Guidance for Industry
180-Day Exclusivity When
Multiple ANDAs Are
Submitted on the Same Day
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
July 2003
OGD  Guidance for Industry
180-Day Exclusivity When
Multiple ANDAs Are
Submitted on the Same Day
Additional copies are available from:
Office of Training and Communication
Division of Drug Information, HFD-240
Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane
Rockville, MD  20857
(Tel) 301-827-4573
 http://www.fda.gov/cder/guidance/index.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
July 2003
OGD Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. INTRODUCTION.................................................................................................................1
II. BACKGROUND...................................................................................................................2
III. DISCUSSION........................................................................................................................3
IV. HOW MULTIPLE APPLICANT EXCLUSIVITY WORKS...........................................5
V. IMPLEMENTATION..........................................................................................................6 Contains Nonbinding Recommendations
1
Guidance for Industry
1
2
180-Day Exclusivity When Multiple ANDAs are 
3
Submitted on the Same Day
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7
8 This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It
9 does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
10 You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
11 and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for
12 implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate
13 number listed on the title page of this guidance. 
14
15
16
17
18 I. INTRODUCTION
19
20 This guidance is intended to provide information on how the Food and Drug Administration
21 (FDA) intends to determine eligibility for 180-day generic drug exclusivity when, on the same
22 day, more than one applicant submits an abbreviated new drug application (ANDA) for the same
23 drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act (Act) containing a
24 paragraph IV certification to a listed patent, and no paragraph IV certification to the patent was
25 submitted on any previous day.  To date, FDA's exclusivity decisions have involved applications
26 or amendments submitted on different days.  This guidance explains why and how the Agency
27 intends to apply a multiple first applicant approach. 
28
29 FDA's guidance documents, including this guidance, do not establish legally enforceable
30 responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should
31 be viewed only as recommendations, unless specific regulatory or statutory requirements are
32 cited.  The use of the word should in Agency guidances means that something is suggested or
33 recommended, but not required. 
34
35
                                                
1 This guidance has been prepared by the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and
Research (CDER) in cooperation with the Office of Regulatory Policy  (ORP) and the Office of the Chief Counsel
(OCC) at the Food and Drug Administration.
1 Contains Nonbinding Recommendations
36 II. BACKGROUND
37
38 The Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. No. 98-417) (the
39 Hatch-Waxman Amendments) amended the Federal Food, Drug, and Cosmetic Act (the Act).
40 The Hatch-Waxman Amendments created section 505(j) of the Act (21 U.S.C. 355(j)).  Section
41 505(j) established the ANDA approval process, which allows lower-priced generic versions of
42 previously approved innovator drugs to be approved and brought on the market.
43
44 An innovator drug applicant must include in its new drug application (NDA) information about
45 any patents that claim the drug product that is the subject of the NDA, or the use of such drug
46 product (21 U.S.C. 355(b)(1) and (c)(2)).  The FDA publishes this patent information upon
47 approval of the NDA or a supplemental NDA in Approved Drug Products with Therapeutic
48 Equivalence Evaluations, which is generally known as the Orange Book. 
49
50 An ANDA applicant must include in its ANDA a patent certification as described in section
51 505(j)(2)(A)(vii) of the Act.  The certification must make one of the following statements: (1)
52 such patent information has not been filed; (2) such patent has expired; (3) the date on which
53 such patent expires; or (4) such patent is invalid or will not be infringed by the manufacture, use,
54 or sale of the drug product for which the ANDA is submitted.  The fourth certification is known
55 as a paragraph IV certification.  The ANDA applicant must provide appropriate notice of a
56 paragraph IV certification to each owner of the patent that is the subject of the certification and
57 to the holder of the approved NDA to which the ANDA refers (21 U.S.C. 505(j)(2)(B)(i), 21
58 CFR 314.95).  Section 505(j)(5)(B)(iv) of the Act established an incentive for generic
59 manufacturers to file paragraph IV certifications and to challenge listed patents as invalid, or not
60 infringed, by providing for a 180-day period of marketing exclusivity: 
61
62 If the [ANDA] contains a [paragraph IV certification] and is for a drug for which a
63 previous application has been submitted under this subsection continuing [sic]
64 such a certification, the application shall be made effective not earlier than one
65 hundred and eighty days after
66
67 (I)  the date the Secretary receives notice from the applicant under the
68 previous [ANDA] of the first commercial marketing of the drug
69 under the previous [ANDA], or
70
71 (II) the date of a decision of a court in [a patent infringement
72 action] holding the patent which is the subject of the
73 certification to be invalid or not infringed,  [the font size of
74 this paragraph needs to be 11]
75
76 whichever is earlier.
