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`Case 1:18—cv—00303-RGA Document 64-2 Filed 11/14/18 Page 1 of 31 PageID #: 1465
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`EXHIBIT B
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`EXHIBIT B
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`Case 1:18-cv-00303-RGA Document 64-2 Filed 11/14/18 Page 2 of 31 PageID #: 1466
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`Guidance for Industry
`180-Day Exclusivity:
`Questions and Answers
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`DRAFT GUIDANCE
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`This guidance document is being distributed for comment purposes only.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.
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`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)
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`January 2017
`Generic Drugs
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`

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`Guidance for Industry
`180-Day Exclusivity:
`Questions and Answers
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`
`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
`
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`Case 1:18-cv-00303-RGA Document 64-2 Filed 11/14/18 Page 4 of 31 PageID #: 1468
`Contains Nonbinding Recommendations
`Draft — Not for Implementation
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`Table of Contents
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`INTRODUCTION................................................................................................................. 1
`I.
`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
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`Draft — Not for Implementation
`Guidance for Industry
`180-Day Exclusivity: Questions and Answers1
`
`INTRODUCTION
`
`
`
`This draft guidance, when finalized, will represent the current thinking of the Food and Drug
`Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not
`binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the
`applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible
`for this guidance as listed on the title page.
`
`
`
`
`I.
`
`This guidance is intended to address questions that have been raised about the provisions of the
`Federal Food, Drug, and Cosmetic Act (FD&C Act) that relate to generic drug exclusivity, which
`commonly is known as 180-day exclusivity for generic drug products. As a general matter, the
`Food and Drug Administration (FDA or the Agency) has implemented these statutory provisions
`within the context of application-specific decisions. Some FDA decisions have been made
`publicly available (e.g., in FDA citizen petition responses and documents released in litigation).
`In addition, in certain circumstances where a novel issue of interpretation was raised by a
`particular factual scenario regarding forfeiture of 180-day exclusivity, FDA has opened a public
`docket or otherwise sought comment from affected parties in advance of taking an action. Also,
`in certain instances, applicants have submitted correspondence to their abbreviated new drug
`applications (ANDAs) regarding 180-day exclusivity, which FDA has considered in making
`decisions. FDA believes that a guidance for industry that provides answers to commonly asked
`questions about 180-day exclusivity would enhance transparency and facilitate the development,
`approval, and timely marketing of generic drug products. FDA intends to update this guidance
`to include additional questions and answers (Q&As) as appropriate.
`
`In general, FDA’s guidance documents 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.
`
`II.
`
`BACKGROUND
`
`The Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman
`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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`A.
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`ANDA Approval Pathway
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`2003, Congress enacted the Medicare Prescription Drug, Improvement, and Modernization Act
`of 2003 (MMA),4 which, among other things, substantially revised certain statutory provisions
`related to 180-day exclusivity. In this guidance, we will discuss 180-day exclusivity as it
`pertains to ANDAs subject to the MMA statutory provisions. This guidance does not discuss
`180-day exclusivity as it pertains to ANDAs subject to the pre-MMA statutory provisions. In
`Section III.A, we describe how to determine which statutory scheme applies to a particular
`ANDA.
`
`
`
`The process for obtaining approval to market an innovator drug approved under a new drug
`application (NDA) differs from that for obtaining approval to market a generic drug under an
`ANDA. A sponsor of an innovator drug must submit an NDA, which must contain, among other
`things, a demonstration of the safety and effectiveness of the drug for the conditions of use for
`which approval is sought.5 In its application, an NDA applicant must submit information for
`each patent that claims the drug or method of using the drug and for which a claim of patent
`infringement could reasonably be asserted against a person engaged in the unlicensed
`manufacture, use, or sale of the drug product.6 Upon approval of an NDA, FDA publishes this
`patent information in its publication Approved Drug Products with Therapeutic Equivalence
`Evaluations, known as the Orange Book.7
`
`To obtain approval of a generic drug, an ANDA applicant is not required to provide independent
`evidence of the safety and effectiveness of the proposed generic drug. Instead, the applicant
`relies on FDA’s previous finding that the reference listed drug (RLD)8 relied upon by the ANDA
`applicant is safe and effective. The ANDA applicant must identify the RLD on which it seeks to
`rely and, among other things, demonstrate, with limited exceptions, that the proposed generic
`drug has the same active ingredient(s), route of administration, dosage form, and strength as the
`RLD.9 A generic drug also must have the same conditions of use and the same labeling as the
`RLD (except for certain permissible labeling differences),10 and the applicant must demonstrate
`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).
