180-Day Exclusivity When Multiple ANDAs Are Submitted on the Same Day

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

Guidance for Industry
180-Day Exclusivity 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
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Guidance for Industry1
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180-Day Exclusivity When Multiple ANDAs are	3
Submitted on the Same Day	4
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This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.
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I. 	INTRODUCTION
This guidance is intended to provide information on how the Food and Drug Administration
(FDA) intends to determine eligibility for 180-day generic drug exclusivity when, on the same
day, more than one applicant submits an abbreviated new drug application (ANDA) for the same
drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act (Act) containing a
paragraph IV certification to a listed patent, and no paragraph IV certification to the patent was
submitted on any previous day. To date, FDA's exclusivity decisions have involved applications
or amendments submitted on different days. This guidance explains why and how the Agency
intends to apply a multiple first applicant approach.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
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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
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II. 	BACKGROUND	36
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The Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. No. 98-417) (the
Hatch-Waxman Amendments) amended the Federal Food, Drug, and Cosmetic Act (the Act).
The Hatch-Waxman Amendments created section 505(j) of the Act (21 U.S.C. 355(j)). Section
505(j) established the ANDA approval process, which allows lower-priced generic versions of
previously approved innovator drugs to be approved and brought on the market.
An innovator drug applicant must include in its new drug application (NDA) information about
any patents that claim the drug product that is the subject of the NDA, or the use of such drug
product (21 U.S.C. 355(b)(1) and (c)(2)). The FDA publishes this patent information upon
approval of the NDA or a supplemental NDA in Approved Drug Products with Therapeutic
Equivalence Evaluations, which is generally known as the Orange Book.
An ANDA applicant must include in its ANDA a patent certification as described in section
505(j)(2)(A)(vii) of the Act. The certification must make one of the following statements: (1)
such patent information has not been filed; (2) such patent has expired; (3) the date on which
such patent expires; or (4) such patent is invalid or will not be infringed by the manufacture, use,
or sale of the drug product for which the ANDA is submitted. The fourth certification is known
as a paragraph IV certification. The ANDA applicant must provide appropriate notice of a
paragraph IV certification to each owner of the patent that is the subject of the certification and
to the holder of the approved NDA to which the ANDA refers (21 U.S.C. 505(j)(2)(B)(i), 21
CFR 314.95). Section 505(j)(5)(B)(iv) of the Act established an incentive for generic
manufacturers to file paragraph IV certifications and to challenge listed patents as invalid, or not
infringed, by providing for a 180-day period of marketing exclusivity:
If the [ANDA] contains a [paragraph IV certification] and is for a drug for which a	62
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previous application has been submitted under this subsection continuing [sic]
such a certification, the application shall be made effective not earlier than one
hundred and eighty days after—
(I)
(II)
the date the Secretary receives notice from the applicant under the
previous [ANDA] of the first commercial marketing of the drug
under the previous [ANDA], or
the date of a decision of a court in [a patent infringement
action] holding the patent which is the subject of the
certification to be invalid or not infringed, [the font size of
this paragraph needs to be 11]
whichever is earlier.
This means that, in certain circumstances, an applicant who submits the ANDA containing the
first paragraph IV certification to a patent is protected from competition from other generic
versions of the same drug product for 180 days after the earliest of either the initial marketing of
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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paragraph IV certification is invalid or not infringed. This marketing protection is commonly	82
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known as 180-day exclusivity.
III. 	DISCUSSION
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The 180-day period of generic drug exclusivity provides a very strong financial incentive for an	88
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ANDA applicant to challenge a patent that it believes it does not infringe or that it believes is
invalid or unenforceable. The Congressional Budget Office (CBO) issued a report in July 1998
entitled How Increased Competition from Generic Drugs has Affected Prices in the
Pharmaceutical Industry. This report indicated that the price of a generic drug decreases with
the entry of multiple manufacturers selling generic duplicates of a given innovator drug (see
CBO report page 33). With less competition, an ANDA holder is able to derive higher profits.
Thus, the opportunity to be the sole competitor to the innovator for up to 6 months is
aggressively pursued.
