CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`205395Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 205395
`
`SUPPL #
`
`HFD # 530 (DAVP)
`
`Trade Name: PREZCOBIX
`
`Generic Name: darunavir and cobicistat
`
`Applicant Name: Janssen Products, LP
`
`Approval Date, If Known: January 29, 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.
`
`The sponsor submitted BA and BE study data in healthy volunteers, and data from a single-
`arm, open label study in patients with HIV-1 infection. The BA study, TMC114IFD1001,
`evaluated two different formulations of darunavir/cobicistat FDC formulations compared to
`darunavir co-administered with ritonavir. The BE study, TMC114FD1003, evaluated the BE
`of the darunavir/cobicistat FDC tablet compared to the individual cobicistat and darunavir
`tablets. The BE data was considered pivotal and required for approval.
`The open label study, GS-US-216-0130, evaluating the safety and efficacy of the
`darunavir/cobicistat FDC was reviewed to support the safety of the product, but was not
`needed for approval.
`
`Reference ID: 3694158
`
`Page 1
`
`

`

`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?
`
`YES
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`3 years
`
`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?
`
`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: 3694158
`
`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# 21976
`NDA# 202895
`NDA# 203100
`
`Prezista (darunavir), Tablet, Film-coated
`Prezista (darunavir), Suspension
`Stribild
`(elvitegravir, cobicistat, emtricitabine,
`disoproxil fuamrate), Tablet
`
`tenofivir
`
`NDA# 203094
`
`Tybost (cobicistat), Tablet
`
`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: 3694158
`
`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:
`
`Cobicistat co-administered with darunavir was approved in September 2014. The only data
`essential to the approval of the fixed-dose formulation of darunavir and cobicistat is the
`bioequivalence study, TMC1141FD1003.
`
`(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: 3694158
`
`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 the
`effectiveness of a previously approved drug product?
`
`Reference ID: 3694158
`
`Page 5
`
`

`

`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
`
`YES
`
`Investigation #2
`
`IND #
`
`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?
`
`Investigation
`
`!
`
`Reference ID: 3694158
`
`!
`
`Page 6
`
`

`

`! NO
`! Explain:
`
`!!
`
`! NO
`! Explain:
`
`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: Nina Mani, PhD, MPH
`Title: Regulatory Project Manager
`Date: December 24, 2014
`
`Name of Office/Division Director signing form: Jeffrey Murray, MD MPH
`Title: Deputy Division Director
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3694158
`
`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/
`----------------------------------------------------
`NINA MANI
`01/29/2015
`
`JEFFREY S MURRAY
`01/29/2015
`
`Reference ID: 3694158
`
`

`

`ACTION PACKAGE CHECKLIST
`
`APPLICATION INFORMATION1
`
`NDA # 205395
`BLA #
`V
`
`NDA Supplement # 0
`BLA Supplement #
`
`If NDA, Efficacy Supplement Type: n/a
`(an action package is not requiredfor SE8 or SE9 supplements)
`
`
`
`Applicant: Janssen Products, LP
`Agent for Applicant (if applicable):
`
`Proprietary Name: Prezcobix
`Established/Proper Name: darunavir and cobicistat
`Dosage Form:
`Tablets, 800mg/ 1 5 0mg
`RPM: Nina Mani
`
`NDA Application Type:
`Efficacy Supplement:
`
`505(b)(l) E] 505(b)(2)
`1:! 505(b)(l) El 505(b)(2)
`
`BLA Application Type: D 351(k) D 351(3)
`Efficacy Supplement:
`El 351(k) D 351(a)
`
`Division: Antiviral Products
`
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
`.
`
`Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER 0ND 10 for clearance.
`o Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
`[:I 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 of the listed drug changed, determine whether
`pediatric information needs to be added to or deletedfrom the labeling of
`this drug.
`
`
`
`Proposed action
`0
`0 User Fee Goal Date is Januafl 31, 2015
`
`0
`
`Previous actions (specify type and datefor each action taken)
`
`
`
`O a
`
`t
`
`
`
`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
`ht.tp //www fda. gov/downloads/Drua=s/GuidanceComplianceRegulatoryInformation/Guida
`
`nces/ucm069965.d—p_i). If not submitted, explain—
`
`[I Received
`
`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)
`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
`revised).
`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA 0r BLA
`applement, 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: 6/23/2014
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`

