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 Industry1 1

2

3 180-Day Exclusivity When Multiple ANDAs are 

4 Submitted on the Same Day

5

6

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.
Contains Nonbinding Recommendations

2

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 applicant’s drug or a court decision that holds that the patent that is the subject of the
Contains Nonbinding Recommendations

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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

is eligible for 180-day generic drug exclusivity.2 As noted in a 1999 citizen petition response,3 101

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

the number of times that 180-day exclusivity was granted.4 108 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.
Contains Nonbinding Recommendations

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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

and staff.5 163

 

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. 
Contains Nonbinding Recommendations

5

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
Contains Nonbinding Recommendations

6

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 FDA’s 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