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`B.
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`Patent Certification and 180-day Exclusivity
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`The timing of ANDA approval depends on, among other things, the patent and exclusivity
`protections for the RLD. An applicant must provide in its ANDA additional information related
`to any patents for the RLD. In particular, the ANDA applicant generally must submit to FDA
`one of four specified certifications regarding the patents for the RLD under section
`505(j)(2)(A)(vii) of the FD&C Act.
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`If the Orange Book does not list a patent for the RLD, the ANDA applicant must certify:
`
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`1. That such patent information has not been submitted by the NDA holder for listing in the
`Orange Book (a paragraph I certification).12
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`With respect to each patent listed in the Orange Book for the RLD, the applicant’s patent
`certification must state one of the following:
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`2. That such patent has expired (a paragraph II certification)
`3. The date on which such patent will expire (a paragraph III certification)
`4. That such patent is invalid, unenforceable, or will not be infringed by the manufacture,
`use, or sale of the new drug for which the application is submitted (a paragraph IV
`certification).13
`
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`If an applicant submits a paragraph I or II certification, the patent in question will not delay
`ANDA approval. If an applicant submits a paragraph III certification, the applicant agrees to
`wait until the relevant patent has expired before seeking final approval of its ANDA. If,
`however, an applicant wishes to seek approval of its ANDA before a listed patent has expired by
`challenging the validity of a patent, claiming that a patent would not be infringed by the product
`proposed in the ANDA, or claiming a patent is unenforceable, the applicant must submit a
`paragraph IV certification to FDA.
`
`The FD&C Act describes only one circumstance in which an ANDA applicant need not certify to
`a listed patent. Specifically, when a patent is listed only for a method of use, an ANDA
`applicant seeking to omit that approved method of use from the generic drug’s labeling can
`submit a section viii statement, acknowledging that a given method-of-use patent has been listed,
`but stating that the patent at issue does not claim a use for which the applicant seeks approval.14
`
`An applicant submitting a paragraph IV certification to a listed patent must provide the NDA
`holder and each patent owner notice of its paragraph IV certification, including a description of
`the legal and factual basis for the ANDA applicant’s 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).
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`unenforceable, or will not be infringed.15 If a patent is listed at the time an ANDA is submitted
`and, in response to notice of a paragraph IV certification, the NDA holder or patent owner
`initiates a patent infringement action against the ANDA applicant within 45 days of receiving the
`required notice, approval of the ANDA generally will be stayed for 30 months from the later of
`the date of receipt of the notice by any owner of the patent or the NDA holder or such shorter or
`longer time as the court might order.16 If a patent is listed in the Orange Book after an ANDA is
`submitted but before it is approved, the applicant for the pending ANDA generally must amend
`its application and provide an appropriate patent certification or statement to the newly listed
`patent; however, no 30-month stay will be available in this circumstance.17
`
`The statute provides an incentive and a reward to generic drug applicants that expose themselves
`to the risk of patent litigation. It does so by granting a 180-day period of exclusivity vis-à-vis
`certain other ANDA applicants to the applicant that is first to file a substantially complete
`ANDA containing a paragraph IV certification to a listed patent. If only one such ANDA is filed
`on the first day, there is only one first applicant; if two or more such ANDAs are filed on the
`first day, the ANDA applicants share first-applicant status.18 If an ANDA contains a paragraph
`IV certification for a relevant patent and the ANDA is not that of a first applicant, the ANDA
`applicant is regarded as a subsequent applicant.19
`
`If an ANDA meets the substantive requirements for approval, but cannot be finally approved due
`to unexpired patents or exclusivities, FDA will tentatively approve the ANDA. Tentative
`approval “means notification to an applicant by [FDA] that an [ANDA] meets the requirements
`of [section 505(j)(2)(A) of the FD&C Act] but cannot receive effective approval because the
`application does not meet the requirements of this subparagraph, there is a period of exclusivity
`for the listed drug under subparagraph (F) or section 505A, or there is a 7-year period of
`exclusivity for the listed drug under section 527.”20
`
`The FD&C Act describes a number of conditions under which an ANDA applicant may forfeit
`eligibility for 180-day exclusivity. These forfeiture events can be generally described as: (1)
`failure to market; (2) withdrawal of application; (3) amendment of certification; (4) failure to
`obtain tentative approval; (5) entry into agreement with another applicant, the listed drug
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`15 Section 505(j)(2)(B) of the FD&C Act.