`

`I:I Priority
`Standard
`Review priority:
`Type 4
`Chemical classification (new NDAs only):
`(confirm chemical classification at time ofapproval)
`
`El Fast Track
`I:] Rolling Review
`E] Orphan drug designation
`E] Breakthrough Therapy designation
`
`Rx-to-OTC full switch
`Rx-to-OTC partial switch
`Direct-to-OTC
`
`NDAs: SubpartH
`I] Accelerated approval (21 CFR 314.510)
`E] Restricted distribution (21 CFR 314.520)
`Subpart I
`[:I Approval based on animal studies
`
`BLAs: Subpart E
`El Accelerated approval (21 CFR 601.41)
`D Restricted distribution (21 CFR 601.42)
`Subpart H
`[3 Approval based on animal studies
`
`Submitted in response to a PMR
`Submitted in response to a PMC
`Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: El MedGuide
`[I Communication Plan
`E] ETASU
`El MedGuide w/o REMS
`IX] REMS not required
`
`‘3' BLAs only: Is the product subject to official FDA lot release per 21 CFR 610.2
`(approvals only)
`
`0
`
`0
`
`0
`
`o
`
`0
`
`Office of Executive Programs (OEP) liaison has been notified of action
`
`[:I Yes El No
`
`Indicate what types (if any) of information were issued
`
`El None
`El FDA Press Release
`El FDA Talk Paper
`[:1 CDER Q&As
`IZOther HIV List serve
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5--year
`NCE, 3——,year pediatric exclusivity)?
`If so, specify the type
`
`Patent Information:
`
`Verify that form FDA-3 542a was submitted for patents that claim the drug for
`which approval is sought.
`
`IZI Verified
`[I Not applicable because drug is
`an old antibiotic.
`
`
`
`_
`
`CONTENTS OF ACTION PACKAGE
`
`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 officers/employees
`
`v
`
`Included
`
`Included
`
`6 v
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`Version: 1/5/2015
`
`

`

`NDA/BLA #
`
`Page 3
`
`‘2' Copies of all action letters (including approval letter withfinal labeling)
`
`lA/ggifigigand date(s): AP and
`
`Action Letters
`
`»
`Labeling
`
`
`
`E Included
`
`
`..............................................................arackchangeSformat)
`
`
`- Original applicant-proposed labeling
`
`
`
`
`
`El Medication Guide
`
`Patient Package Insert
`
`
`
`v Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`[:I Instructions for Use
`submission/communication date at upper right offirst page ofeach piece)
`
`
`[:1 Device Labeling
`
`
`[3 None
`IX! Included
`- Most—recent draft labeling (if it is division-proposed labeling, it should be in
`
`track-changesformat)
` Original applicant—proposed labeling
`
`
`Labels (full color carton and immediate-container labels) (write
`
`submission/communication date on upper right offirst page of each submission)
`Most-recent draft labeling IE Included
`
`
`
`IX] Included
`
`“ Proprietary Name
`0
`Acceptability/non—acceptability 1etter(s) (indicate date(s)):
`0
`Review(s) (indicate date(s):
`
`5/27/2014
`5/20/2014
`
`Labeling reviews (indicate dates ofreviews)
`
`Administrative / Regulatory Documents
`
`RPM Filing Review/Memo of Filing Meeting (indicate date ofeach review)
`
`RPM: D 1/28/2015
`DMEPA: [I 11/6/2014;
`12/19/2014; 12/24/2014
`DMPP/PLT (DRISK):
`I] 1/5/2015
`OPDP: El 1/5/2015
`SEALD: 12 None
`CSS:
`None
`
`Other: IX] None
`
`5/30/2014
`
`IX] Not a (b)(2)
`
`
`
`
`
`All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`'3 NDAs only: Exclusivity Summary (signed by Division Director)
`
`Included
`
`v Application Integrity Policy (AIP) Status and Related Documents
`http://Www.fda.gov/ICECI/EnforcementActions/ApplicationIntegrityPolicy/default.htm
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Version: l/5/2015
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`

