CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208026Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 208026
`
`Trade Name Jentadueto XR
`
`Generic Name (linagliptin and metformin hydrochloride extended-release) tablets
`
`Applicant Name Boehringer Ingelheim Pharmaceuticals, Inc.
`
`
`
`Approval Date, If Known May 27, 2016
`
`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)(1), 505(b)(2) or efficacy supplement?
`
` YES
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`b) 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.
`
`Three clinical studies were completed by the applicant, one study for bioavailability
`(Study 1288.8) and two studies for bioequivalence (Studies 1288.9 and 1288.11) were
`completed. Per the note above, BA and BE studies do not qualify. The applicant
`acknowledges only BA and BE studies were completed for this application, they refer to
`NDA 201280 and have right of reference to NDA 021748 for safety and efficacy.
`
`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: 3938094
`
`Page 1
`
`

`

`N/A
`
`c) Did the applicant request exclusivity?
`
` YES
`
`NO
`
`If the answer to (c) is "yes," how many years of exclusivity did the applicant request?
`
`N/A
`
`d) 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 response to the Pediatric Written Request?
`
`
` N/A
`
`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
`
`Reference ID: 3938094
`
`Page 2
`
`

`

`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`
`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 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 201280
`NDA# NDA 021748
`NDA# NDA 201281
`
`Tradjenta (linagliptin) tablets
`Glumetza (metformin extended-release) tablets
`Jentadueto (linagliptin and metformin) tablets
`
`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 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."
`
`Reference ID: 3938094
`
`Page 3
`
`

`

`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
`
`NO
`
`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
`
`NO
`
`
`
`(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:
`
`
`
`
`
`Reference ID: 3938094
`
`Page 4
`
`

`

`(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?
`
` YES
`
`NO
`
` If yes, explain:
`
`
`
`(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
`
`Investigation #2
`
`
`
`YES
`
`YES
`
`
`
`NO
`
`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
`
`Reference ID: 3938094
`
`Page 5
`
`

`

`the effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`YES
`
`YES
`
`NO
`
`NO
`
`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(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`
`
`!!
`
`! NO
`! Explain:
`
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`Investigation #1
`
`IND #
`
`YES
`
`
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`
`
`
`
`Reference ID: 3938094
`
`Page 6
`
`

`

`(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?
`
`!!
`
`
`! NO
`! Explain:
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`Investigation #1
`
`
`
`YES
`Explain:
`
`
`
`
`Investigation #2
`
`
`
`YES
`Explain:
`
`
`
`
`(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: Richard Whitehead, M.S.
`Title: DMEP RPM
`Date: May 27, 2016
`
`
`Name of Office/Division Director signing form: Jean-Marc Guettier, M.D.
`Title: DMEP Director
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3938094
`
`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/
`----------------------------------------------------
`
`RICHARD E WHITEHEAD
`05/27/2016
`
`JEAN-MARC P GUETTIER
`05/27/2016
`
`Reference ID: 3938094
`
`

