CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203214Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 203214
`
`SUPPL#
`
`'
`
`HFD # 570
`
`Trade Name
`
`Xeljanz
`
`Generic Name
`
`tofacitinib
`
`Applicant Name
`
`Pfizer, Inc
`
`Approval Date, If Known November 6, 2012
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`a)
`
`Is it a 505(b)(l), 505(b)(2) or efficacy supplement?
`
`YES E
`
`NO D
`
`If yes, what type? Specify 505(b)(l), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`0) Did it require the review of clinical data other than to support a safety claim or change in
`labeling related to safety? (If it required review only of bioavailability or bioequivalence
`data, answer "no."
`
`YES E
`
`NO I]
`
`If your answer is "no" because you believe the study is~a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`Reference ID: 3213344
`
`Page 1
`
`

`

`d) Did the applicant request exclusivity?
`
`YES E
`
`NO E]
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`5 years
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES D
`
`NO X]
`
`If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS'DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`YES D
`
`NO @
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`PART II
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`(Answer either #1 or #2 as appropriate)
`'
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen
`or coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate)
`has not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`YES [:1
`
`NO E
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`Reference ID: 3213344
`
`P
`
`age
`
`2
`
`

`

`NDA#
`
`NDA#
`
`NDA#
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing M _on_e of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA,
`is considered not previously
`
`approved.)
`
`YES
`
`D
`
`D
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`I
`
`NDA#
`
`NDA#
`
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval ofthe application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a)
`
`Reference ID: 3213344
`
`Page 3
`
`

`

`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`
`YES El
`
`NO D
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval“ if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`YES D
`
`NO [:1
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would not
`independently support approval of the application?
`
`YES El
`
`NO El
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`YES E]
`
`NO [:1
`
`If yes, explain:
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`Reference ID: 3213344
`
`Page 4
`
`

`

`If yes, explain:
`
`(0)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that I) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`YES I:I
`
`NO |:l
`
`YES l:l
`
`NO I:
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NBA in which each was relied upon:
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`'
`
`YES [:1
`
`NO D
`
`_
`
`YES 1:]
`
`NO E]
`
`Reference ID: 3213344
`
`Page 5
`
`

`

`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new" :
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(0): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`I!
`
`I NO D
`! Explain:
`
`-
`
`Investigation #1
`
`IND#
`
`YES D
`
`!l
`
`! NO [:1
`1 Explain:
`
`Investigation #2
`
`IND#
`
`YES D
`
`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant’s predecessor in
`interest provided substantial support for the study?
`Investigation #1
`
`lv
`
`Reference ID: 3213344
`
`P
`
`,
`
`age 5
`
`

`

`Investigation #2 '
`
`!
`
`YESI:I
`Explain:
`
`INoD
`! Explain:
`
`(0) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (notjust studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`
`YES D
`
`NO [I
`
`If yes, explain:
`
`
`
`Name of person completing form: Philantha Bowen, MPH, RN
`Title: Sr. Program Management Oflicer
`Date: 10/25/12
`
`Name of Office/Division Director signing form: Badrul A. Chowdhury, MD, PhD
`Title: Division Director
`Date: 10/26/12
`
`Form OGD-Ol 1347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference 1D: 3213344
`
`Page 7
`
`

`

`This is a representation of an electronic record that was signed_
`electronically and this page is the manifestation of the electronlc
`signature.
`
`‘PHILANTHA M BOWEN
`11/06/2012
`
`BADRUL A CHOWDHURY
`
`11/07/2012
`
`Reference ID: 3213344
`
`

`

`Module 1.3.3
`Debarment Certification
`
`DEBARMENT CERTIFICATION
`
`{FD&C Act 386(k)(1)]
`
`Pfizer hereby certifies that it did not and will not use in any capacity the services of any
`person debarred under Section 306 of the Federal Food, Drug, and Cosmetic Act in
`connection with this appiication.
`
`3 f
`
`i
`
`"a
`
`3
`
`W“are
`
`
`
`
`Signature of Company Repres ‘ tatlve
`
`"
`
`47
`
`
`
`090177e1825da8ae\Final\FinalOn:26-Sep-20'i
`
`Pfizer Confidential
`
`Page 1 of I
`
`