77
78 This means that, in certain circumstances, an applicant who submits the ANDA containing the
79 first paragraph IV certification to a patent is protected from competition from other generic
80 versions of the same drug product for 180 days after the earliest of either the initial marketing of
81 the first applicants drug or a court decision that holds that the patent that is the subject of the
2 Contains Nonbinding Recommendations
82 paragraph IV certification is invalid or not infringed.  This marketing protection is commonly
83 known as 180-day exclusivity. 
84
85
86 III. DISCUSSION
87
88 The 180-day period of generic drug exclusivity provides a very strong financial incentive for an
89 ANDA applicant to challenge a patent that it believes it does not infringe or that it believes is
90 invalid or unenforceable.  The Congressional Budget Office (CBO) issued a report in July 1998
91 entitled How Increased Competition from Generic Drugs has Affected Prices in the
92 Pharmaceutical Industry.  This report indicated that the price of a generic drug decreases with
93 the entry of multiple manufacturers selling generic duplicates of a given innovator drug (see
94 CBO report page 33).  With less competition, an ANDA holder is able to derive higher profits.
95 Thus, the opportunity to be the sole competitor to the innovator for up to 6 months is
96 aggressively pursued. 
97
98 Since the decisions in Mova Pharmaceuticals, Inc. v. Shalala, 140 F.3d 1060 (D.C.Cir. 1998)
99 and Granutec, Inc. v. Shalala, 46 U.S.P.Q.2d 1398 (4th Cir. 1998), the first applicant who
100 submits a substantially complete ANDA containing a paragraph IV certification to a listed patent
101 is eligible for 180-day generic drug exclusivity.2  As noted in a 1999 citizen petition response,3
102 many of the current regulations were adopted prior to the Mova decision, when the Agency
103 interpreted the statute to require that an ANDA applicant had to be sued and win its patent
104 litigation to qualify for exclusivity.  FDA's pre-Mova interpretation limited the number of times
105 180-day exclusivity was granted because an ANDA applicant had to be first to challenge a patent
106 and win the patent litigation to be eligible for 180-day exclusivity.  The chance of having
107 multiple ANDA applicants qualify for 180-day exclusivity was extremely low as evidenced by
108 the number of times that 180-day exclusivity was granted.4  By contrast, after the Mova decision,
109 it is now easier to qualify for 180-day exclusivity.  As a result, FDA has had to address a number
110 of new issues, including eligibility for exclusivity when multiple paragraph IV certifications are
111 filed on the same day.
112
113 Congress did not address, in the 180-day exclusivity provisions of the Act, the possibility that
114 multiple applicants would submit patent challenges to FDA on the same day, when no applicant
115 had submitted a challenge to the patent on a previous day.  Similarly, FDA regulations now in
116 effect do not address this specific situation.  In August 1999, FDA proposed a multiple first
117 applicant approach in a proposed rule addressing 180-day generic drug exclusivity (64 FR
118 42873; August 6, 1999).  FDA received comments both for and against this approach (see
119 Docket  85N-0214).  The proposed rule was withdrawn in 2002 for reasons unrelated to the
                                                
2 The regulatory history of this issue has been previously described in the June 1998 CDER guidance for industry
180-Day Generic Drug Exclusivity Under the Hatch-Waxman Amendments to the Federal Food, Drug, and
Cosmetic Act.
