CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`205834Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 205834
`
`SUPPL #
`
`HFD #
`
`Trade Name HARVONI
`
`Generic Name ledipasvir/sofosbuvir fixed-dosed combination tablet
`
`Applicant Name Gilead Sciences
`
`
`
`Approval Date, If Known
`
`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.
`
`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: 3642186
`
`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?
`
`5 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
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`Reference ID: 3642186
`
`Page 2
`
`

`

`
`NDA#
`
`NDA#
`
`NDA#
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing 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# 204671
`NDA#
`NDA#
`
`Sovaldi (sofosbuvir)
`
`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.
`
`NDA 205834 contains ledipasvir, a new chemical entity, in combination with sofosbuvir, a
`previously approved active moiety. Under the Agency’s new interpretation described in the
`Agency’s Guidance for Industry, New Chemical Entity Exclusivity for Certain Fixed-
`Combination Drug Products, a drug substance is eligible for 5-year exclusivity, provided it meets
`the regulatory definition of new chemical entity, regardless of whether that drug substance is
`approved in a single-ingredient drug product or in a fixed-combination with another drug
`substance that contains no previously approved active moiety, or in a fixed-combination with
`another drug substance that contains a previously approved active moiety. This NDA is thus
`eligible for 5-year new chemical entity exclusivity pursuant to the new interpretation.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`Reference ID: 3642186
`
`Page 3
`
`

`

`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval of the application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`
`YES
`
`NO
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`YES
`
`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.
`
`Reference ID: 3642186
`
`Page 4
`
`

`

`YES
`
`NO
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`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.")
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`Reference ID: 3642186
`
`Page 5
`
`

`

`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`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?
`
`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?
`
`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:
`
`=================================================================
`
`
`Reference ID: 3642186
`
`Page 6
`
`

`

`Name of person completing form: Linda C. Onaga
`Title: Senior Regulatory Project Manager
`Date: October 10, 2014
`
`
`Name of Office/Division Director signing form: Debra Birnkrant
`Title: Director
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3642186
`
`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/
`----------------------------------------------------
`
`LINDA C ONAGA
`10/10/2014
`
`DEBRA B BIRNKRANT
`10/10/2014
`
`Reference ID: 3642186
`
`

`

`ACTION PACKAGE CHECKLIST
`
`NDA # 205 834
`BLA #
`
`NDA Supplement #
`BLA Supplement #
`
`IfNDA. Eflicacy Supplement Type:
`(an action package is not requiredfor SE8 or SE9 supplements)
`
`Proprietary Name: HARVONT
`Established/Proper Name:
`ledipasvir/sofosbuvir tablet
`Dosage Form:
`tablet
`
`Applicant: Gilead Sciences, Inc.
`Agent for Applicant (if applicable):
`
`RPM: Linda C. Onaga.1V[PH
`
`Division: Division of Ant1v1ral Products
`
`[:I 505(b)(2)
`IX] 505(b)(1)
`NDA Application Type:
`Efficacy Supplement: D 505(b)(1) D 505(b)(2)
`'
`.
`BLA APPl‘camn Type: E] 3510‘) D 3510‘)
`Efficacy supplement: D 3510‘) E] 351(3)
`
`. Review the information in the 505(b)(2) Assessment and submit
`the draft‘ to CDER 0ND 10 for clearance.
`Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
`For ALL 50519112} application; two months prior to EVERY action:
`
`
`
`I:] No changes
`|:] New patent/exclusivity (notifv 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.
`
`Proposed action
`User Fee Goal Date15 October 10.2014
`Previous actions (spectfi type and datefor each action taken)
`Ifaccelerated approval or approval based on efficacy studiesin animals. were promotional
`materials received?
`
`Note: Promotional materials to be used within 120 days afier approval must have been
`submitted (for exceptions. see
`llgpzflwww fda.gov/downloads/Drugs/GuidanceComplianceRegylatogInfonnation/Guida
`11ces/uc111069965pdfi). Ifnot submitted. explain
`
`Application Characteristics 3
`
`l The Application Information Section is (only) a checklist. The Contents ofAction 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 or BLA
`supplement. then the questions should be answered in relation to that supplement. not in relation to the original NDA or BLA. For
`example, if the application is a pending BLA supplement, then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version' 6/23/2014
`
`Reference ID: 3642299
`
`