`

`
`
`
`ACTION PACKAGE CHECKLIST
`
` APPLICATION INFORMATION1
`
`
`NDA # 208026
`
`
`
`
`
`l
`
`
`
`
`
`
`
`Jentadueto XR
`Proprietary Name:
`
`
`
`
`
`
`
`
`
`
`Applicant: Boehringer Ingelheim Pharmaceutical, Inc
`linagliptin and metformin
`Established/Proper Name:
`
`
`hydrochloride extended-release
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Dosage Form: 2.5 mg/ 1000 mg and 5 mg/ 1000 mg tablets
`
`
`
`RPM: Richard Whitehead
`
`
`
`
`
`
`
`
`
`
`Division: Division of Metabolism and Endocrinology Products
`
`
`
`
`
`
`
`
`
`
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
`
`
`
`
`NDA Application Type:
`
`
`IX] 505(b)(1)
`
`
`
`
`[I 505(b)(2)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0 Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER 0ND IO for clearance.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0 Check Orange Book for newly listed patents and/or
`
`
`
`
`exclusivity (including pediatric exclusivity)
`
`
`
`
`
`
`
`
`E] No changes
`
`
`
`
`
`
`I] New patent/exclusivity (notify CDER 0ND 10)
`Date of check:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Note: Ifpediatric exclusivity has been granted or the pediatric
`
`
`
`
`
`
`
`
`
`
`information in the labeling ofthe listed drug changed, determine whether
`
`
`
`
`
`
`
`
`
`
`
`
`pediatric information needs to be added to or deletedfrom the labeling of
`
`
`this drug.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`, ,, i
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`El Received
`
`. Actions
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`If accelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Note: Promotional materials to be used within 120 days after approval must have been
`
`
`
`
`submitted (for exceptions, see
`httpflyxwv.idigov/downloads/Drugs/GuidanceComplianceRegulatorvlnformation/Guida
`
`
`
`
`
`
`nces/ucn1069965pd . If not submitted, explain
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`
`
`
`
`
`
`
`
`
`the documents to be included in the Action Package.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2 For resubmissions, 505 (b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`:sessment to CDER 0ND IO unless the Assessment has been substantively revised (e. g., new listed drug, patent certification
`
`vised).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`‘ 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.
`
`
`
`
`
`
`Version: 2/ 12/1 6
`
`
`
`
`
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`

`

`NDA 208026
`
`
`Page 2
`
`
`
`
`
`
`
`
`
`
`Standard
`Review priority:
`1:] Priority
`
`
`
`
`
`
`
`Type 4—New Combination
`Chemical classification (new NDAs only):
`
`
`
`
`
`
`
`(confirm chemical classification at time ofapproval)
`
`
`
`
`
`
`
`[:1 Fast Track
`
`
`
`D Rolling Review
`
`
`
`
`[:I Orphan drug designation
`
`
`
`
`[:l Breakthrough Therapy designation
`(NOTE: Set the submission property in DARR TS and notify the CDER Breakthrough Therapy Program Manager;
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Refer to the “RPM B T Checklistfor Considerations after Designation Granted”for other required actions: CS T SharePoinI)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`I:I Rx-to-OTC full switch
`
`
`
`[:I Rx—to-OTC partial switch
`
`
`[:I Direct-to-OTC
`
`
`
`
`
`
`
`
`NDAs: SubpartH
`
`
`
`
`
`
`E] Accelerated approval (21 CFR 314.510)
`
`
`
`
`
`[I Restricted distribution (21 CFR 314.520)
`
`Subpart I
`
`
`
`
`
`E] Approval based on animal studies
`
`
`
`
`
`
`
`
`
`
`
`
`E] Submitted in response to a PMR
`
`
`
`
`
`
`
`[:I Submitted in response to a PMC
`
`
`
`
`
`
`
`
`El Submitted in response to a Pediatric Written Request
`
`
`
`Comments:
`
`
`
`
`
`
`BLAs: SubpartE
`
`
`
`
`
`
`E] Accelerated approval (21 CFR 601.41)
`
`
`
`
`
`
`El Restricted distribution (21 CFR 601.42)
`
`Subpart H
`
`
`
`
`
`[I Approval based on animal studies
`
`
`
`
`
`
`REMS: El MedGuide
`
`
`El Communication Plan
`
`
`[I ETASU
`
`
`
`
`El MedGuide w/o REMS
`
`
`
`
`I] REMS not required
`
`
`
`
`
`
`
`D Yes El No
`
`
`
`
`
`
`
`
`
`@ YEN
`None
`
`
`
`
`
`I] FDA Press Release
`
`
`
`
`FDA Talk Paper
`CHIN]
`
`
`CDER Q&As
`Other
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Is the product subject to official FDA lot release per 21 CFR 610.2
`’2' BLAs only:
`
`
`(approvals only)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`Office of Executive Programs (OEP) liaison has been notified of action
`
`
`
`
`
`
`
`
`
`
`
`
`
`Indicate what types (if any) of information were issued
`
` 0
`
`
`
`
`O
`0.0
`
`
`
`
`Exclusivity
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
`
`
`
`
`NCE, 3-year, pediatric exclusivity)?
`
`
`
`
`
`
`'1‘ Patent Information (NDAS only)
`
`
`
`
`
`
` o
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`Patent Information:
`Verified
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Verify that form FDA—3542a was submitted for patents that claim the drug for
`‘
`
`
`
`
`
`
`which approval is sought.
`El Not applicable because drug is
`
`
`
`
`
`an old antibiotic.
`
`
`
`
`
`
`
`CONTENTS OF ACTION PACKAGE
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`‘3 List of officers/employees who participated in the decision to approve this application and
`consentedtobeIdentlfiedonthlshst(approvalmly)
`.,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Documentation of consent/non—consent by officers/employees
`
`
`
`
`
`
`
`
`
`
`
`
`
`E muted
`
`IXI Included
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`

