`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`202514Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`
`
`
`NDA # 202514
`
`EXCLUSIVITY SUMMARY
`
`
`
`
`
`SUPPL #
`
`
`
`
`
`HFD # 590
`
`Trade Name ZIOPTAN
`
`Generic Name tafluprost ophthalmic solution
`
`
`
`
`
`Applicant Name Merck Sharp & Dohme Corp.
`
`Approval Date, If Known
`
`PART I
`
`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.
`
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`
`
`
`
` YES
`
`
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`
`
`
`
`NO
`
`
`
`505(b)(1)
`
`c) 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
`
`
`
`NO
`
`
`
`
`
`
`
`
`
`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:
`
`
`
`
`
`
`
`d) Did the applicant request exclusivity?
`
`
`
`Reference ID: 3081587
`
`Page 1
`
`
`
`
`
`
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
`
`YES
`
`
`
`
`
`NO
`
`
`
`
` If the answer to the above question in YES is this approval a result of the studies submitted in
`
`NO
`
`response to the Pediatric Written Request?
`
`
`YES
`
`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
`
`
`
`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).
`
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(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
`
`
`
`NO
`
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`
`NDA#
`
`
`
`
`
`
`
`
`
`Reference ID: 3081587
`
`Page 2
`
`
`
`
`NDA#
`
`NDA#
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`
`Reference ID: 3081587
`
`Page 3
`
`
`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 any one 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
`
`
`
`NO
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`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
`
`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 of the 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)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`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
`
`
`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:
`
`
`
`NO
`
`
`
`
`
`
`
`
`
`
`(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?
`
`
`
`(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
`
`
`
`NO
`
`
`
` If yes, explain:
`
`
`
`
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`
`
`(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: 3081587
`
`Page 4
`
`
`
`
`
`
`
`
` If yes, explain:
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`
`(c)
`
`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 1) 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
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA 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?
`
`
`
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`Investigation #1
`
`
`
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`
`
`
`Reference ID: 3081587
`
`Page 5
`
`
`
`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(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`!
`!
`
`! NO
`! Explain:
`
`
`Investigation #1
`
`
`
`IND # 52080
`
`
`
`
`
`
`YES
`
`
`
`
`
`
`
`
`
`Investigation #2
`
`N/A
`
`IND #
`
`
`
`
`YES
`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(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? N/A
`
`Investigation #1
`
`
`
`
`
`
`
`
`
`YES
`Explain:
`
`
`Investigation #2
`
`
`YES
`Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3081587
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`Page 6
`
`
`
`(c) 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 (not just 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
`
`
`
`NO
`
`
`
`
`
`
`
`If yes, explain:
`
`
`
`=================================================================
`
`Name of person completing form: William M. Boyd, M.D.
`Title: Medical Officer
`Date: 01/31/2012
`
`
`Name of Office/Division Director signing form:
`Title:
`
`
`
`Form OGD-011347; Revised 05/10/2004; Formatted 02/15/2005
`
`
`
`Reference ID: 3081587
`
`Page 7
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`CONSTANTINE J MARKOS
`02/02/2012
`
`RENATA ALBRECHT
`02/02/2012
`
`Reference ID: 3081587
`
`
`
`
`
`
`
`
`
`MK2452 - Tafluprost Ophthalmic Solution Single Dose Container
`
`Debarment Certification
`
`1
`
`‘
`
`
`
`
`
`
`
`
`
`
`
`
`
`As required by §306(l<)(1) of 21 U.S.VC. 33Sa(l<)( 1), we hereby cenify that, in connection
`
`
`
`
`
`
`
`
`
`
`
`
`
`with this application, Merck Sharp & Dohme Corp, a subsidiary of Merck & C0,, lnc.
`(Merck), did not and will not use in any capacity the services of any person debarred
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`under subsections 306(a) or (b) of the Act.
`-
`
`
`0M;- 4" Zr
`
`Chitkala
`Kalidas,
`PhD.
`
`Director
`
`
`WW Reg. Liaison
`
`
`
`
`
`“1 De cam/oer 020/0
`Date
`
`MK-2452 DocumentS
`
`
`Restricted ‘3 Confidential - Limited Access
`
`
`
`
`
`,
`
`30—Nov-2010
`
`
`
`
`ACTION PACKAGE CHECKLIST
`
`Proprietary Name: ZIOPTAN
`Established/Proper Name: tafluprost 0.0015%
`Dosage Form:
`Ophthalmic Solution
`
`Apphcant: Merck Sh?” & Dohme C0!“
`Agent for Apphcant (if apphcable):
`
`RPM: Constantine J. Markos, B.S., Pharm.D., R.Ph.