`

`
`
`
`
`
`
`
`
`
`
`Date:
`
`To:
`
`
`Company:
`
`Fax:
`
`Phone:
`
`
`From:
`
`
`
`
`
`Subject:
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Drug Evaluation II
`
`
`
`
`Memorandum of Facsimile Correspondence
`
`
`
`November 6, 2012
`
`Nickie Kilgore, DVM
`Director, Worldwide Regulatory Strategy
`
`Pfizer, Inc.
`
`860-686-7545
`
`860-441-5030
`
`Philantha Bowen, MPH, RN
`Senior Regulatory Management Officer
`Division of Pulmonary, Allergy, and Rheumatology Products
`
`NDA 203214 (Xeljanz) - Labeling Request # 5
`
` #
`
` of Pages including cover: 36
`
`
`THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO
`WHOM IT IS ADDRESSED AND MAY CONTAIN INFORMATION THAT IS
`PRIVILEGED, CONFIDENTIAL AND PROTECTED FROM DISCLOSURE
`UNDER APPLICABLE LAW.
`If you are not the addressee, you are hereby notified that any review, disclosure,
`dissemination, copying, or other action based on the content of this communication is not
`authorized. If you received this document in error, please immediately notify us by
`telephone at (301) 796-2300 and return it to us at FDA, 10903 New Hampshire Ave,
`Building 22, DPAP, Silver Spring, MD 20993.
`
`Thank you.
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3213051
`
`

`

`NDA 203214
`Tofacitinib Tablets
`Pfizer
`
`Dr. Kilgore:
`
`Your labeling submission dated November 5, 2012, to NDA 202314 is currently under
`review. The enclosed label contains FDA revisions that are highlighted for identification
`purposes only. The FDA-proposed insertions are underlined and deletions are in strike-
`out. Be advised that these comments are not all-inclusive and we may have additional
`recommendations as we continue our review of the label.
`
`Submit a clean copy and a tracked-change version of the label incorporating the
`recommendations in the attached package insert and medication guide on November 6,
`2012, to the NDA. In addition, please forward a courtesy copy to me via email.
`
`If you have any questions, contact me at 301-796-2466.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`_________________________________
`
`
`
`
`
`Philantha Montgomery Bowen
`
`
`
`
`
` Sr. Program Management Officer
` Division of Pulmonary, Allergy, and Rheumatology
` Products
` Office of Drug Evaluation II
` Center for Drug Evaluation and Research
`
`
`
`Enclosure: Package Insert
` Medication Guide
`
`
`
`Reference ID: 3213051
`
`2
`
`34 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this
`page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`PHILANTHA M BOWEN
`11/06/2012
`
`Reference ID: 3213051
`
`