`

`NDA 208026
`
`
`Page 3
`
`
`
`|
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`I AP; May27, 2016
`
`E] Included
`
`Action Letters
`
`
`3 Copies ofall action letters (includingapproval letterwithfinallabeling)
`
`
`
`Labeling
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Package Insert (write submission/communication date at upper right offirst page ofPI)
`
`
`
`XI Included
`
`
`Most recent draft labeling (ifit is division-proposed labeling, it should be in
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`see aCtion letter dated:
`
`
`
`
`
`
`
`
`track-changesformat)
`
` Original applicant-proposed labeling
`
`
`
`
`
`
`
`
`
`[XI Medication Guide
`
`
`
`
`Patient Package Insert
`DUE]
`
` v Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`
`
`
`
`
`
`
`
`
`
`
`
`Instructions for Use
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`submission/communication date at upper right offirst page ofeach piece)
`
`
`
`
`Device Labeling
`
`
`
`IZI‘EI
`None
`
`Included
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`see action letter dated:
`0 Most-recent draft labelmg (ifit zs dzvtszon-proposed labeling, it should be in
`
`
`
`
`
`
`
`May 27, 2016
`track-changesformat)
`
`
`
`
`
`E] Included
` Original applicant—proposed labeling
`
`
`
`
`
`i
`
`
`
`_|
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Labels (full color carton and immediate-container labels) (write
`
`
`
`
`
`
`
`
`
`
`
`
`
`submission/communication date on upper right offirst page ofeach submission)
`
`
`
`
`
`
`
`
`
`x»:-
`
`
`
`
`Included
`
`
`
`
`
`
`see action letter dated:
`
`
`May 27, 2 0 1 6
`
`
`
`
`0 Most-recent draft labeling
`
`
`
`
`
`
`, 0: Proprietary Name
`
`
`
`
`
`0 Acceptability/non-acceptability letter(s) (indicate date(s))
`
`
`
`
`0
`Review(s) (indicate date(s)
`
`9-1
`9-1
`
`
`
`
`
`
`
`
`
`
`'1’ Labeling reviews (indicate dates ofreviews)
`
`
`
`
`
`Administrative / Regulatory Documents
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`v RPM Filing Review4/Memo of Filing Meeting (indicate date ofeach review)
`
`
`
`
`
`
`
`
`
`
`
`
`’3‘ A11 NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`
`
`
`
`
`
`
`
`
`
`v NDAs only: Exclusivity Summary (signed by Division Director)
`
`
`
`RPM: PLR Format 9-15-15
`
`
`
`DMEPA: 4-29-16; 3-15-16
`
`
`
`DMPP/PLT: 5 —05- 1 6
`
`
`
`
`OPDP: XI None
`None
`SEALD:
`
`
`
`
`
`CSS: E None
`
`
`
`
`Product Quality XI None
`Other: DPMH PLLR 5-02-16
`
`
`
`
`
`
`
`
`9- 1 5 - 1 5
`
`
`A
`
`
`
`Not a (b)(2)
`
`
`
`
`
`XI Included
`
`
`
`
`
`
`*3 No
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`v Application Integrity Policy (AIP) Status and Related Documents
`litp://WWW.fda_.gov/lCEClx’EnforcementActions/Applicationlntegritfiolicv/default.htm
`
`‘
`
`'
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`