`

`o
`
`This application is on the AIP
`0
`If yes, Center Director’s Exception for Review memo (indicate date)
`
`El Yes X No
`
`0
`
`If yes, OC clearance for approval (indicate date ofclearance
`.
`,
`communzcatzon)
`
`[:I Not an AP action
`
`Pediatrics (approvals only)
`0 Date reviewed by PeRC December 3 2014
`
`If PeRC review not necessary, explain:
`
`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,
`
`
`etc.) (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)
`
`
`Minutes of Meetings
`
`-
`
`o
`
`If not the first review cycle, any end-of-review meeting (indicate date ofmtg)
`
`
`
`
`
`o
`
`o
`
`Pre—NDA/BLA meeting (indicate date ofmtg)
`
`EOP2 meeting (indicate date ofmtg)
`
`o Mid-cycle Communication (indicate date ofmtg)
`
`
`
`
`N/A or no mtg
`
`N0 mtg
`
`No mtg
`
`N/A
`
`Late-c-ycle Meeting (indicate date ofmtg)
`AN/A
`Other milestone meetings (e.g., EOP2a, CMC pilots) (indicate dates ofmtgs) _
`‘3‘ Advisory Committee Meeting(s)
`I No AC meeting
`
`
`
`0 Date(s) of Meeting(s)
`
`Decisional and Summary Memos
`
`Division Director Summary Review (indicate date for each review)
`
`Cross-Discipline Team Leader Review (indicate date for each review)
`
`PMR/PMC Development Templates (indicate total number)
`
`Clinical Reviews
`
`0..
`
`Socral screntlst rev1ew(s) (1f OTC drug) (Indicate date for each revzew)
`
`None
`
`Fmancral Disclosure rev1ews(s) or location/date 1f addressed In another rev1ew
`OR
`If no financial disclosure information was required, check here [:I and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`In Clinical Review/ 12/19/2014
`and 12/22/2014
`
`‘1' Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`El None
`
`12/15/2014
`
`Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of ® N/A
`each review)
`
`Version: 1/5/2015
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`Clinical Team Leader Review(s) (indicate date for each review)
`
`'d'
`
`Cl'
`
`‘
`
`l
`
`'
`
`d
`
`'
`
`1/2/2015
`
`Three (3)
`
`No separate review
`
`12/22/2014
`
`0
`
`0
`
`0v
`
`O
`
`

`

`NDA/BLA #
`
`Page 5
`
`‘3‘ Risk Management
`0
`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)
`
`0
`-
`
`None
`
`‘2‘ 081 Clinical Inspection Review Summary(ies) (include copies of 0S1 letters to
`investigators)
`
`
`None requested
`
`I:I None
`Clinical Microbiology
`
`
`
`
`‘1‘ Clinical Microbiology Team Leader Review(s) (indicate date for each review)
`No separate review
`
`
`Clinical Microbiology Review(s) (indicate date for each review)
`
`El None
`
`12/22/2014
`
`.
`
`Biostatistics
`
`None
`
`,
`
`‘1‘ Statistical Division Director Review(s) (indicate datefor each review)
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each review)
`
`
`
`
`[:I No separate review
`
`
`t
`D N
`
`
`I] None
`
`
`
`
`
`
`
`
`'
`
`Clinical Pharmacology
`
`E] None
`
`‘2‘ Clinical Pharmacology Division Director Review(s) (indicate date for each review)
`
`
`
`
`
`Clinical Pharmacology Team Leader Review(s) (indicate date for each review)
`_______________ChnlcalPharmacologyreVlew(s)(Indlcatedateforeachrewew)
`
`
`‘3‘ 081 Clinical Pharmacology Inspection Review Summary (include copies of0S] letters)
`Nonclinical
`[:I None
`
`No separate review
`
`No separate review
`DNon612/23/2014
`[1:21/51/i%ri:requested
`
`
`
`Pharmacology/Toxicology Discipline Reviews
`IE No separate review
`I
`ADP/T Review(s) (indicate datefor each review)
`.............................................Supemsogkewéwa)(mdlcatedateforea—chrewew)a" Noseparaterewew
`"HPharm/htopl—revwwé),includmgreferencedINDrev1ews(indicatedateforeach.........................................................................................................................................................
`|'_‘| None
`
`12/24/2014 review)
`
`
`
`‘2‘ Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`for each review)
`
`IX] None
`
`‘3‘ Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`No carc
`
`.‘.
`.
`
`-
`ECAC/CAC report/memo of meetmg
`
`None
`Included in P/T review, page
`
`‘t‘ 081 Nonclinical Inspection Review Summary (include copies of 051 letters)
`
`None requested
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`Version: 1/5/2015
`
`

