CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`206073Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 206073
`
`SUPPL # N/A
`
`HFD # N/A
`
`Trade Name Glyxambi
`
`Generic Name empagliflozin and linagliptin
`
`Applicant Name Boehringer Ingelheim
`
`
`
`Approval Date, If Known January 30, 2015
`
`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)
`
`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.
`
`N/A
`
`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:
`
`N/A
`
`
`
`Reference ID: 3689708
`
`Page 1
`
`

`

`d) Did the applicant request exclusivity?
`
`YES
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`3
`
`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
`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
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`Reference ID: 3689708
`
`Page 2
`
`

`

`N/A
`
`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# 201280
`NDA# 201281
`NDA# 204629
`
`Linagliptin tablets
`Linagliptin/metformin HCl tablets
`Empagliflozin 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."
`
`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.
`
`Reference ID: 3689708
`
`Page 3
`
`

`

`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:
`
`
`
`N/A
`
`(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:
`
`N/A
`
`Reference ID: 3689708
`
`Page 4
`
`

`

`(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:
`
`1275.1 - A phase III randomized, double-blind, parallel group study to evaluate the
`efficacy and safety of once daily oral administration of BI 10773 25 mg/linagliptin 5 mg
`and BI 10773 10 mg/linagliptin 5 mg Fixed Dose Combination tablets compared with the
`individual components (BI 10773 25 mg, BI 10773 10 mg, and linagliptin 5 mg) for 52
`weeks in treatment naïve and metformin treated patients with type 2 diabetes mellitus with
`insufficient glycaemic control
`
`
`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:
`
`N/A
`
`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
`
`YES
`
`NO
`
`Reference ID: 3689708
`
`Page 5
`
`

`

`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`N/A
`
`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"):
`
`1275.1 - A phase III randomized, double-blind, parallel group study to evaluate the
`efficacy and safety of once daily oral administration of BI 10773 25 mg/linagliptin 5 mg
`and BI 10773 10 mg/linagliptin 5 mg Fixed Dose Combination tablets compared with the
`individual components (BI 10773 25 mg, BI 10773 10 mg, and linagliptin 5 mg) for 52
`weeks in treatment naïve and metformin treated patients with type 2 diabetes mellitus with
`insufficient glycaemic control
`
`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
`!
`
`
`
`Investigation #1
`
`IND # 108388
`
`YES
`
`
`
`
`
`(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?
`
`Reference ID: 3689708
`
`Page 6
`
`

`

`!!
`
`
`! 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:
`
`N/A
`
`=================================================================
`
`Name of person completing form: Callie Cappel-Lynch
`Title: Regulatory Project Manager
`Date: 1/20/2015
`
`
`Name of Office/Division Director signing form: William Chong (on behalf of Jean-Marc Guettier)
`Title: Clinical Team Leader, Acting
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3689708
`
`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/
`----------------------------------------------------
`
`CALLIE C CAPPEL-LYNCH
`01/20/2015
`
`WILLIAM H CHONG
`01/20/2015
`Signing on behalf of Dr. Jean-Marc Guettier
`
`Reference ID: 3689708
`
`