`

`ACTION PACKAGE CHECKLIST
`
`NDA #
`I if:1#4/0r1gn_1al 1
`
`NDA Supplement #
`BLA Supplement #
`
`Xeljanz
`Proprietary Name:
`Established/Proper Name: tofacitinib
`Dosage Form:
`tablets, 5mg
`RPM: Philantha M. Bowen
`
`IfNDA, Efficacy Supplement Type:
`
`Applicant: Pfizer
`Agent for Applicant (if applicable):
`
`Division: DPARP
`
`NDAs and NDA Efficagy Supplements:
`
`505
`
`2 Ori ' al NDAs and 505
`
`2 NDA su
`
`lements:
`
`NDA Application Type: E 505(b)(1) D 505(b)(2) Listed drug(s) relied upon for approval (include NDA #(s) and drug
`Eflicacy Supplement: D 505(b)(1) I] 505(b)(2)
`name(s)):
`
`
`
`(A supplement can be either a (b)(l) or a (b)(2)
`regardless of whether the original NDA was a (b)(l)
`or a (b)(2). Consult page 1 of the 505(b)(2)
`Assessment or the Appendix to this Action Package
`Checklist.)
`
`Provide a brief explanation of how this product is diflerent from the listed
`drug.
`
`I] This application does not reply upon a listed drug.
`I] This application relies on literature.
`D This application relies on a final OTC monograph.
`D This application relies on (explain)
`
`For ALL gbuZ) applicationsI two months prior to EVERY actionI
`review the information in the 50512112! Assessment and submit the
`draft‘ to CDER 0ND 10 for clearance. Finalize the 505(b)(2)
`Assessment at the time of the approval action.
`
`On the day of approval, check the Orange Book again for any new
`patents or pediatric exclusivity.
`
`[I No changes El Updated Date of check:
`
`If pediatric exclusivity has been granted or the pediatric information in
`the labeling of the listed drug changed, determine whether pediatric
`information needs to be added to or deleted from the labeling of this
`drug.
`
`0
`°.° Actions
`
`Proposed action
`0
`0 User Fee Goal Date is November 21 2012
`
`0
`
`Previous actions (specifiz type and datefor each action taken)
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 5) lists
`the documents to be included in the Action Package.
`2 For resubmissions. (b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER 0ND IO unless the Assessment has been substantively revised (e.g., nrew listed drug, patent certification
`revised).
`
`Version: 1/27/12
`
`Reference ID: 321 3403
`
`

`

`NDA 203214
`
`Page 2
`
`'3'
`
`Ifaccelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`D Received
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions, see
`ht_tp://www fda.gov/downloads/Drugs/GuidanceConmlianceRegiilatoglnfomiation/Guida
`nces/ucm069965.-
`. Ifnot submitted, -
`lain
`O
`9.. Application Characteristics 3
`
`
`
`|Z| Standard El Priority
`Review priority:
`Chemical classification (new NDAs only):
`
`1
`
`D Fast Track
`El Rolling Review
`D Orphan drug designation
`
`[I Rx-to-OTC full switch
`[I Rx—to-OTC partial switch
`El Direct-to-OTC
`
`NDAs: Subpart H
`D Accelerated approval (21 CFR 314.510)
`[I Restricted distribution (21 CFR 314.520)
`Subpart I
`[I Approval based on animal studies
`
`BLAs: Subpart E
`I] Accelerated approval (21 CFR 601.41)
`E] Restricted distribution (21 CFR 601.42)
`Subpart H
`El Approval based on animal studies
`
`I] Submitted in response to a PMR
`El Submitted in response to a PMC
`El Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: E MedGuide
`E Communication Plan
`D ETASU
`I] MedGuide w/o REMS
`El REMS not required
`
`03° BLAs only: Ensure RMS—BLA Product Infomlation Sheetfor TBP and RMS—BLA Facility
`Information Sheetfor TBP have been completed and forwarded to OPI/OBI/DRM (Vicky
`Carter
`
`El Yes, dates
`
`v BLAs only: Is the product subject to oflicral FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I] Yes D No
`
`
`‘2' Public communications (approvals only)
`
`0 Ofiice of Executive Programs (OEP) liaison has been notified of action
`
`0
`Press Office notified of action (by OEP)
`
`0
`
`Indicate what types (if any) of information dissemination are anticipated
`
`
`
`FDA Talk Paper
`CDER Q&As
`Other
`
`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`supplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA. For
`example, if the application is a pending BLA supplement, then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version: “27/12
`
`Reference ID: 321 3403
`
`