`

`NDA 208026
`
`
`Page 4
`
`
`
`
`o
`
`
`
`
`
`
`This application is on the AIP
`
`
`
`
`
`
`
`
`
`
`
`o
`If yes, Center Director’s Exception for Review memo (indicate date)
`
`
`
`D Yes
`
`
`
`NoA
`
`
`
`
`
`9 v
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`D Not an AP action
`If yes, OC clearance for approval (indicate date ofclearance
`
`
`
`
`
`
`communication)
`
`
`
`
`
`
`Pediatrics (approvals only)
`
`
`
`
`
`
`- Date reviewed by PeRC 4-13-16
`
`
`
`
`
`If PeRC review not necessary, explain:
`
`
`
`
`
`
`02' Breakthrough Therapy Designation
`
`
`
`
`
`
`
`
`o
`
`
`0
`
`
`
`
`
`
`
`
`Breakthrough Therapy Designation Letter(s) (granted, denied, an/or rescinded)
`
`
`
`
`
`
`
`
`
`
`CDER Medical Policy Council Breakthrough Therapy Designation
`
`
`
`
`
`
`
`
`Determination Review Template(s) (include only the completed template(s) and
`
`
`
`
`not the meeting minutes)
`
`
`
`
`
`
`
`CDER Medical Policy Council Brief — Evaluating a Breakthrough Therapy
`
`
`
`
`
`
`
`
`Designation for Rescission Template(s) (include only the completed template(s)
`
`
`
`
`
`and not the meeting minutes)
`
`
`
`
`
`
`
`
`
`
`
`
`5—27-16; 5-3-16; 3-24-16; 10-02—
`
`
`
`
`15; 9-18—15; 9-14—15; 7—31—15
`
`
`
`
`
`
`
`N/A
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(completed CDER MPC templates can befound in DARRTS as clinical reviews or on
`
`
`
`
`
`
`the MPC SharePoint Site)
`
`
`
`
`
`
`
`
`
`
`
`
`‘3‘ Outgoing communications: letters, emails, and faxes considered important to include in
`
`
`
`
`
`
`
`
`
`
`
`
`
`the action package by the reviewing office/division (e.g., clinical SPA letters, RTF letter,
`
`
`
`
`
`
`
`
`
`
`
`
`Formal Dispute Resolution Request decisional letters, etc.) (do not include OPDP letters
`
`
`
`
`
`
`
`
`
`
`
`regarding pre—launch promotional materials as these are non-disclosable; do not include
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Master File letters; do not include previous action letters, as these are located elsewhere
`
`
`in package)
`
`
`
`
`
`
`
`
`Internal documents: memoranda, telecons, emails, and other documents considered
`
`
`
`
`
`
`
`
`
`
`
`
`important to include in the action package by the reviewing office/division (e.g.,
`
`
`
`
`
`
`
`
`Regulatory Briefing minutes, Medical Policy Council meeting minutes)
`
`
`
`
`‘2' Minutes of Meetlngs
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`o
`If not thefirst review cycle, any end-of--review meeting (indicate date ofmtg)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`N/A
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Mid-cycle Communication (indicate date ofmtg)
`
`
`
`
`
`
`
`
` Late-cycle Meeting (indicate date ofmtg)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Other milestone meetings (e.g., EOP2a, CMC focused milestone meetings)
`
`
`
`
`
`
`(indicate dates ofmtgs)
`
`
`
`
`’1' Advisory Committee Meeting(s)
`
`
`
`
`
`
`
`
`
`
`
`
`
`No AC meeting
`
`
`
`
`
`0 Date(s) of Meeting(s)
`
`
`
`
`
`
`Decisional and Summary Memos
`
`
`
`
`
`
`
`
`
`
`
`
`
`'3' Office Director Decisional Memo (indicate datefor each review)
`
`E None
`
`
`
`XI None
`
`
`
`
`
`
`
`
`
`Division Director Summary Review (indicate datefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`Cross-D1301p11ne Team Leader Review (indicate datefor each review)
`
`PMR/PMC Development Templates(indicate totalnumber)
`
`
`
`
`
`
`
`Clinical
`
`
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`None
`
`
`
`
`
`
`[I None
`
`
`
`
`
`
`
`5-27-16
`
`
`
`
`
`

