status.  For 
1022  example, FDA generally will inform an ANDA applicant it is (1) a first applicant entitled to 
1023  exclusivity, (2) a first applicant that has forfeited its exclusivity, (3) eligible only for a tentative 
1024  approval because one or more first applicants are eligible for 180-day exclusivity, or (4) eligible 
1025  for final approval because all first applicants have forfeited exclusivity.   
1026   
1027  In some circumstances, when a first applicant is ready for final approval, FDA may refrain from 
1028  making a formal determination regarding that applicants eligibility for 180-day exclusivity.  
1029  Specifically, if FDAs review of the ANDAs for the drug product indicates that a formal 
1030  determination of eligibility for 180-day exclusivity is not necessary (e.g., if there are no 
1031  subsequent ANDAs or the subsequent ANDAs are likely more than 180 days away from final 
1032  approval), FDA may refrain from making a formal determination regarding eligibility for 180-
1033  day exclusivity.   
1034   
1035  It also is possible that an ANDA applicant could be informed upon approval that it is a first 
1036  applicant eligible for 180-day exclusivity, but later forfeit exclusivity under section 505(j)(5)(D) 
1037  of the FD&C Act.   
1038   
1039  Q45.  How can the public know if a paragraph IV certification has been submitted with 
1040  respect to a particular RLD? 
1041   
1042  FDA maintains on its website a list of drug products for which an ANDA has been received by 
1043  the Agency containing a paragraph IV certification.  The webpage is titled Paragraph IV Patent 
1044  Certifications.81  This list includes the drug product for which a paragraph IV certification has 
1045  been submitted, the dosage form, strength(s), RLD name, and date on which the first 
1046  substantially complete ANDA was submitted to FDA or, when applicable, the date of the first 
1047  paragraph IV certification.  FDA will not disclose the identity of the applicants of those ANDAs, 
1048  nor will FDA indicate the number of such ANDAs submitted on that date.  The information is 
1049  updated twice a month and is as current as the last update.  Although FDA makes every effort to 
1050  ensure the accuracy of the information provided in this list, this information should be used for 
1051  reference only.  Any discrepancies, disparities, or other questions about this information should 
1052  be discussed with the Office of Generic Drugs Division of Filing Review before making any 
1053  decisions based on the information. 
                                                 
81 This FDA webpage is available at 
http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/a
bbreviatednewdrugapplicationandagenerics/ucm047676.htm.   
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