`16 Section 505(j)(5)(B)(iii) of the FD&C Act and 21 CFR 314.107(b)(3)(i).
`17 Id. See also 21 CFR 314.94(a)(12)(vi).
`18 As described in Question 2, an applicant that submitted a substantially complete ANDA without a paragraph IV
`certification may become eligible for 180-day exclusivity by amending its application to contain a paragraph IV
`certification to a listed patent on the first day that an ANDA or amendment containing a paragraph IV certification is
`submitted for that RLD.
`19 See section 505(j)(5)(B)(iv)(I), (II)(aa) and 505(j)(5)(D)(iii) of the FD&C Act. See also 21 CFR 314.107(c)(1);
`Abbreviated New Drug Applications and 505(b)(2) Applications; Final Rule, 81 FR 69580, 69627-69628 (Oct. 6,
`2016).
`20 Section 505(j)(5)(B)(iv)(II)(dd)(AA) of the FD&C Act. See also 21 CFR 314.3(b) (defining tentative approval to
`also include, among other things, notification that an ANDA otherwise meets the requirements for approval under
`the FD&C Act, but cannot be approved because there is a period of exclusivity for the listed drug under section
`505E of the FD&C Act, or because a court order pursuant to 35 U.S.C. 271(e)(4)(A) orders that the ANDA may be
`approved no earlier than the date specified) and 21 CFR 314.105.
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`application holder, or a patent owner; and (6) expiration of all patents.21 Under these provisions,
`if certain events occur, an applicant eligible for 180-day exclusivity at the time its ANDA was
`submitted (first applicant) may forfeit eligibility for 180-day exclusivity. If all first applicants
`forfeit their eligibility for 180-day exclusivity, no applicant will be eligible for 180-day
`exclusivity, and FDA may approve subsequent applicants’ ANDAs, subject to the approval
`requirements of the FD&C Act.
`
`FDA has received a number of questions about 180-day exclusivity and has identified the
`following commonly asked questions for inclusion in this guidance. FDA expects the following
`information to enhance transparency and facilitate the development, approval, and timely
`marketing of generic drugs. FDA intends to update this guidance to include additional Q&As as
`appropriate.
`
`III. QUESTIONS AND ANSWERS
`
`
`A.
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`Applicable Statutory Scheme
`
`
`Q1. How does FDA determine whether the pre-MMA or MMA provisions of the FD&C
`Act apply to a particular ANDA?
`
`Section 1102(b)(1) of the MMA provides that the MMA 180-day exclusivity provisions are
`effective only with respect to an ANDA filed after the date of enactment (i.e., December 8, 2003)
`for a listed drug for which no paragraph IV certification was made before that date.22 The
`following list illustrates how FDA has applied this effective date provision in particular
`situations:
`
`
`•
`
`If all ANDAs referencing a particular RLD are submitted to FDA after December 8, 2003
`(and thus no paragraph IV certification could have been submitted before December 8,
`2003), the MMA 180-day exclusivity provisions apply to all of the ANDAs.
`If at least one ANDA with a paragraph IV certification to a listed patent for the RLD was
`submitted before December 8, 2003, all ANDAs referencing that RLD (including
`ANDAs submitted after December 8, 2003) are governed by the pre-MMA statutory
`provisions.