`

`NDA 208026
`
`
`
`
`Page 5
`
`
`
`‘3‘ Clinical Reviews
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`
`
`0
`
`
`0
`
`
`
`
`
`
`
`'2 None
`
`
`
`
`
`
`
`
`
`0 v
`
`
`
`
`
`
`Clinical Team Leader Review(s) (indicate datefor each review)
`El Noseparate review 5-27-16
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5-18-16; 9-24- 15
`Clinical review(s) (indicate datefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`Social scientist review(s) (if OTC drug) (indicate datefi2r each review)
`El None
`
` See clinical review (page 11)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`dated: 5-18-16
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`If no financial disclosure information was required, check here E] and include a
`
`
`
`
`
`
`
`
`
`
`review/memo explaining why not (indicate date ofreview/memo)
`
`
`
`
`
`
`
`
`
`
`0:. Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`
`
`
`
`date ofeach review)5
`
`
`
`
`
`
`
`
`
`Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of E N/A
`
`
`
`
`each review)
`
`
`
`'3‘ Risk Management
`
`
`
`
`
`
`
`
`
`REMS Documents and REMS Supporting Document (indicate date(s) of
`
`submission(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)
`
`
`
`
`
`
`
`
`
`
`OSI Clinical Inspection Review Summary(ies) (include copies of OSI letters to
`investigators)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`None
`
`
`
`
`
`El None requested
`
`
`
`
`
`Clinical Microbiology
`
`
`
`
`
`
`
`
`
`
`
`‘3' Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`
`Biostatistics
`
`
`[Z None
`
`
`IX! None
`
`
`
`
`
`
`
`
`
`El No separate review
`
`I] None
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Statistical Division Director Review(s) (indicate date for each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Statistical Review(s) (indicate datefor each review)
`
`
`
`Clinical Pharmacology
`El None
` Clinical Pharmacology Team Leader Review(s) (indicate date for each review)
`
`
`
`
`
`
`
`
`
`Clinical Pharmacology Division Director Review(s) (indicate datefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`‘3' OSI Clinical Pharmacology Inspection Review Summary (include copies of0S] letters)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`D No separate review
`
`
`
`I] No separate review
`
`D None
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`D No separate review
`
`
`
`IE No separate review
`
`
`
`
`
`.4
`
`
`
`4-27-16; 10-2-15
`
`3—92-96; 3—15-16Q); 249-16; 12-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`For Part 3 combination products, all reviews from the reviewing Center(s) should be entered into the official archive (for further
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`instructions, see “Section 508 Compliant Documents: Process for Regulatory Project Managers” located in the CST electronic
`
`repository).
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`