`

`NDA 205834
`
`Page 2
`
`|:| Standard g Priority
`Review priority:
`Chemical classification (new NDAs only):
`(confirm chemical classification at time ofapproval)
`
`g Fast Track
`[I Rolling Review
`El Orphan drug designation
`[Z Breakthrough Therapy designation
`
`D Rx-to-OTC full switch
`E] Rx—to-OTC partial switch
`E] Direct-to-OTC
`
`NDAs: Subpart H
`[j Accelerated approval (21 CFR 314.510)
`I: Restricted distribution (21 CFR 314.520)
`SubpartI
`D Approval based on animal studies
`
`BLAs: Subpart E
`D Accelerated approval (21 CFR 601.41)
`I:] Restricted distribution (21 CFR 601.42)
`SubpartH
`|:] Approval based on animal studies
`
`I:I Submitted in response to a PMR
`I:I Submitted in response to a PMC
`El Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: D MedGuide
`D Communication Plan
`I:] ETASU
`D MedGuide w/o REMS
`El REMS not required
`
`02° BLAs only: Is the product subject to official FDA lot release per 21 CFR 610.2
`(approvals only)
`
`C] Yes
`
`[3 No
`
`°2° Public communications (apprm'als only)
`
`0 Office of Executive Programs (OEP) liaison has been notified of action
`
`IE Yes
`
`|:| No
`
`0
`
`Indicate what types (if any) of information were issued
`
`I: None
`IX] FDA Press Release
`El FDA Talk Paper
`D CDER Q&As
`[Z Other Listserv announcement
`
`°:° Exclusivity
`
`0
`
`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
`
`IX No
`
`C] Yes
`
`°3° Patent Information (NDAs only)
`
`0
`
`Patent Information:
`
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`
`% xiiifiedlicable because dru is
`“PP.
`.
`g
`an old antlblotic.
`
`
`
`
`
`IX] Included Documentation of consent/non-consent by officers/employees
`
`°3° List of officers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only)
`
`IX] Included
`
`Reference ID: 3642299
`
`Versiom 8/27/2014
`
`

`

`NDA 205834
`
`Page 3
`
`
`
`
`O
`0.. Copies of all action letters (including approval letter withfinal labeling)
`
`
`0
`0.. Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`
`Action(s) and date(s)
`October 10,2014
`
`
`
`0 Most recent draft labeling (yit is division-proposed labeling, it should be in
`track—changesformat)
`
`0 Original applicant-proposed labeling
`
`O
`0.. Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirstpage ofeach piece)
`
`
`
`D Medication Guide
`IX Patient Package Insert
`E] Instructions for Use
`El Device Labeling
`El None
`
`O0
`
`00
`
`.0 NDAs only: Exclusivity Summary (signed by Division Director)
`
`IX Included
`
`.0 Application Integrity Policy (AIP) Status and Related Documents
`IIQQIHWWW fda.govflCECI/EnforcementActions/ApplicationInteg'gPolicy/defaulthtm
`
`
`
`0 Applicant is on the AIP
`
`E] Yes E No
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Versiom 8/27/2014
`
`Reference ID: 3642299
`
`
`
`
`
`0 Most-recent draft labeling (ifit is division—proposed labeling, it should be in
`track—changesformat)
`0 Original applicant—proposed labeling
`
`X Included
`
`[Z Included
`
`'2 Incl
`
`1435229221314
`
`RPM: D None 3/27/14
`DMEPA: D None 8/22/14
`DMPP/PLT (DRISK):
`D None 8/26/14
`OPDP: D None 8/26/14
`SEALD: E None
`CSS: E None
`Other: IX None
`
`°2° Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`0 Most-recent draft labeling
`
`02° Proprietary Name
`0 Acceptability/non-acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s)
`
`labeling reviews (indicate dates ofreviews)
`
`00
`
`.0
`
`RPM Filing Review4/Memo of Filing Meeting (indicate date ofeach review)
`All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`March 31, 2014
`
`X Not a (‘90)
`
`
`0O0.00.0
`
`