`
`Division: Division of Transplant and Ophthalmology Products
`
`NDAs and NDA Efficag Supplements:
`
`50519112) Origg'al NDAs and 5051;9112) NDA supplements:
`
`NDA Application Type: E 505(b)(l) D 505(b)(2) Listed drug(s) relied upon for approval (include NDA #(s) and drug
`Efficacy Supplement: D 505(b)(1) D 505(b)(2)
`name(s)):
`
`0 User Fee Goal Date is 03/13/2012
`
`(A supplement can be either a (le) 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 different from the listed
`drug.
`
`D This application does not reply upon a listed drug.
`I] This application relies on literature.
`I] This application relies on a final OTC monograph.
`I] This application relies on (explain)
`
`For ALL (9112) applications, two months prior to EVERY actiona
`review the information in the 50519112) Assessment and submit the
`draft2 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.
`
`E No changes D 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.
`
`Actions
`
`Proposed action
`
`0
`
`Previous actions (spectfy 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 re-submissions, (b)(2) applications must be cleared before the action, but it is not necessary to re-submit the draft 505(b)(2)
`Assessment to CDER 0ND IO unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
`revised).
`
`Version: 01/27/2012
`
`Reference ID: 3088870
`
`
`
`NDA# 202514
`
`Page 2
`
`'3'
`
`If accelerated approval or approval based on efficacy studies in animals. were promotional
`materials received?
`
`lain
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions. see
`hgpzl/www fda.gov/downloads/Drugs/GuidanceCornplianceReggglatoghiformation/Guida
`nces/ucm069965.-
`. Ifnot submitted, -
`
`D Received
`
`'3' Application Characteristics 3
`
`|Z| Standard El priority
`Review priority:
`Chemical classification (new NDAs only):
`
`1
`
`D Fast Track
`D Rolling Review
`El Orphan drug designation
`
`[I Rx-to-OTC full switch
`[I Rx-to-OTC partial switch
`El Direct-to-OTC
`
`NDAs: Subpart I-l
`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: I] MedGuide
`I] Communication Plan
`D ETASU
`I] MedGuide w/o REMS
`E REMS not required
`
`'2' BLAs only: Ensure RMS—BLA Product Information Sheetfor THP and RMS—BLA Facilitv
`Information Sheetfor TBP have been completed and forwarded to OPl/OBI/DRM (Vicky D Yes, dates
`T son
`
`v BLAs only: Is the product subject to oflicral FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I] Yes
`
`[I No
`
`
`
`
`6° Public communications (approvals only)
`
`0 Oflice 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
`
`
`
`E HHS Press Release
`El FDA Talk Paper
`El CDER Q&As
`D 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: 01/27/2012
`
`Reference ID: 3088870
`
`
`
`NDA# 202514
`
`Page 3
`
`O
`0.0 Exclusivity
`
`0
`
`Is approval of this application blocked by any type of exclusivity?
`
`E No
`
`D Yes
`
`o NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
`drug or biologic for the proposed indication(s)? Refer to 21 CFR
`316.3(b)(13)fi)r the definition of "same drug"for an olphan drug (i.e.,
`active moiety). This definition is NOT the same as that usedfor NDA
`chemical classification.
`
`0
`
`(b)(2) NDAs only: Is there remaining 5-year exclusivity that would bar
`efl'ective approval of a 505(b)(2) application)? (Note that, even ifexclusiiitv
`remains, the application may be tentatively approved ifit is otherwise ready
`for approval.)
`
`o
`
`(b)(2) NDAs only: Is there remaining 3—year exclusivity that would bar
`effective approval of a 505(b)(2) application? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ifit is othenvise ready
`for approval.)
`
`I
`
`(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
`exclusivity remains, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`o NDAs only: Is this a single enantiomer that falls under the 10-year approval
`limitation of 505(u)? (Note that, even ifthe 10—year approval limitation
`period has not expired, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`‘2‘ Patent Information (NDAs only)
`
`0
`
`Patent Information:
`
`Verify that form FDA-3542a 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 III certification,
`it cannot be approved until the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`
`
`I] Yes
`E No
`If, yes, NDA/BLA #
`date exclusivity expires:
`
`
`
`If yes, NDA #
`exclusivity expires:
`
`and date
`
`D Yes
`D No
`If yes, NDA #
`and date
`exclusivity expires:
`
`If yes. NDA #
`exclusivity expires:
`
`and date
`
`[I Yes
`E No
`If yes, NDA #
`and date 10-
`year limitation expires:
`
`IX] Verified
`PP
`g
`D Not a
`licable because dm _ is
`an old antibiotic.