`

`NDA 203214
`
`Page 3
`
`O
`°.° Exclusivity
`
`0
`
`Is approval of this application blocked by any type of exclusivity?
`
`E No
`
`D Yes
`
`0 NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
`drug or biologic for the proposed indication(s)? Refer to 21 CFR
`31 6.3(b)(13) for the definition of "same drug”for an orphan drug (i.e.,
`active moiety). This definition is NOT the same as that usedfor ADA
`chemical classification.
`
`o
`
`(b)(2) NDAs only: Is there remaining S-year exclusivity that would bar
`efiecfive approval of a 505 (b)(2) application)? (Note that, even ifexclusivity
`remains, the application may be tentatively approved iit is otherwise ready
`
`for approval.)
`
`o
`
`(b)(2) NDAs only: Is there remaining 3—year exclusivity that would bar
`efiecfive approval of a 505(b)(2) application? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ‘y‘it is othenvise ready
`for approval.)
`
`I] Yes
`E No
`If, yes, NDA/BLA #
`date exclusivity expires:
`
`If yes, NDA #
`exclusivity expires:
`
`and date
`
`D Yes
`DNo
`If yes, NDA #
`and date
`exclusivity expires:
`
`o
`
`(b)(2) NDAs only: Is there remaining 6—month pediatric exclusivity that
`would bar effective approval of a 505(b)(2) application? (Note that, even if
`If yes, NDA #
`exclusiw'ty remains, the application may be tentatively approved ifit is
`exclusivity expires:
`otherwise readyfor approval.)
`
`and date
`
`
`
`
`
`El Yes
`o NDAs only: Is this a single enantiomer that falls under the 10-year approval E No
`limitation of 505(u)? (Note that, even ifthe 10-year approval limitation
`.
`_
`.
`_
`_
`_
`_
`_
`Ifyes, NDA #
`and date 10-
`.
`perlod has not expired, the application may be tentatively approved IfIt Is
`-
`-
`-
`_
`year hmrtatron expires.
`,
`_
`.
`_
`'
`otherwise I eadyfor app] oval.)
`
`IX] Verified
`D Not applicable because drug is
`an old antibiotic.
`
`2 1 CFR 314.50(i)(1)(i)(A)
`D Verified
`
`21 CFR 314.50(i)(l)
`
`D No paragraph III certification
`Date patent will expire
`
`'3 N/A (no paragraph Iv certification)
`'3 Verified
`
`‘3‘ Patent Information (NDAs only)
`
`0
`
`Patent Information:
`
`Verify that form FDA-35423 was submitted for patents that claim the drug for
`which approval is sought.
`If the drug is an old antibiotic, skip the Patent
`
`Certification questions.
`
`0
`
`Patent Certification [505(b)(2) applications]:
`Verify that a certification was submitted for each patent for the listed drug(s) in
`the Orange Book and identify the type of certification submitted for each patent.
`
` O
`
`[505(b)(2) applications] If the application includes a paragraph 111 certification,
`it cannot be approved lmtil the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`o
`
`[505(b)(2) applications] For each paragraph IV certification, verify that the
`applicant notified the NDA holder and patent owner(s) of its certification that the
`patent(s) is invalid, unenforceable, or will not be infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Ifthe application does not include
`any paragraph IV certifications, mark "N/A " and skip to the next section below
`(Summary Reviews».
`
`Reference ID: 321 3403
`
`Version: 1/27/12
`
`

`

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` No
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`Version: 1/27/12
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`
`
`NDA 203214
`Page 4
`
`
` •
`
`
`
`[505(b)(2) applications] For each paragraph IV certification, based on the
`questions below, determine whether a 30-month stay of approval is in effect due
`to patent infringement litigation.
`
`Answer the following questions for each paragraph IV certification:
`
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`(1) Have 45 days passed since the patent owner’s receipt of the applicant’s
`notice of certification?
`
`
`
`(Note: The date that the patent owner received the applicant’s notice of
`certification can be determined by checking the application. The applicant
`is required to amend its 505(b)(2) application to include documentation of
`this date (e.g., copy of return receipt or letter from recipient
`acknowledging its receipt of the notice) (see 21 CFR 314.52(e))).
`
` If “Yes,” skip to question (4) below. If “No,” continue with question (2).
`
`(2) Has the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submitted a written waiver of its right to file a legal action for patent
`infringement after receiving the applicant’s notice of certification, as
`provided for by 21 CFR 314.107(f)(3)?
`
`
`If “Yes,” there is no stay of approval based on this certification. Analyze the next
`paragraph IV certification in the application, if any. If there are no other
`paragraph IV certifications, skip the rest of the patent questions.
`
`If “No,” continue with question (3).
`
`
`(3) Has the patent owner, its representative, or the exclusive patent licensee
`filed a lawsuit for patent infringement against the applicant?
`
`
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(f)(2))).
`
`
`If “No,” the patent owner (or NDA holder, if it is an exclusive patent licensee)
`has until the expiration of the 45-day period described in question (1) to waive
`its right to bring a patent infringement action or to bring such an action. After
`the 45-day period expires, continue with question (4) below.
`
`(4) Did the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submit a written waiver of its right to file a legal action for patent
`infringement within the 45-day period described in question (1), as
`provided for by 21 CFR 314.107(f)(3)?
`
`If “Yes,” there is no stay of approval based on this certification. Analyze the next
`paragraph IV certification in the application, if any. If there are no other
`paragraph IV certifications, skip to the next section below (Summary Reviews).
`
`If “No,” continue with question (5).
`
`
`
`
`Reference ID: 3213403
`
`