`

`NDA 205834
`
`Page 4
`
`0
`
`This application is on the AIP
`0
`Ifyes, Center Director’s Exception for Review memo (indicate date)
`
`El Yes
`
`12' No
`
`0
`
`Ifyes. 0C clearance for approval (indicate date ofclearance
`.
`.
`communication)
`
`I:I Not an AP action
`
`0? Pediatrics (approvals only)
`0 Date reviewed by PeRC Auggt 6, 2014
`If PeRC review not necessary, explain:
`
`03° Outgoing communications: letters, emails. and faxes considered important to include in
`the action package by the reviewing oflice/division (e.g.. clinical SPA letters. R'I'F letter.
`etc.
`(do not include revious action letters, as these are located elsewhere in Macka e)
`Internal documents: memoranda, telecons. emails. and other documents considered
`important to include in the action package by the reviewing ofliceldivision (e.g.,
`Regulatory Briefing minutes, Medical Policy Council meeting minutes)
`
`’3'
`
`Included
`
`None
`
`°3° Minutes of Meetings
`
`Ifnot the first review cycle. any end-of-review meeting (indicate date ofmtg)
`
`IE N/A or no mtg
`
`0
`
`0
`
`O
`
`Pre-NDA/BLA meeting (indicate date ofmtg)
`
`EOP2 meeting (indicate date ofmtg)
`
`0 Mid—cycle Communication (indicate date ofmtg)
`
`0
`
`Late-cycle Meeting (indicate date ofmtg)
`
`O Other milestone meetings (e.g., EOP2a. CMC pilots) (indicate dates ofmtgs)
`
`02° Advisory Committee Meeting(s)
`
`0 Date(s) of Meeting(s)
`
`X] No mtg
`
`IX] No mtg
`
`l:] N/A May 21. 2014
`
`E] N/A August 7, 2014
`
`X] No AC meeting
`
`
`
`
`
`°2° Oflice Director Decisional Memo (indicate datefor each review)
`
`I: None October 10, 2014
`
`Division Director Summary Review (indicate datefor each review)
`
`I:] None September 23. 2014
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`I: None August 8, 2014
`
`PMRIPMC Development Templates (indicate total number)
`
`0? Clinical Reviews
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefor each review)
`
`Clinical review(s) (indicate datefor each review)
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`... Fmancral Disclosure revrews(s) glimation/date 1faddressed in another revrew
`Ifno financial disclosure information was required. check here El and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`
`
`IX No separate review
`Review: July 10. 2014
`Filing Checklist: March 11. 2014
`
`[Z None
`
`Clinical Review, Page 199
`
`°2° Clinical reviews fi'om immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`I:] None DTOP May 23. 2014
`DHOP May 19, 2014
`
`°3° Controlled Substance Stafl review(s) and Scheduling Recommendation (indicate date of
`each review)
`
`X N/A
`
`
`
`Version: 8/27/2014
`
`Reference ID: 3642299
`
`

`

`NDA 205834
`
`Page 5
`
`°2° 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)
`
`N/A
`
`D None
`
`O0
`
`.0
`
`OSI Clinical Inspection Review Summary(ies) (include copies ofOSI letters to
`im'estigators)
`
`El None requested June 23, 2014
`
`O0
`
`.0 Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`g No separate review
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`02° 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)
`
`EINoneRewewJuly102014
`Filing Checklist March 11, 2014
`
`I2 No separate review
`
`
`
`D None Review July 10, 2014
`Filing Checklist March 12, 2014
`
`
`
`
`
`
`02° Clinical Pharmacology Division Director Review(s) (indicate datefor each revieuy
`
`I3 No separate review
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`|:I None Review July 10, 2014
`Filin Checklist March 11, 2014
`
`
`.0 OSI Clinical Pharmacology Inspection Review Summary (include copies of OSI letters)
`
`I3 None requested
`
`.0 Pharmacology/1'oxicology Discipline Reviews
`
`00
`
`00
`
`
`
`0 ADP/T Review(s) (indicate datefor each review)
`
`[:1 No separate review July
`152014
`
`0
`
`0
`
`Supervisory Review(s) (indicate datefor each review)
`
`[X No separate review
`
`Pharm/tox review(s), including referenced IND reviews (indicate datefor each
`review)
`
`l:]NoneRev1ewJuly102014
`July 7, 2014
`Filing Checklist March 11, 2014
`
`IE None
`
`IX] No carc
`
`02° Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`for each revieu)
`.0 Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`O0
`
`E] None May 28, 2014
`Included in P/I review. page
`
`g None requested
`
`00
`
`00
`
`.0 ECAC/CAC report/memo of meeting
`
`.0 OSI Nonclinical Inspection Review Summary (include copies ofOSI letters)
`
`Reference ID: 3642299
`
`Versiom 8/27/2014
`
`