`If one or more ANDAs referencing a particular RLD were submitted before December 8,
`2003, but the first paragraph IV certification was submitted after December 8, 2003, the
`pre-MMA provisions govern for any ANDA referencing that RLD (whether or not that
`particular ANDA was filed before or after December 8, 2003), because section
`1102(b)(1) of the MMA is based on the date of submission of the first application, not on
`the date of the first paragraph IV certification.
`FDA has concluded that the effective date provision imposes the same statutory scheme on all
`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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`B.
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`First Applicants
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`statutory schemes to a single group of applications with a common RLD could result in conflict
`between the MMA and pre-MMA provisions. The eligibility, triggering, and forfeiture features
`of the different 180-day exclusivity schemes could render one applicant ineligible for exclusivity
`while another applicant could retain its eligibility. To avoid these inequitable outcomes, all
`ANDAs submitted referencing the same RLD will be subject to one statutory scheme.
`
`
`
`Q2. How does an ANDA applicant qualify as a “first applicant”?
`
`A first applicant is an ANDA “applicant that, on the first day on which a substantially complete
`application containing a [paragraph IV] certification … is submitted for approval of a drug,
`submits a substantially complete application that contains and lawfully maintains a [paragraph
`IV] certification … for the drug.”23
`
`An applicant that previously submitted a substantially complete ANDA that did not contain a
`paragraph IV certification may become eligible for 180-day exclusivity by amending its ANDA
`to contain a paragraph IV certification to a listed patent for the RLD on the first day that an
`ANDA or amendment containing a paragraph IV certification is submitted.
`
`The listed patent or patents to which an ANDA applicant submitted a paragraph IV certification
`that gives rise to the eligibility for 180-day exclusivity is referred to in this draft guidance as the
`qualifying patent(s).
`
`Q3. What constitutes a substantially complete application?
`
`A substantially complete application is an ANDA that on its face is sufficiently complete to
`permit a substantive review. Sufficiently complete means that the ANDA contains all the
`information required under section 505(j)(2)(A) of the FD&C Act and does not contain a
`deficiency described in 21 CFR 314.101(d) and (e).24 FDA indicates its determination that an
`ANDA is substantially complete when the Agency receives the ANDA for review under 21 CFR
`314.101. If FDA determines, after an initial evaluation, that an ANDA was substantially
`complete as of the date it was submitted to FDA, FDA will consider the ANDA to have been
`received as of the date of submission.25
`
`Q4. Does an ANDA applicant have to be the first to submit a paragraph IV certification
`to all of the RLD’s listed patents to be a first applicant?
`
`No. The statute requires “a” paragraph IV certification;26 it does not require a first applicant to
`be the first to submit a paragraph IV certification to more than a single patent (or all of the
`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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`6
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`There can be multiple patents that could qualify a single ANDA applicant as a first applicant, so
`long as they are certified to on that same first day that the first paragraph IV certification in an
`ANDA for that RLD is submitted. As a result, each qualifying patent separately can affect
`exclusivity. For example, if an ANDA applicant submitted paragraph IV certifications to two
`separate patents on the same first day and the first patent expires prior to triggering of 180-day
`exclusivity, the paragraph IV certification to the second patent can remain a basis for first-
`applicant status and for 180-day exclusivity.
`
`Q5. Can an ANDA applicant qualify as a first applicant when it includes both a
`paragraph IV certification and a section viii statement to a single listed patent?
`
`Yes. FDA has determined that when both drug product or drug substance claims and method-of-
`use claims are contained within the same patent, an applicant may file a paragraph IV
`certification with respect to the drug product or drug substance patent claim(s) and a section viii
`statement with respect to the method-of-use claim(s) in the patent. This type of certification is
`commonly referred to as a split certification. This approach preserves the NDA holder’s
`statutory right to assert its patent rights regarding the drug substance or drug product claims
`before ANDA approval while permitting the ANDA applicant to exercise its statutory right to
`avoid infringing a method-of-use claim by seeking approval for fewer than all of the approved
`conditions of use for the RLD. Consistent with this principle, the paragraph IV certification in a
`split certification can qualify an applicant for first applicant eligibility.