Since the decisions in Mova Pharmaceuticals, Inc. v. Shalala, 140 F.3d 1060 (D.C.Cir. 1998)
and Granutec, Inc. v. Shalala, 46 U.S.P.Q.2d 1398 (4th Cir. 1998), the first applicant who
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
many of the current regulations were adopted prior to the Mova decision, when the Agency
interpreted the statute to require that an ANDA applicant had to be sued and win its patent
litigation to qualify for exclusivity. FDA's pre-Mova interpretation limited the number of times
180-day exclusivity was granted because an ANDA applicant had to be first to challenge a patent
and win the patent litigation to be eligible for 180-day exclusivity. The chance of having
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 By contrast, after the Mova decision,
it is now easier to qualify for 180-day exclusivity. As a result, FDA has had to address a number
of new issues, including eligibility for exclusivity when multiple paragraph IV certifications are
filed on the same day.
Congress did not address, in the 180-day exclusivity provisions of the Act, the possibility that
multiple applicants would submit patent challenges to FDA on the same day, when no applicant
had submitted a challenge to the patent on a previous day. Similarly, FDA regulations now in
effect do not address this specific situation. In August 1999, FDA proposed a multiple first	116
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applicant approach in a proposed rule addressing 180-day generic drug exclusivity (64 FR
42873; August 6, 1999). FDA received comments both for and against this approach (see
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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merits of the multiple first applicant approach (67 FR 66593; November 1, 2002). 	When the	120
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proposed rule was withdrawn, the Agency noted that it would continue to regulate directly from
the statute and any applicable regulations, and make decisions on an issue-by-issue basis. The
Agency continues to believe that the approach described in the proposed rule is a reasonable and
appropriate interpretation of the statute. Two citizen petitions have specifically asked the
Agency to follow the approach described in the proposed rule when addressing 180-day
exclusivity in cases where there are multiple ANDAs containing challenges to the same patent
submitted on the same day (see Dockets 00P-1445 and 03P-0217).
Same day patent challenges generally occur when the expiration of 4 years of a 5-year
exclusivity period under section 505(j)(5)(D)(ii) permits submission of ANDAs containing a
paragraph IV certification as of a specific date, and multiple applicants vie to be first to make
such a submission. Multiple submissions on the same day may also occur when a new patent is
issued by the Patent and Trademark Office and submitted to FDA by the NDA sponsor after
ANDAs have been submitted. Because new patents must be submitted to FDA within 30 days of
issuance, ANDA applicants position themselves to be the first to submit a paragraph IV
certification as soon as the patent is submitted to FDA – often exactly 30 days after patent
issuance.
Recently, there have been a number of cases in which multiple ANDA applicants or their
representatives have sought to be the first to submit a patent challenge by lining up outside, and
literally camping out adjacent to, an FDA building for periods ranging from 1 day to more than 3
weeks. Concerns about liability, security, and safety led the property owners to prohibit lines of
applicants before the date submissions may be made. This has lent an urgency to the question of
how the Agency deals with multiple ANDA applicants submitting paragraph IV certifications on
the same day. 	There are other periods of exclusivity expiring soon, and FDA believes it is
possible there will be multiple ANDA submissions referencing the same listed drug. Because of
the seriousness of these issues, it has been necessary to promptly provide information to the
industry on how patent challenges may be made to FDA and how FDA will apply the 180-day
exclusivity provisions of the statute to these submission.	149
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FDA intends to apply a multiple first applicant approach to eligibility for 180-day exclusivity by
considering all substantially complete ANDAs, amendments, and supplements containing a
paragraph IV certification to a listed patent that are submitted to the OGD document room on the
same day as being first applicants, when no paragraph IV certification to the patent has been
submitted on any previous day, as long as the applications comply with the applicable
requirements for submission. FDA considers this approach to be an appropriate interpretation of
the statutory language and consistent with the goals of the Hatch-Waxman Amendments. This
approach will provide all applicants submitting patent challenges on the same day an opportunity
to share in exclusivity; it permits submission by U.S. mail or courier or delivery service; it
permits, but does not require, submission in person; it avoids the random aspect of a lottery or
mail room date stamp approach; it will prevent disputes over who's first, which rely on video and
other evidence; and it will preserve the safety and security of the applicants and FDA property
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.