`

`ACTION PACKAGE CHECKLlST
`
`
`APPLICATION INFORMATION1
`
`
`
`
`NDA # 206073
`
`NDA Supplement # N/A
`
`lfNDA, Efficacy Supplement Type: N/A
`(an action package is not requiredfor SE8 or SE9 supplements)
`
`‘l
`
`Proprietary Name: Glyxambi
`Applicant: Boehringer Ingelheim
`Established/Proper Name: empagliflozin and linagliptin
`Agent for Applicant (if applicable): N/A
`Dosage Form:
`tablets
`RPM: Callie Cappel-Lynch
`‘ Division. Metabolism and Endocrinology Products
`
`For ALL__505§b)—12) applications, two months prior to EVERY action:
`-
`_—“‘
`
`505(b)(l)
`I:I 505(b)(2)
`El 505(b)(1) Cl 505099)
`
`NDA Application Type:
`Efficacy Supplement:
`
`BLA Application Type:
`Efficacy Supplement:
`
`[:I 351(k) El 351(a)
`I] 351(k)
`[:l 351(a)
`
`
`
`6
`
`Rev'ew the informaton in the 505(b)(2) Assessment and submit
`the draft2 to CDER 0ND 10 for clearance.
`
`0
`
`Check Orange Book for newly listed patents and/0r
`exclusivity (including pediatric exclusivity)
`
`[I No changes
`[I New patent/exclusivity (notify CDER 0ND 10)
`Date of check:
`
`l Note: prediatric exclusivity has been granted or the pediatric
`1 information in the labeling of the listed drug changed, determine whether
`1 pediatric information needs to be added to or deletedfrom the labeling of
`this drug;
`
`
`
`
`
`
`
`0
`Proposed action
`0 User Fee Goal Date1s January 30 201
`0
`Previous actions (specifi/ type and datefor each“action taken)"
`‘
`
`If accelerated apprOval or approval based on efficacy studies1n animals, were promotional
`materials received?
`
`’3‘
`
`’ Actions
`
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions, see
`http_://www. fdagov/downloads/D1uvs/Guidarz ceCompiianceR aguiatorvln.‘br1nation,’Gui:la
`11ces/ucm069965pd1‘). If not submitted, explain
`
`
`0
`
`so Application Characteristics3
`
`
`
`
`
`
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`the documents to be included1n the Action Package.
`2 For resubmissions, 505(b)(2) applications must be cleared before the action but it is not necessary to 1esubmit the draft 505(b)(2)
`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e. g. , new listed drug. patent certification
`revised).
`\nswer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`pplement, then the questions should be answered in relation to that supplement not in relation to the original NDA or BLA. For
`example, If the applicationis a pending BLA supplement then a new RMS-BLA Product Information Sheetf0; TBP must be
`completed.
`
`Version: 6/23/2014
`
`Reference ID: 3699635
`Reference ID: 3699635
`
`

`

`NDA #206073
`
`Page 2
`
`
`
`
`
`
`[3 Priority
`X] Standard
`Review priority:
`I
`Chemical classification (new NDAs only):
`(confirm chemical classification at time of approval)
`
`D Fast Track
`E] Rolling Review _
`[I Orphan drug designation
`El Breakthrough Therapy designation
`
`[:1 Rx-to—OTC full switch
`El Rx—to—OTC partial switch
`E] Direct-to-OTC
`
`NDAs: Subpart H
`CI Accelerated approval (21 CFR 314.510)
`I] Restricted distribution (21 CFR 314.520)
`Subpart I
`[:I Approval based on animal studies
`
`BLAs: SubpartE
`I:I Accelerated approval (21 CFR 601.41)
`D Restricted distribution (.21 CFR 601.42)
`Subpart 1-1
`El Approval based on animal studies
`
`EDD
`
`Submitted in response to a PMR
`Submitted in response to a PMC
`Submitted in response to a Pediatric Written Request
`
`REMS:
`
`lVIedGuide
`Communication Plan
`ETASU
`MedGuide w/o REMS
`
`DEUCE
`
`
`
`
`
`
`
`
`
`
`
`REMS not requn'ed
`
`
` Comments: None
`
` BLAs only:
`
`Is the product subject to official FDA lot release per 21 CPR 610.2
`(approvals only)
`
`v Public communications (approvals only)
`
`0
`
`Office of Executive Programs (OEP) liaison has been notified of action
`
`0
`
`Indicate what types (if any) of information were issued
`
`o
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5—year
`NCE, 3-year, pediatric exclusivity)?
`If so, specify the type
`
`0
`
`° Patent Information (NDAs only)
`
`0
`
`
`
`
`
`
`
`v Exclusivity
`
`
`
`
`
`
`: E Yes L] No
`: l2 None
`5 g FDA Press Release
`T L_i FDA Talk Paper
`; 1.: CDER Q&As
`
`K4 No
`
`C] Yes
`
`
`
`
`
`0
`
`Patent Information:
`
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`
`El Verified
`[:1 Not applicable because drug is
`an old antibiotic.
`
`CONTENTS OF ACTION PACKAGE
`
`
`
` Officer/Employee List
`
`List of officers/employees who participated in the decision to approve this application and E Included
`
`
`Included
`
`
`
`Documentation of consent/non-consent by officers/employees
`
`Reference ID: 3699635
`Reference ID: 3699635
`
`Version: 1/5/2015
`
`