3 See response to 99P-1271/PSA1 and PSA2 issued August 2, 1999.
4 In the years from 1984 to 1998, only three ANDA applicants qualified for 180-day exclusivity.  Since the Mova
decision in 1999,  more than 60 ANDAs have received 180 days of exclusivity.
3 Contains Nonbinding Recommendations
120 merits of the multiple first applicant approach (67 FR 66593; November 1, 2002).   When the
121 proposed rule was withdrawn, the Agency noted that it would continue to regulate directly from
122 the statute and any applicable regulations, and make decisions on an issue-by-issue basis.  The
123 Agency continues to believe that the approach described in the proposed rule is a reasonable and
124 appropriate interpretation of the statute.  Two citizen petitions have specifically asked the
125 Agency to follow the approach described in the proposed rule when addressing 180-day
126 exclusivity in cases where there are multiple ANDAs containing challenges to the same patent
127 submitted on the same day (see Dockets 00P-1445 and 03P-0217).  
128
129 Same day patent challenges generally occur when the expiration of 4 years of a 5-year
130 exclusivity period under section 505(j)(5)(D)(ii) permits submission of ANDAs containing a
131 paragraph IV certification as of a specific date, and multiple applicants vie to be first to make
132 such a submission.  Multiple submissions on the same day may also occur when a new patent is
133 issued by the Patent and Trademark Office and submitted to FDA by the NDA sponsor after
134 ANDAs have been submitted.  Because new patents must be submitted to FDA within 30 days of
135 issuance, ANDA applicants position themselves to be the first to submit a paragraph IV
136 certification as soon as the patent is submitted to FDA  often exactly 30 days after patent
137 issuance. 
138
139 Recently, there have been a number of cases in which multiple ANDA applicants or their
140 representatives have sought to be the first to submit a patent challenge by lining up outside, and
141 literally camping out adjacent to, an FDA building for periods ranging from 1 day to more than 3
142 weeks.  Concerns about liability, security, and safety led the property owners to prohibit lines of
143 applicants before the date submissions may be made.  This has lent an urgency to the question of
144 how the Agency deals with multiple ANDA applicants submitting paragraph IV certifications on
145 the same day.   There are other periods of exclusivity expiring soon, and FDA believes it is
146 possible there will be multiple ANDA submissions referencing the same listed drug.  Because of
147 the seriousness of these issues, it has been necessary to promptly provide information to the
148 industry on how patent challenges may be made to FDA and how FDA will apply the 180-day
149 exclusivity provisions of the statute to these submission.
150
151 FDA intends to apply a multiple first applicant approach to eligibility for 180-day exclusivity by
152 considering all substantially complete ANDAs, amendments, and supplements containing a
153 paragraph IV certification to a listed patent that are submitted to the OGD document room on the
154 same day as being first applicants, when no paragraph IV certification to the patent has been
155 submitted on any previous day, as long as the applications comply with the applicable
156 requirements for submission.  FDA considers this approach to be an appropriate interpretation of
157 the statutory language and consistent with the goals of the Hatch-Waxman Amendments.  This
158 approach will provide all applicants submitting patent challenges on the same day an opportunity
159 to share in exclusivity; it permits submission by U.S. mail or courier or delivery service; it
160 permits, but does not require, submission in person; it avoids the random aspect of a lottery or
161 mail room date stamp approach; it will prevent disputes over who's first, which rely on video and
162 other evidence; and it will preserve the safety and security of the applicants and FDA property
163 and staff.5 
                                                
5   Consistent with FDA's current practice, submission by facsimile or email is not considered officially submitted
for purposes of determining the date of submission. 