`

`NDA/BLA #
`
`Page 6
`
`Product Quality
`1:] None
`
`Product Quality Discipline Reviews
` X] No se arate review
`
`
`
`
`
`Branch Chief/Team Leader Rev1ew(s) (indicate datefor each rev1ew)
`g No separate rev1ew
`E] None
`
`
`Product quality review(s) including ONDQA biopharmaceutics reviews (indicate
`Chemistry: 12/16/2014
`datefor each review)
`
`Biopharmaceutics: 12/5/2014
`
`I:I Not needed
`
`
`Microbiology Reviews
`Assessment of Microbial Limits:
`
`I:I NDAs: Microbiology reviews (sterility & pyrogenicity) (OPS/NDMS) (indicate
`7/ 1 6/ 20 1 4
`
`date ofeach review)
`
`I] BLAs: Sterility assurance, microbiology, facilities reviews
`(OMPQ/MAPCB/BMT) (indicate date ofeach review)
`
`
`
`XI Review & FONSI (indicate date of review)
`
`12/ 17/2014
`
`I:I Review & Environmental Impact Statement (indicate date ofeach review)
`
`
`
`Reviews by other disciplines/divisions/Centers requested by CMC/quality reviewer
`Kl None
`’
`(indicate date ofeach review)
`
`.‘ Environmental Assessment (check one) (original and supplemental applications)
`
`
`I] Categorical Exclusion (indicate review date)(all original applications and
`all efi‘icacy supplements that could increase the patient population)
`
`
`
`Facilities Review/Inspection
`
`
`
`IE NDAs: Facilities inspections (include EER printout or EER Summary Report
`
`only; do NOT include EER Detailed Report; date completed must be within 2
`
`years of action date) (only original NDAs and supplements that include a new
`
`[:I BLAs: TB-EER (date of most recent TB—EER must be within 30 days of action
`
`date) (original and supplemental BLAs)
`
`Date completed: 9/4/2014
`fi Acceptable (In Chemistry
`Review)
`E] Withhold recommendation
`
`Date completed:
`E xigblzlfecommendation
`
`
`El Completed
`
`
`El Requested
`
`NDAs: Methods Validation (check box only, do not include documents)
`El Not yet requested
`
`IXI Not needed (per review)
`
`
`0 v
`
`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.
`
`Version: 1/5/2015
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`

`

`NDA/BLA #
`
`Page 7
`
`Day of Approval Activities
`
`
`
`
`'3' For all 505(b)(2) applications:
`
`
`0 Check Orange Book for newly listed patents and/or exclusivity (including
`
`
`pediatric exclusivity)
`Finalize 505(b)(2) assessment
`
`0
`
`‘3' For Breakthrough Therapy(BT) Designated drugs:
`0 Notify the CDER BT Program Manager
`’3' Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
`
`‘1‘
`
`If an FDA communication will issue, notify Press Office of approval action after
`confirming that applicant received courtesy copy of approval letter
`
`1:] No changes
`[I New patent/exclusivity (Notzfi)
`CDER 0ND 10)
`
`D Done
`
`[I Done
`(Send email to CDER 0ND 10)
`I:I Done
`
`[:I Done
`
`’2‘ 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 D Done
`identified as the “ referred” name
`0:0 Ensure Pediatric Record is accurate
`
`D Done
`
`'2' Send approval email within one business day to CDER-APPROVALS
`
`[I Done
`
`
`
`
`
`Reference ID: 3699643
`Reference ID: 3699643
`
`Version: 1/5/2015
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Mani, Nina
`"Gerry, Karen [JRDCA]"
`RE: NDA 205395- labeling comment
`Tuesday, January 27, 2015 4:33:00 PM
`
`Hi Karen.
`
`In Table 2 of the USPI, the sedative/hypnotics medications that are listed should not be spaced out
`(buspirone, diazepam, etc, parenterally administered midalzolam and zoldipem). Please follow the
`spacing in the Word version since it appears that conversion to PDF messes up the spacing.
`
`Thanks,
`Nina
`From: Gerry, Karen [JRDCA] [mailto:kgerry@its.jnj.com]
`Sent: Tuesday, January 27, 2015 2:55 PM
`To: Mani, Nina
`Subject: RE: NDA 205395
`
`Hi Nina,
`
`Janssen acknowledges receipt of the appended NDA 205395 labeling comments from the Division.
`
`Kind regards,
`
`Karen
`
`
`
`
`Reference ID: 3693282
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`NINA MANI
`01/27/2015
`
`Reference ID: 3693282
`
`