Contains Nonbinding Recommendations
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IV. 	HOW MULTIPLE APPLICANT EXCLUSIVITY WORKS	166
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Under the approach described in this guidance, FDA intends to treat all ANDAs containing a
paragraph IV certification to a listed patent that are submitted on the same day as being
submitted at the same time for purposes of 180-day exclusivity when no ANDA for the same
drug product containing a paragraph IV certification to the same patent has been submitted on a
previous day. Thus, none of those same-day submissions would be considered "previous[ly] . . .
submitted" to another patent challenge submitted on that same day for purposes of section
505(j)(5)(B)(iv), and all applicants who fulfill the requirements for submission would be
considered first applicants. The Agency intends to approve a first applicant's ANDA whenever
it is ready for approval. Whether and when the Agency will be able to approve a first applicant's
ANDA will depend upon a number of factors, including, for example, the status of its scientific
submissions to the Agency. Exclusivity begins to run, independent of the approval, with the
commercial marketing of that drug product or with a court decision on the patent, whichever
comes first. Exclusivity will be triggered for all of the first applicants for a specific listed patent
by the earlier of commercial marketing by one of the first applicants or by a court decision
(regarding the patent as to which the applicant is a first applicant) finding the patent invalid,
unenforceable, or not infringed. The commercial marketing trigger will begin exclusivity as to
all of the listed patents; a court decision will only begin the running of exclusivity as to the
patents addressed in the decision.
During the exclusivity period, FDA may approve any other first applicant's ANDA, but no other
ANDAs. Any first applicant whose ANDA is approved after the exclusivity has been triggered
will share in the remaining period of exclusivity. Once the 180-day exclusivity period has run,
FDA may approve all subsequent ANDAs.
Obviously, this approach may deprive any one applicant of the chance to be the sole competitor
to the NDA holder. But exclusivity is already structured in such a way that eligibility for
exclusivity does not guarantee 180 days as the sole marketed generic drug (i.e., the court
decision trigger could start exclusivity before an ANDA is approved, or uncertainty over the
patent could result in no marketing of an approved product until an affirmation in the Federal
Circuit of a district court win). A multiple first applicant approach to 180-day exclusivity will
limit the number of ANDAs approved during the exclusivity period to the number of first
applicants. Moreover, making multiple applicants eligible for exclusivity may give each first
applicant some part of the benefit from the early challenge to the listed patent.
The approach to 180-day exclusivity described in this guidance will apply only in cases in which
multiple ANDA applicants submit paragraph IV certifications challenging the same listed patent
or patents on the same first day. The Agency recognizes the highly competitive nature of the
generic drug approval process and the possibility of substantial profits for the recipient of 180-
day exclusivity. There is no public health reason to encourage and reward competition over
being the first to submit a paragraph IV certification within minutes or seconds of another such
applicant. The Agency believes that, where there are multiple filings on the same first day, the

Contains Nonbinding Recommendations
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multiple first applicant approach is consistent with language of section 505(j)(5)(B)(iv) and with	209
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the intent of both the 180-day exclusivity provision and the Hatch-Waxman Amendments.
V. 	IMPLEMENTATION
This guidance is being issued as a level 1 guidance for immediate implementation, consistent with
FDA’s good guidance practices regulation (21 CFR 10.115). The Agency believes that given the
need for public guidance on this pressing issue and existing liability, safety, and security concerns,
public comment is neither feasible nor appropriate before implementing this guidance. FDA
intends to apply the approach described in this guidance to all 180-day exclusivity determinations
made by FDA on or after the date of publication of the notice announcing the availability of this
guidance involving situations in which the first paragraph IV certifications to a specific patent are
submitted on the same day (including patent certifications that were submitted prior to the date of
the notice where the exclusivity determination has not yet been made). The approach described in
this guidance will remain in effect until superseded.