`

`NDA #206073
`
`Page 3
`
`Acti0n(s) and date(s) AP January
`' Copies of all action letters (including approval letter withfinal labeling) 3 0 201 5
`
`
`
`Action Letters
`
`
`
`Labeling
`
`
`
`
`
`K4 Included
`
`
`
`
`ME.......l ncluded....................................................................................................
`
`
`
`K4 Medication Guide
`E Patient Package Insert
`L Instructions for Use
`E] Device Labeling
`
`I: None
`
`Included
`
`!
`
`
`1
`
`‘
`1
`3
`
`|'
`
`i
`
`
`'
`‘
`‘u
`
`T » i“
`X ’nCldde
`
`d
`
`‘
`t
`. 2
`It??? 3 28::
`y ’
`
`
`0
`
`Original applicant-proposed labeling
`
`_
`'3' Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirst page of each piece)
`
`0 Most-recent draft labeling (ifit is division-proposed labeling, it should be in
`track-changes format)
`
`0
`
`Original applicant—proposed labeling
`
`9% L
`o
`
`abels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirst page of each submission)
`o Most-recent draft labeling
`
`v Proprietary Name
`0
`Acceptability/non—acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s)
`
`Labeling reviews (indicate dates ofreviews)
`
`0 v
`
`
`
`
`
`
`
`RPM: E None
`‘ DMEPA: June 16 and 19,2014
`3 DMPP/PLT (DRlSK):
`January 8, 2015
`g CPDP: January 7, 2015
`SEALD: K1 None
`3 CSS: IX} None
`
`Administrative / Regulatory Documents
`
`V March 27’ 2014
`’21 Not a (0X2)
`
`[XI
`
`Included
`
`'2‘ RPM Filing Review4/Memo of Filing Meeting (indicate date ofeach review)
`v All NDA 505(b)(2) Actlons: Date each action cleared by 505(b)(2) Clearance Committee
`
`
`6' NDAs only: Exclusivity Summary (signed by Division Director)
`
`Application Integrity Policy (AlP) Status and Related Documents
`http://www.fda.Gov/lCECl/EnforcementActions/ApplicationlnteorityPo’,icy/defaulthtin
`
`0 v
`
`
`
`
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Version: 1/5/2015
`
`Reference ID: 3699635
`Reference ID: 3699635
`
`
`
`