`

`From:
`To:
`Subject:
`Date:
`Attachments:
`
`Mani, Nina
`Gerry, Karen [JRDCA] (kgerry@its.jnj.com)
`NDA 205395
`Tuesday, January 27, 2015 2:31:00 PM
`PREZCOBIX-annot-labeling-1 27 2015.pdf
`PREZCOBIX-annot-labeling-1 27 2015.docx
`
`Hi Karen:
`
`Kindly acknowledge receipt of the attached PDF and Word versions of the labeling for your
`comments.
`Please accept the changes you concur with, and only leave in changes/comments that are under
`negotiation.
`Please submit your response before COB, Wednesday, January 28, 2015.
`
`Regards,
`Nina
`
`Nina Mani, Ph.D., MPH
`Regulatory Project Manager
`FDA/CDER/OND/OAP
`Division of Antiviral Products
`10903 New Hampshire Avenue, Building 22
`Room 6317
`Silver Spring, MD 20993-0002
`Phone: 240-402-0333
`Fax: 301-796-9883
`e-mail: Nina.Mani@fda.hhs.gov
`
`NOTICE:
`Secure email between CDER and sponsors is useful for informal communications when
`confidential information may be included in the message (for example, trade secrets or
`patient information). If you have not already established secure email with the FDA and
`would like to set it up, send an email request to SecureEmail@fda.hhs.gov. Please note
`that secure email may not be used for formal regulatory submissions to applications (except
`for 7-day safety reports for INDs not in eCTD format).
`
`
`Reference ID: 3693106
`
`34 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`NINA MANI
`01/27/2015
`
`Reference ID: 3693106
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Mani, Nina
`"Gerry, Karen [JRDCA]"
`RE: NDA 205395: Labeling- Section 16
`Friday, January 23, 2015 2:12:00 PM
`
`If you do not concur please provide your reasoning.
`
`From: Mani, Nina
`Sent: Friday, January 23, 2015 2:07 PM
`To: 'Gerry, Karen [JRDCA]'
`Subject: RE: NDA 205395: Labeling- Section 16
`
`Hi Karen:
`
`We have the following additional edit in the Full Prescribing Information, Section 16 “How
`Supplied/Storage and Handling”:
`
`PREZCOBIX (darunavir and cobicistat) tablets, 800mg/150 mg, are supplied as pink,
`oval-shaped, film-coated tablets debossed with “800” on one side and “TG” on the other
`side.
`
`If you concur with this presentation please add it in the next iteration of the labeling that
`you submit.
`
`Kindly acknowledge receipt of this communication.
`
`
`Regards,
`Nina
`
`From: Gerry, Karen [JRDCA] [mailto:kgerry@its.jnj.com]
`Sent: Friday, January 23, 2015 9:09 AM
`To: Mani, Nina
`Subject: RE: NDA 205395: Labeling
`
`Good morning Nina,
`
`Janssen acknowledges receipt of the additional NDA 205395 labeling comments.
`
`Kind regards,
`
`Karen
`
`
`From: Mani, Nina [mailto:Nina.Mani@fda.hhs.gov]
`Sent: January-23-15 8:11 AM
`To: Gerry, Karen [JRDCA]
`
`Reference ID: 3691736
`
`

`

`Subject: NDA 205395: Labeling
`
`Hi Karen:
`
`Kindly acknowledge receipt of the attached labeling (Word and PDF) with our comments.
`When providing your response, please accept all edits we have agreement on. Only leave
`in edits/changes that are still being negotiated.
`Please provide your response by Monday, January 26, 2015.
`
`Regards,
`Nina
`
`Nina Mani, Ph.D., MPH
`Regulatory Project Manager
`FDA/CDER/OND/OAP
`Division of Antiviral Products
`10903 New Hampshire Avenue, Building 22
`Room 6317
`Silver Spring, MD 20993-0002
`Phone: 240-402-0333
`Fax: 301-796-9883
`e-mail: Nina.Mani@fda.hhs.gov
`
`NOTICE:
`Secure email between CDER and sponsors is useful for informal communications
`when confidential information may be included in the message (for example, trade
`secrets or patient information). If you have not already established secure email
`with the FDA and would like to set it up, send an email request to
`SecureEmail@fda.hhs.gov. Please note that secure