`

`NDA 208026
`
`
`
`
`Page 6
`
`
`
`
`
`Nonclinical
`E] None
`
`9
`O
`
`
`
`
`' Pharmacology/Tox1cology D1501p11ne Revrews
`
`
`
`
`
`
`o
`
`
`
`
`
`
`
`
`
`
`ADP/T Rev1ew(s) (indicate datefor each revzew)
`
`
`
`
`
`
`
`
`
`Pharm/tox review(s) Including referenced IND reviews (indicate datefor each
`
`
`
`
`
`
`
`
`
`
`
`
`review)
`
`
`
`
`
`
`
`
`
`
`
`'1‘ Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`.
`
`
`
`for each revzew)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'2‘ Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`
`
`
`
`
`
`‘2' ECAC/CAC report/memo of meeting
`
`
`
`
`
`
`WIXIM"No separate rev1ew
`IE No separate rev1ew
`
`
`
`5-04- 16; 9- 11- 15
`
`
`
`
`
`
`
`
`[Z None
`
`
`
`
`
`
`No care
`
`
`
`
`[XI None
`
`
`
` Supervisory Review(s) (indicate datefor each revzew)
`review)
`
`
`
`
`
`
`
`
`
`
`
`
`‘1’ OSI Nonclinical Inspection Review Summary (include copies of OSI letters)
`
`
`
`XI None requested
`
`
`
`
`Product Quality
`
`
`
`
`El None
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Tertiary review (indicate datefor each revzew)
`IE None
`Secondary review (eg., Branch Chief) (indicatedatefor each review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`INN-IntegratedQuality Assessment (contams "the" Executlve Summary and thepr1mary“
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`reviews from each product quality review discipline) (indicate datefor each
`4-18-16
`
`
`None
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` El Categorical Exclusion (indicate review date)(all original applications and
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`all eflicacy supplements that could increase the patient population)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`[:| Review & FONSI (indicate dateWof review)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`El Facilities inspections (action must be taken prior to the re—evevaluation date) (only
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`original applications and eflicacy supplements that require a manufacturing
`
`
`
`
`
`
`
`facility inspection(e.g., new strength, manufacturing process, or manufacturing
`Sitechange)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Acceptable
`
`
`Re-evaluation date: n/a
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`6 Do not include Master File (MF) reviews or communications to MF holders. However, these documents should be made available
`
`
`
`upon signatory request.
`
`
`
`Reference ID: 3942163
`Reference ID: 3942163
`
`

`

`NDA 208026
`
`
`
`Page 7
`
`
`
`
`Day of Approval Act1v1t1es
`oz. For all 505(b)(2) applications:
`
`
`
`
`
`0
`Check Orange Book for newly listed patents and/or exclusivity (including
`
`
`
`
`
`
`
`
`
`
`
`
`pediatric exclusivity)
`
`
`
`
`
`0
`
`
`
`
`Finalize 505(b)(2) assessment
`
`
`
`
`
`O
`9.0
`
`
`
`
`'2‘
`
`
`
`
`D No Changes
`
`
`
`
`ggzegjpgelnotjexclusmty (Notify
`
`
`
`
`
`
`
`
`
`|:| Done
`
`
`
`
`
`
`(Send email to CDER 0ND 10)
`
`
`1:] Done
`
`
`
`El Done
`
`
`
`El Done
`
`
`
`Done
`
`
`
`
`'2] Done
`
`
`
`IX Done
`
`
`
`‘
`
`
`
`
`
`
`
`
`
`
`
`
`
`For Breakthrough Therapy (BT) Designated drugs:
`
`
`
`
`
`
`
`0 Notify the CDER BT Program Manager
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'3 For products that need to be added to the flush list (generally opioids): Flush List
`
`
`
`
`
`
`
`
`
`
`0 Notify the Division of Online Communications, Office of Communications
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'1‘ Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`If an FDA communication will issue, notify Press Office of approval action after
`
`
`
`
`
`
`
`
`
`confirming that applicant received courtesy copy of approval letter
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'2' Ensure that proprietary name, if any, and established name are listed in the
`.
`.
`.
`.
`.
`
`
`
`
`
`
`
`
`
`
`Application Product Names section of DARRTS, and that the proprletary name 1s
`identified as the “ referred” name
`
`
`
`
`
`‘1. Ensure Pediatric Record is accurate
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'3' Send approval email within one business day to CDER-APPROVALS
`
`
`