`

`NDA 203214
`
`Page 5
`
`(5) Did the patent owner, its representative, or the exclusive patent licensee
`bring suit against the (b)(2) applicant for patent infringement within 45
`days of the patent owner’s receipt of the applicant’s notice of
`certification?
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(t)(2)). Ifno written notice appears in the
`NDA file, confirm with the applicant Whether a lawsuit was commenced
`within the 45-day period).
`
`If "No, " there is no stay ofapproval based on this certification. Analyze the
`nart paragraph IV certification in the application, Vany. Ifthere are no other
`paragraph IV certifications, skip to the next section below (Summary
`Reviews).
`
`If "Yes, " a stay ofapproval may be in eflect. To determine ifa 30—month stay
`is in eflect, consult with the 0ND ADRA and attach a summary ofthe
`response.
`
`October 21, 2011
`
`6° Copy of this Action Package Checklist4
`
`November 6, 2012
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`'2' List of oflicers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only)
`
`Documentation of consent/non-consent by oflicers/employees
`
`'2' Copies of all action letters (including approval letter withfinal labeling)
`
`Action(s) and date(s)
`AP: November 6, 2012
`
`6° Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`Most recent draft labeling. Ifit is division-proposed labeling, it should be in
`track-changes format.
`
`November 6, 2012
`
`Original applicant-proposed labeling
`
`Example of class labeling, if applicable
`
`4 Fill in blanks with dates ofreviews, letters, etc.
`
`Version: 1/27/12
`
`Reference ID: 321 3403
`
`

`

`NDA 203214
`
`Page 6
`
`Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirstpage ofeach piece)
`
`Most-recent drafi labeling. Ifit is division-proposed labeling, it should be in
`track-changes format.
`
`Original applicant-proposed labeling
`
`Example of class labeling, if applicable
`
`>14 Medication Guide
`E Patient Package Insert
`[:1 Instructions for Use
`[:1 Device Labeling
`D None
`
`November 6, 2012
`
`October 21, 2011
`
`Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`
`0 Most-recent draft labeling
`
`8/14/12
`
`Proprietary Name
`0 Acceptability/non-acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s)
`0
`Ensure that both theproprietary name(s), ifany, and the generic name(s) are
`listed in the Application Product Names section ofDARRTS, and that the
`proprietaiy/trade name is checked as the ‘preferred ' name.
`
`Letters: 1/23/12; 4/17/12; 5/21/12;
`7/24/12
`
`Reviews: 1/20/12; 4/5/12; 5/1/12;
`5/21/12; 10/11/12
`
`Labeling reviews (indicate dates ofreviews and meetings)
`
`E RPM 12/2/11
`E DMEPA 6/11/12
`E DMPP/PLT (DRISK) 9/27/12
`E ODPD (DDMAC) 10/2/12
`I] SEALD
`E] css
`Other reviews CMC 8/2/12
`
`I] Not an AP action
`
`Administrative Reviews (e.g., RPMFiling Review Memo ofFiling Meeting) (indicate
`date ofeach review)
`All NDA (b)(2) Actions: Date each action cleared by (b)(2) Clearance Cmte
`NDA (b)(2) Approvals Only: 505(b)(2) Assessment (indicate date)
`
`12/19/11
`
`X Not a (b)(2)
`IE Not a (b)(2)
`
`NDAs only: Exclusivity Summary (signed by Division Director)
`
`Application Integrity Policy (AIP) Status and Related Documents
`hflpz/Iwww fda.gov/1CECI/EnforcementActions/Applicationlntegg'gPolicy/defaulthtm
`
`0 Applicant is on the AIP
`
`DYIZN°
`
`o
`
`This application is on the AIP
`
`D Yes E No
`
`o Ifyes, Center Director’s Exception for Review memo (indicate date)
`
`0 Ifyes, 0C clearance for approval (indicate date ofclearance
`communication)
`
`Pediatrics (approvals only)
`0 Date reviewed by PeRC July 11, 2012
`IfPeRC review not necessary, explain:
`Pediatric Page/Record (approvals only, must be reviewed by PERC before
`nalized)
`
`0
`
`5 Filing reviews for scientific disciplines should be filed behind the respective discipline tab.
`
`Version: 1127/12
`
`Reference ID: 321 3403
`
`