`

`NDA #206073
`
`Page 4
`
`o
`
`This application15 on the AIP
`o
`If yes, Center Director’s Exception For Review memo (indicate date)
`‘ZL‘
`l ‘
`IA
`.
`.
`2». yes, \1L eleai‘ance for approval (Inc/[cafe date a clearance
`o
`.
`"
`.
`‘
`‘
`f
`
`commumcalmn}
`
`' — v
`
`g No
`
`.
`—-
`L] Not an AP action
`
`'1' Pediatrics (approvals oniy,‘
`
`0
`Date reviewed by PeRC December3 2014
`If PeRC review not necessary, explain:
`
`i
`
`'3’ Outgoing communications: letters, emails. and "faxes considered important to include in
`the action package by the reviewing office/division’tea.g. , clinical SPA letters, RT F letter,
`etc.) (do no! {news,, p1eviaz5 action [eIte/s as these {.7e located elsewhe/e m package)
`
`
`
`‘3‘
`
`Internal documents: memoranda, telecons, emails, and other documents considered
`important to include it; the acticn package by the reviewing office/division (e.g.,
`Regulatory Briefing minutes, Medical Policy Council meeting minutes)
`
`'2‘ Minutes "of Vleetinos
`
`‘ January 27, 2015
`January 14, 2015
`1 December 8, 2014
`5 October 10, 2014
`I August 27, 2014
`' July 10,2014
`June 10,2014
`June 4, 2014
`3 April 11, 2014
`:Apri18,2014
`. March 31, 2014
`1 March 27,2014
`:__February 1 l, 2014
`1, November 19,2014 — PeRC
`‘_
`template
`September 1 1, 2014 - memo of
`‘ OSl tcon
`
`
`
`
`
`
`1
`
`
`Ifnot the inst revie‘v cycle, any end-of—re1iew meeting (indicate date ofmlg) . X N/A or no mtg
`“ Meeting cancelled at sponsor
`request, letter included—
`preliminary comments sent
`__ 7/29/13 a
`
`
`
`
`‘
`
`
`
`
`
`
`
`
`
`
`Pre—NDA/BLA meeting (indicate daze qf‘irzrgj)
`
`EOP2 meeting (indicate date afmrg)
`
`o Mid-cycle Communication {indicate aaz‘e ofmtg)
`
`-
`
`0
`
`o
`
`o
`
`0
`
`Late-cycle Meeting (indicate dale ofmtg)
`
`Other milestone meetings (e.g., EOP2a, CMC pilots) (indicate dates ofmtgs)
`
`0.. Advisory Committee Meeting(s)
`
`o
`
`Date(s) of Meeting(s)
`
`0? Office Director Decisional Memo (indicate dazefor each review)
`
`
`
`Decisional and Summary Memos
`
`Cross-Discipline Team Leader Review (indicate dare/0r 6610/? review)
`
`PMR/PMC Development Templates (indicate total number)
`
`.................................................................................................................................................................................................................................................................................................................................................................................................................IX] None SeeCDTLRev1ew
`.........................D‘V‘s‘OnD‘reCtorsummar..Rev’ew(’”da’edatefo’emMW)
`datedJanuary292015
`
`Clinical
`I
`
`Version: 1/5/2015
`
`Reference ID: 3699635
`Reference ID: 3699635
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`None
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`January 29, 2015
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`X None
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`NDA #206073
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`g No separate rev1ew
`SeeCDTLIeVIewforfinalrev1ew
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`0
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`Social scientist review(s) (if OTC drug) (indicate date for each review)
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`'2‘ Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`If no financial disclosure information was required, check here [:I and include a
`review/memo explaining why not (indicate date ofreview/memo)
`v Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date of each review)
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`’1‘ Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of
`each review)
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`'3 Risk Management
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`REMS Documents and REMS Supporting Document (indicate date(s) 0f
`submissi0n(s))
`REMS Memo(s) and letter(s) (indicate a’aze(s))
`Risk management review(s) and recommendations (including those by OSE and
`CSS) (indicate dale ofeach review and indicate location/date ifincorporated
`into another review)
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`o
`0
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`IX] None
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`See CDTL review dated January
`29,2015 (pg. 139-140)
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`X None
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`1 El N/A
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`l January 2, 2015
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`Clinical Microbiology
`None
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`’ Clinical Microbiology Team Leader Review(s) (indicate date for each review)
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`1 October 29, 2014
`. 8:12:33: 38:: (2)
`081 Clinical Inspection Review Summary(ies) (include copies ofOS] letters to
`§ October 15, 2014
`ll’lVeSllgatOI‘S)
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`f October 6, 2014
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`Clinical Microbiology Review(s) (indicate datefor each review)
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`?_
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`'3 Statistical Division Director Review(s) (indicate datefor each review)
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`Statistical Team Lead R
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` Clinical Pharmacology
`E] None
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`Clinical Pharmacology review(s) (ind. /. 2 aafefer each review)
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`'_April 8; 2014
`C'itc'oer .
`2014
`
`
`081 Clinical Pharmacology Inspection Review Summary (include copies ofOS] letters)
`1 901 4
`A oril 1
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`Biostatistics
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`E] None
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`Reference ID: 3699635
`Reference ID: 3699635
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`Version: 1/5/2015
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`NDA #206073
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`1 March 27, 2014
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`0:. Statistical review(s) of carcinogenicity studies (indicate datefor each review)