`
`Q6. Can an ANDA applicant be a first applicant if the applicant includes a paragraph
`III certification to a patent that expires after the patent to which a paragraph IV
`certification was submitted?
`
`Yes. The statutory definition of “first applicant” requires “a” paragraph IV certification. The
`statute does not require that the paragraph IV certification be to the latest expiring patent. For
`example, a first applicant could have a paragraph IV certification to a patent expiring on January
`1, 2020 (the only qualifying patent) and a paragraph III certification to a patent expiring on June
`1, 2030.
`
`Q7. Could the timing of sending notice of paragraph IV certification affect first
`applicant status?
`
`Yes. For original ANDAs, notice of paragraph IV certification must be provided on or after the
`date on which the applicant receives a paragraph IV acknowledgment letter from FDA, but not
`later than 20 days after the date of the postmark on the paragraph IV acknowledgment letter.27
`The paragraph IV acknowledgment letter is a written, postmarked communication from FDA to
`an applicant stating that the Agency has determined that an ANDA containing a paragraph IV
`certification is sufficiently complete to permit a substantive review and has been received for
`
`
`27 21 CFR 314.95(b)(1).
`
`
`
`7
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`
`Case 1:18-cv-00303-RGA Document 64-2 Filed 11/14/18 Page 12 of 31 PageID #: 1476
`Contains Nonbinding Recommendations
`Draft — Not for Implementation
`review.28 Any notice sent before the ANDA applicant’s receipt of a paragraph IV
`acknowledgment letter is invalid.29
`
`For amendments containing a paragraph IV certification submitted before the ANDA has been
`received for review (i.e., before receipt of a paragraph IV acknowledgment letter), the ANDA
`applicant must send notice according to the timeframe described above for original ANDAs. If
`an ANDA applicant’s notice of its paragraph IV certification is timely provided and the applicant
`has not submitted a previous paragraph IV certification, FDA will base its determination of
`whether the ANDA applicant is a first applicant on the date of submission of the amendment
`containing the paragraph IV certification.30
`
`For amendments submitted after the ANDA has been received for review (i.e., after receipt of an
`acknowledgment letter or a paragraph IV acknowledgment letter) and supplements, notice of
`paragraph IV certification must be provided at the same time that the amendment or supplement
`is submitted to FDA. If notice is not sent simultaneously with an amendment or supplement,
`FDA considers the paragraph IV certification not to be effective until notice is provided.31 For
`example, if an ANDA applicant submitted a supplement containing a paragraph IV certification,
`but notice of the paragraph IV certification was not provided until 30 days after the submission
`of the supplement, FDA would evaluate whether the applicant was a first applicant based on the
`date notice was provided, rather than the date of submission of the supplement. Thus, a delay in
`giving notice of certain amendments or supplements could mean a later date for the paragraph IV
`certification to become effective which could result in failure to obtain first applicant status (if
`another applicant submits a certification that becomes effective in the interim).
`
`Regardless of whether it is an original ANDA, an amendment, or a supplement, a paragraph IV
`certification must not be submitted earlier than the first working day after the day the patent is
`published in the Orange Book.32 Any notice sent before the first working day after the day the
`patent is published in the Orange Book is invalid.33
`
`Q8. What does it mean to “lawfully maintain” a paragraph IV certification?
`
`The definition of first applicant requires that the applicant “lawfully maintain[] a [paragraph IV]
`certification.”34 This requires an uninterrupted paragraph IV certification to the qualifying patent
`or patent claim. For example, an applicant has not lawfully maintained its paragraph IV
`certification if the applicant initially submits a paragraph IV certification to a patent or patent
`claim, and then later amends its ANDA to include a paragraph III certification or a section viii
`statement to the qualifying patent or patent claim, and then amends its ANDA again to include a
`paragraph IV certification to the same patent or patent claim. However, if the applicant initially
`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