4 Contains Nonbinding Recommendations
164
165
166 IV. HOW MULTIPLE APPLICANT EXCLUSIVITY WORKS
167
168 Under the approach described in this guidance, FDA intends to treat all ANDAs containing a
169 paragraph IV certification to a listed patent that are submitted on the same day as being
170 submitted at the same time for purposes of 180-day exclusivity when no ANDA for the same
171 drug product containing a paragraph IV certification to the same patent has been submitted on a
172 previous day.  Thus, none of those same-day submissions would be considered "previous[ly] . . .
173 submitted" to another patent challenge submitted on that same day for purposes of section
174 505(j)(5)(B)(iv), and all applicants who fulfill the requirements for submission would be
175 considered first applicants.  The Agency intends to approve a first applicant's ANDA whenever
176 it is ready for approval. Whether and when the Agency will be able to approve a first applicant's
177 ANDA will depend upon a number of factors, including, for example, the status of its scientific
178 submissions to the Agency.  Exclusivity begins to run, independent of the approval, with the
179 commercial marketing of that drug product or with a court decision on the patent, whichever
180 comes first.  Exclusivity will be triggered for all of the first applicants for a specific listed patent
181 by the earlier of commercial marketing by one of the first applicants or by a court decision
182 (regarding the patent as to which the applicant is a first applicant) finding the patent invalid,
183 unenforceable, or not infringed.  The commercial marketing trigger will begin exclusivity as to
184 all of the listed patents; a court decision will only begin the running of exclusivity as to the
185 patents addressed in the decision. 
186
187 During the exclusivity period, FDA may approve any other first applicant's ANDA, but no other
188 ANDAs.  Any first applicant whose ANDA is approved after the exclusivity has been triggered
189 will share in the remaining period of exclusivity.  Once the 180-day exclusivity period has run,
190 FDA may approve all subsequent ANDAs.
191
192 Obviously, this approach may deprive any one applicant of the chance to be the sole competitor
193 to the NDA holder.  But exclusivity is already structured in such a way that eligibility for
194 exclusivity does not guarantee 180 days as the sole marketed generic drug (i.e., the court
195 decision trigger could start exclusivity before an ANDA is approved, or uncertainty over the
196 patent could result in no marketing of an approved product until an affirmation in the Federal
197 Circuit of a district court win).  A multiple first applicant approach to 180-day exclusivity will
198 limit the number of ANDAs approved during the exclusivity period to the number of first
199 applicants.  Moreover, making multiple applicants eligible for exclusivity may give each first
200 applicant some part of the benefit from the early challenge to the listed patent.  
201
202 The approach to 180-day exclusivity described in this guidance will apply only in cases in which
203 multiple ANDA applicants submit paragraph IV certifications challenging the same listed patent
204 or patents on the same first day.  The Agency recognizes the highly competitive nature of the
205 generic drug approval process and the possibility of substantial profits for the recipient of 180-
206 day exclusivity.  There is no public health reason to encourage and reward competition over
207 being the first to submit a paragraph IV certification within minutes or seconds of another such
208 applicant.  The Agency believes that, where there are multiple filings on the same first day, the
5 Contains Nonbinding Recommendations
209 multiple first applicant approach is consistent with language of section 505(j)(5)(B)(iv) and with
210 the intent of both the 180-day exclusivity provision and the Hatch-Waxman Amendments. 
211
212
213 V. IMPLEMENTATION
214
215 This guidance is being issued as a level 1 guidance for immediate implementation, consistent with
216 FDAs good guidance practices regulation (21 CFR 10.115).  The Agency believes that given the
217 need for public guidance on this pressing issue and existing liability, safety, and security concerns,
218 public comment is neither feasible nor appropriate before implementing this guidance.  FDA
219 intends to apply the approach described in this guidance to all 180-day exclusivity determinations
220 made by FDA on or after the date of publication of the notice announcing the availability of this
221 guidance involving situations in which the first paragraph IV certifications to a specific patent are
222 submitted on the same day  (including patent certifications that were submitted prior to the date of
223 the notice where the exclusivity determination has not yet been made).  The approach described in
224 this guidance will remain in effect until superseded.
225
226
6