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`E No carc
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`-
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`'3‘ ECAC/CAC report/memo 0.1 sheeting
`'3’ OS] Nonclinical Inspection Review Summary (incluae copies ofOSl letters)
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`I
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`[3 None
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`1 E N ne
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`E None requested
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`'2' Product Quality Discipline R
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`C’NDQA’(‘E’P Di11s5t»:1-‘31re:to1 1’31 1.v\(s)Indicate 1'rtvf01 each 1ev1cw)
`o
`0
`Branch Chief/Team Leader Review(s)(indicate datefor each review)
`
`
`‘»
`No separate review
`1
`No separate review
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`‘ October 15, 2014
`September 16, 2014
` 0
`Product quality review/(s) including ONDQA biopharmaceutics reviews (indicate
`August 19, 2014
`datefor each review)
`March 20, 2014
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`' March 19, 2014
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`O
`9
`. Microbiology Reviews
`E NDAs: Microbiology reviews (sterility & pyrogenicity) (OPS/NDMS) (indicate
`date of each review)
`E] BLAs: Sterility assurance, 111icrobiology, faci1ities reviews
`(OMPQ/MAPCB/BMT/ (indicate date ofeach review)
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`=
`1 August 8, 2014
`1 February 25, 2014
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`Reviews by other disciplines/divisions/Centers requested by CMC/quality reviewer
`(indicate date ofeach review)
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`'_—":_"'_"'"'—_——_—._.___"—m—"mA—"T—m''''_1‘_-_____
`.
`.
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`%‘ Env1r0nmental Ass 35nent’check one)(or1gmal and supplement
`applications)
`1
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`E Categ01ical Exclusion (indicate ieview date)(all original app/Icanons and
`all efficacy
`[Jo/2111111115 that couldIncrease the patientpopulazion)
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`‘18/19/14 (pg. 67--68)
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`1, See product quality review dated
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`[:1 Review & Environmental Impact Statement (indicate date of each review)
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`v Facilities Review/lnspection
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`p
`NDAs: Facilities inspections (include EER printout or EER Summ y
`only; do N_OT include EER Detailed Report; date completed must be within 2
`years of action date) (only original NDAS and supplements that include a new
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`I:I BLAs: TB-EER (date of most recent TB-EER must be within 30 days of action
`date) (original and supplemental BLAS)
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`Date completed: July 22, 2014
`Acceptable
`[:1 Withhold recommendation
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`N/A
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`5 i.e., a new facility or a change in the facility, or a change in the manufacturing process in a way that impacts the Quality
`Management Systems of the facility.
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`Version: 1/5/2015
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`Reference ID: 3699635
`Reference ID: 3699635
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`P. 3'
`{:1
`‘
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`Pharm/tox review/(s). 1r uding referenced 1ND reviews (indicate datefor each
`review)
`'3 Review(s) by other uisciplines.divisions/Centers requested by RT reviewer (indicate date
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`for each review)
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`NDA #206073
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`Y. NDAs: Methods Validation (check box only, do not include documents)
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`El Completed
`I: Requested
`D Not yet requested
`Not needed (per review dated
`8/19/14 pg. 6)
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`Reference ID: 3699635
`Reference ID: 3699635
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`Version: 1/5/2015
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`NDA #206073
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`Page 8
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`Day of Approval Activities
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`I
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`.
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`'3' For all 505(b)(2) applications:
`0 Check Orange Book for newly listed patents and/or exclusivity (including
`‘ N/A
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`pediatric exclusivny)
`J_
`0
`Finalize 505(b)(2) assessment
`N/A
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`I\I/A
`'3‘ For Breakthrough Therapy(BT) Designated drugs:
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`0 Notify the CDER BT Program Manager
`Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`X Done
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` email
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`‘3‘
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`6°
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`If an FDA communication will issue, notify Press Office of approval action afier
`N/A
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`confirming that applicant received courtesy copy of approval letter
`W D
`0:. Ensure that proprietary name, if any, and established name are listed in the
`Application Product Names section of DARRTS, and that the proprietary name is
`‘ one
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`identified as the “preferred” name
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`v Ensure Pediatric Record is accurate
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`[2 Done
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`E Done
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`v Send approval email Within one busmess day to CDER-APPROVALS
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`Reference ID: 3699635
`Reference ID: 3699635
`
`Version: 1/5/2015
`
`