`
`21 CFR 314.50(i)(1)(i)(A)
`El Verified
`
`21 011R 314.5090)
`
`D No paragraph III certification
`Date patent will expire
`
`E] N/A (no paragraph IV certificatitm)
`D Verified
`
`0
`
`[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: 3088870
`
`Version: 01/27/2012
`
`
`
` Yes
`
` No
`
` Yes
`
` No
`
` Yes
`
` No
`
` Yes
`
` No
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Version: 01/27/2012
`
`NDA# 202514
`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:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(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: 3088870
`
`
`
`NDA# 202514
`
`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(1)(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
`nextparagraph IV certification in the application, iany. Ifthere are no other
`paragraph IV certfiications, skip to the next section below (Summary
`Reviews).
`
`If "Yes, ” a stay ofapproval may be in eject. 1'0 determine ifa 30—month stay
`is in eflect, consult with the 0ND ADRA and attach a summary ofthe
`response.
`
`
`
`0:0 Copy of this Action Package Checklist4
`
`List of officers/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
`
`'3' Copies ofall action letters (includingApproval Letter withfinal labeling)
`
`2:1:3%;7213: li'atfilfln/l0[2012
`
`~20 Package Insert (write :mbmission/communication date at upper right offirstpage ofPI)
`
`Most recent draft labeling. Ifit is division-proposed labeling, it should be in
`haCk-claanses fomatz,
`
`Enclosed dated 01/23/2012
`
`Original applicant-proposed labeling
`Example of class labeling, if applicable
`
`Enclosed dated 0l/07l2011 ,
`N/A
`
`‘
`
`4 Fill in blanks with dates of reviews, letters, etc.
`
`Version: 01/27/2012
`
`Reference ID: 3088870
`
`
`
`NDA# 202514
`
`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. If it is division-proposed labeling, it should be in
`track-changes format.
`
`Original applicant-proposed labeling
`
`Example of class labeling, if applicable
`
`Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`
`0 Most-recent draft labeling
`
`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 genetic name(s) are
`listed in the Application Product Names section ofDARRTS, and that the
`proprietaIy/h'ade name is checked as the 'preferred ’ name.
`
`Medication Guide
`
`E Patient Package Insert
`[:1 Instructions for Use
`[:1 Device Labeling
`D None
`
`Enclosed dated 01/23/2012
`
`Enclosed dated 01/07/201 1
`
`N/A
`
`Enclosed dated 1 1/04/2011
`
`Review 04/15/201 l—Denied
`Letter 04/15/201 l—Denied
`
`Review 08/31/201 l—Accepted
`Letter 08/31/201 l--Accepted
`Review 02/09/2012—Accepted
`
`|___| RPM
`[2 DMEPA 08/24/2011
`|Z| DMPP/PLT (DRISK)
`Consult 11/01/2011;
`Review 11/03/201 1
`
`E ODPD (DDMAC)
`Consult 06/08/2011;
`Review 10/19/2011;
`Consult 11/01/2011.
`Review 11/03/201 1
`
`Other reviews
`
`07/08/201 1
`
`X Not a (b)(2)
`X Not a (b)(2)
`
`
`
`Labeling Reviews (indicate dates ofreviews and meetings)
`
`Administrative Reviews (e.g., RPM Filing Review Memo ofFiling Meeting) (indicate
`date ofeach review)
`All NDA (b)(2) Actions: Date each action cleared by (b)(2) Clearance Committee
`NDA (b)(2) Approvals Only: 505(b)(2) Assessment (indicate date)
`
`NDAs only: Exclusivity Summary (signed bv Division Director)
`
` DYE“
`
`D Yes
`
`12 No
`
`Application Integrity Policy (AIP) Status and Related Documents
`ht_tQ://www fda.gov/ICECI/EnforcementActions/Applicationlntem‘flPolicy/defaulthtm
`
` o
`
`0 Applicant is on the AIP
`
`O
`
`This application is on the AIP
`
`Ifyes, Center Director’s Exception for Review memo (indicate date)
`
`0 Ifyes, 0C clearance for approval (indicate date ofclearance
`communication)
`
`D Not an AP action
`
`5 Filing reviews for scientific disciplines should be filed behind the respective discipline tab.