`

`NDA 203214
`
`Page 7
`
`Debarment certification (original applications only): verified that qualifying language was
`not used in certification and that certifications from foreign applicants are cosigned by
`US. agent (include certification)
`
`E Verified, statement is
`acceptable
`
`O
`0.0 Outgoing communications (letters, including response to FDRR (do not include previous
`action letters in this tab), emails, faxes, telecons)
`
`°2°
`
`Internal memoranda, telecons, etc.
`
`11/1/11; 12/19/11; 1/26/12;
`1/27/12; 2/27/12; 3/16/12;
`3/26/12 (2); 4/5/12; 4/17/12;
`5/15/12; 5/16/12; 5/22/12; 5/23/12;
`6/4/ 12; 6/20/12; 6/26/12; 6/28/12;
`7/9/12; 7/10/12; 7/19/12; 7/26/12;
`7/31/12; 8/6/12; 8/7/12; 8/20/12;
`10/5/12; 10/22/12; 10/26/12;
`11/1/12 2 ; 11/2/12 2 ; 11/6/12
`
`1/5/12; 3/30/12;11/6/12
`
`6/26/12; page 26
`
`6° Minutes of Meetings
`
`Regulatory Briefing (indicate date ofmtg)
`
`E No mtg
`
`Ifnot the first review cycle, any end-of-review meeting (indicate date ofmtg)
`
`El N/A or no mtg
`
`Pre-NDA/BLA meeting (indicate date ofmtg)
`EOP2 meeting (indicate date ofmtg)
`Other milestone meetings (e.g., EOP2a. CMC pilots) (indicate dates ofmtgs)
`
`D No mtg 2/16/l l
`D No mtg£é?£§m_3/7/11
`
`°2° Advisory Committee Meeting(s)
`
`0 Date(s) of Meeting(s)
`
`D No AC meeting
`
`5/9/ 12
`
`o
`
`48-hour alert or minutes, if available (do not include transcript)
`
`
`
`Oflice Director Decisional Memo (indicate datefor each review) 11/6/12
`
`Division Director Summary Review (indicate datefor each review)
`
`11/6/12
`
`
`
`Cross-Discipline Team Leader Review (indicate datefor each review) 7/20/12
`
`PMR/PMC Development Templates (indicate total number)
`
`3
`
`Clinical Reviews
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefor each review
`
`See CD'I'L review
`
`Clinical review(s) (indicate datefor each review)
`
`12/14/l 1; 6/26/12; 7/6/12; 9/26/12
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`Financial Disclosure reviews(s) or location/date if addressed in another review
`OK
`
`If no financial disclosure information was required, check here D and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`6/20/12; 6/26/12
`D None
`SEALD 10/22/12
`
`5;??91‘1