`

`From:
`To:
`Subject:
`Date:
`Attachments:
`
`CappelLynch, Callie
`"chung.lee-sogaard@boehringer-ingelheim.com"
`RE: NDA 206073 empagliflozin + linagliptin FDC
`Tuesday, January 27, 2015 4:46:00 PM
`Empagliflozin Linagliptin US PI FDA Comments 1.27.15.docx
`image001.png
`
`Hi Chung,
`
`Please see the attached PI for NDA 206073 with FDA comments. If you have any questions, please
`contact me ASAP. We request that you review our comments and provide revised labeling by COB
`tomorrow, Wednesday, January 28, 2015.
`
`Thanks,
`Callie
`
`From: chung.lee-sogaard@boehringer-ingelheim.com [mailto:chung.lee-sogaard@boehringer-
`ingelheim.com]
`Sent: Tuesday, January 27, 2015 10:21 AM
`To: CappelLynch, Callie
`Subject: RE: NDA 206073 empagliflozin + linagliptin FDC
`
`Dear Callie,
`
`Thanks again. As you can imagine, we are looking forward to the next round of comments!
`
`Chung.
`
`Chung Lee-Søgaard, Ph.D.
`Drug Regulatory Affairs
`Boehringer-Ingelheim Pharmaceuticals, Inc.
`Tel: 1-203-798-4224
`Fax: 1-203-791-6262
`Email: chung.lee-sogaard@boehringer-ingelheim.com
`
`From: CappelLynch, Callie [mailto:Callie.CappelLynch@fda.hhs.gov]
`Sent: Tuesday, January 27, 2015 10:16 AM
`To: Lee-Sogaard,Dr.,Chung (DRA) BIP-US-R
`Subject: RE: NDA 206073 empagliflozin + linagliptin FDC
`
`Hi Chung,
`
` I
`
` hope to have labeling to you at some point today. If this changes, I’ll let you know. As stated
`before, senior management has been involved in this review. At this time, I do not believe we have
`any comment on the most recent carton/container labels.
`
`Thanks,
`Callie
`
`
`Reference ID: 3693297
`
`

`

`From: chung.lee-sogaard@boehringer-ingelheim.com [mailto:chung.lee-sogaard@boehringer-
`ingelheim.com]
`Sent: Friday, January 23, 2015 8:14 AM
`To: CappelLynch, Callie
`Subject: NDA 206073 empagliflozin + linagliptin FDC
`
`Dear Callie,
`
` I
`
` was wondering if there might be any update regarding review of the draft labeling. It would be
`really helpful to have an idea approximately when we can expect the next round of comments and
`whether senior management will be involved in the review. Also, would you have any update
`regarding carton and container labeling?
`
`Thank you in advance.
`Chung.
`
`
`
`Chung Lee-Søgaard, Ph.D.
`Associate Director, Regulatory Affairs
`Boehringer Ingelheim Pharmaceuticals, Inc.
`Ridgefield, CT
`P: 203 798 4224 :: C:
`chung.lee-sogaard@boehringer-ingelheim.com
`
`
`
`
`
`
`Reference ID: 3693297
`
`21 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following
`this page
`
`(b) (6)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`CALLIE C CAPPEL-LYNCH
`01/27/2015
`
`Reference ID: 3693297
`
`

`

`From:
`To:
`Subject:
`Date:
`Attachments:
`
`CappelLynch, Callie
`"chung.lee-sogaard@boehringer-ingelheim.com"
`RE: NDA 206073 Labeling Comments
`Wednesday, January 14, 2015 5:54:00 PM
`Empagliflozin Linagliptin US PI BI Response to FDA 17DEC2014 (3).docx
`
`Hi Chung,
`
`Please see the attached label with FDA comments. Please review and provide revised labeling by
`COB Monday January 19, 2015. If you have any questions, please contact me.
`
`Thanks,
`Callie
`
`From: chung.lee-sogaard@boehringer-ingelheim.com [mailto:chung.lee-sogaard@boehringer-
`ingelheim.com]
`Sent: Tuesday, January 13, 2015 3:47 PM
`To: CappelLynch, Callie
`Subject: RE: NDA 206073 Labeling Comments
`
`Dear Callie
`
` was wondering if we can still expect labeling comments back this week?
`
` I
`
`
`Thank you!
`Chung.
`
`
`Chung Lee-Søga