`
`Version: 01/27/2012
`
`Reference ID: 3088870
`
`
`
`NDA# 202514
`
`Page 7
`
`Pediatrics (Approvals only)
`0 Date reviewed by PeRC 05/25/2011
`IfPeRC review not necessary, explain: Accgptable
`Pediatric Page/Record (Approvals only, must be reviewed by PeRC before
`
`0
`
`°2' Debarment certification (original applications only): verified that qualifying language was
`not used in certification and that certifications from foreign applicants are co-signed by
`US. agent (include certification)
`
`Outgoing Communications (letters, including response to FDRR (do not include previous
`action letters in this tab), e—mails, faxes, tele-cons, etc.
`
`E Verified, statement is
`acceptable
`
`01/28/2011; 02/15/2011;
`03/02/201 1; 03/08l201 l;
`03/22/201 1; 05/05/201 1;
`05/10/2011; 05/20/2011;
`06/06/2011; 06/17/2011;
`07/06/2011; 07/19/2011;
`08/04/201 1; 08/29/201 1;
`01/09/2012; 02/08/2012
`
`Internal memoranda tele-cons, etc.
`
`Minutes of Meetings
`Regulatory Briefing (indicate date ofmtg) E No mtg
`
`
`Ifnot the first review cycle, any end-of-review meeting (indicate date ofmtg.) D N/A or.no mtg None
`
`Pre-NDA meeting (indicate date ofmtg.)
`D No mtg 08/13/2010
`
`EOP2 meeting (indicate date ofmtg.)
`
`D No mtg 08/24/2009
`
`Other milestone meetings (e.g._. EOP2a, CMC pilots) (indicate dates ofmtgs.)
`
`‘20 Advisory Committee Meeting(s)
`
`Clinical Guidance 10/12/2005
`
`E No AC meeting
`
`
`
`Dam) ofMeefing(s)
`
`48—hour alert or minutes, if available (do not include h'anscn'pt)
`
`O o
`
`Office Director Decisional Memo (indicate datefor each review)
`
`Deputy/Division Director Summary Review (indicate datefor each review)
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`PMR/PMC Development Templates (indicate total number)
`
`11/07/2011;
`I None
`..
`02/10/2012
`11/07/2011;
`|'_'] None
`1 1/07/2011; 02/01/2012;
`02/10/2012
`I] None
`02/01/2012
`
`11/07/2011;
`
`E None
`
`
`Clinical Reviews
`
`
`0
`Clinical Team Leader Review(s) (indicate datefor each review)
`
`11/07/201 1502/01/2012
`
`0
`
`Clinical Review(s) (indicate datefor each review)
`
`02/28/2011 09/28/2011
`
`OR
`Ifno financial disclosure information was required, check here I] and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`09/28/2011 Rev1ew on Page 7.
`
`6 Filing reviews should be filed with the discipline reviews.
`
`Version: 01/27/2012
`
`Reference ID: 3088870
`
`
`
`NDA# 202514
`
`Page 8
`
`Clinical reviews from immunology and other clinical areas/Divisions/Centers (indicate
`date ofeach review)
`
`E None
`
`Controlled Substance Staffreview(s) and Scheduling Recommendation (indicate date of
`each review)
`
`E Not applicable
`
`Risk Management
`REMS Documents and Supporting Statement (indicate date(s) ofsubmission(s))
`REMS Memo(s) and letter(s) (indicate date(s))
`Risk management review(s) and recommendations (including those by OSE and
`CSS) (indicate date ofeach review and indicate location/date ifincorporated
`into another review)
`
`D81 Clinical Inspection Review Summary(ies) (include copies ofD8] letters to
`investigators)
`
`D None requested
`Consult 02/24/2011;
`Letter 06/09/2011;
`Review 06/27/201 1;
`Letter 07/28/201 1
`
`
`
`
`Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`Statistical Division Director Review(s) (indicate datefor each review)
`
`E None
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each review)
`
`E None
`[I None 03/22/2011;
`07/20/2011
`
`Clinical Pharmacology Division Director Review(s) (indicate datefor each review) E None
`
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`E None
`(gals/31:31 02/16/201 1;
`
`03‘ D81 Clinical Pharmacology Inspection Review Summary (include copies ofDSI letters)
`
`’2' Pharmacology/Toxicology Discipline Reviews
`
`
`0 AD P/T Review(s) (indicate datefor each revieu)
`
`D None
`
`07/25/2011
`
`Supervisory Review(s) (indicate datefor each review)
`
`E None
`
`0
`
`Pharm/ on review(s), including referenced IND reviews (indicate datefor each
`review
`
`DN