`

`NDA 205834
`
`Page 6
`
`°3° Product Quality Discipline Reviews
`
`0 ONDQA/OBP Division Director Review(s) (indicate datefor each review)
`
`IX No separate review
`
`0
`
`0
`
`Branch Chief/ream Leader Review(s) (indicate datefor each review)
`
`X No separate review
`
`Product quality review(s) including ONDQA biopharmaceutics reviews (indicate D None
`datefor each review)
`
`July 11, 2014
`July 10. 2014
`
`03° Microbiology Reviews
`VA NDAs: Microbiology reviews (sterility & pyrogenicity) (OPS/NDMS) (indicate
`date ofeach review)
`I:I BLAs: Sterility assurance, microbiology, facilities reviews
`(OMPQ/MAPCB/BMT) (indicate date ofeach review)
`
`°3° Reviews by other discipfines/div'isionleenters requested by CMC/quality reviewer
`.
`.
`.
`(indicate date ofeach review)
`
`°3° Environmental Assessment (check one) (original and supplemental applications)
`
`El Not needed
`March 31. 2014
`
`N/A
`
`IX None
`
`IX Categorical Exclusion (indicate review date)(all original applications and
`all efi‘icacv supplements that could increase thepatientpopulation)
`
`not
`
`2
`
`lty Revnew pg. 136
`
`El Review & FONSI (indicate date of review)
`
`El Review & Environmental Impact Statement (indicate date ofeach review)
`
`N/A
`
`NlA
`
`
`
`02° Facilities Review/Inspection
`
`g 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
`facility or a change that afi'ects the manufacturing sitesj)
`I:| BLAs: TB-EER (date ofmost recent TB-EER must be within 30 days ofaction
`date) (original and supplemental BLAs)
`
`°2° NDAs: Methods Validation (check box only, do not include documents)
`
`
`
`Date completed: Sept. 3. 2014
`IE Acceptable
`I:] Withhold recommendation
`
`
`atrigtblg:
`D Withhold recommendation
`
`IE Completed
`R
`est
`El
`equ
`ed
`I: Not yet requested
`I:] Not needed (per review)
`
`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.
`
`Versiom 8/27/2014
`
`Reference ID: 3642299
`
`

`

`NDA 205834
`
`Page 7
`
`
`.
`-
`-
`.
`.
`.
`_
`.
`~.° For all 505(b)(2) applications.
`. Check Orange Book for newly listed patents and/or exclusivity (including
`agggigexclusmty (Nonjj
`
`I No changes
`
`pediatric exclusivity)
`
`-
`
`Finalize 505(b)(2) assessment
`
`°3° Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
`
`'2'
`
`If an FDA communication will issue, notify Press Office of approval action after
`confirming that applicant received comtesy copy of approval letter
`~30 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
`identified as the ‘ referred” name
`
`0:0 Ensure Pediatric Record is accurate
`
`02° Send approval email within one business day to CDER-APPROVALS
`
`
`D Done
`
`
`
`IE Done
`
`IX Done
`
`IE Done
`
`E Done
`
`IX Done
`
`
`
`
`
`Reference ID: 3642299
`
`Versiom 8/27/2014
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`10/10/2014
`
`Reference ID: 3642299
`
`

`

`From:
`To:
`Cc:
`Subject:
`Date:
`
`Michele Anderson
`Onaga, Linda
`Regulatory Archives; Prachi Shah
`RE: IND 115268 and NDA 205834
`Wednesday, September 17, 2014 4:36:10 PM
`
`Hi Linda,
`
`We agree to make this change and will submit a revised label ASAP.
`
`Thank you,
`Michele
`
`From: Onaga, Linda [mailto:Linda.Onaga@fda.hhs.gov]
`Sent: Wednesday, September 17, 2014 1:24 PM
`To: Michele Anderson
`Cc: Regulatory Archives; Prachi Shah
`Subject: RE: IND 115268 and NDA 205834
`
`Michele,
`
`We have an additional edit the Harvoni label:
`
`Please modify the following sentence in Section 14 Microbiology
`
`FROM: Sustained virologic response (SVR) was the primary endpoint
`
` was defined as HCV RNA less than LLOQ at 12 weeks after
`the cessation of treatment.
`
`TO: Sustained virologic response (SVR) was the primary endpoint and was defined
`as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment.
`
`
`Please let me know if you agree to this change if so please submit a revised label
`
`Linda.
`
`From: Michele Anderson [mailto:Michele.Anderson@gilead.com]
`Sent: Wednesday, September 17, 2014 3:16 PM
`To: Onaga, Linda
`Cc: Regulatory Archives; Prachi Shah
`Subject: RE: IND 115268 and NDA 205834
`
`Dear Linda,
`
`Attached please find Gilead’s response to the 16 September labeling comments for NDA 205834.
`We have agreed with all comments provided. This information will be submitted through the
`gateway shortly.
`
`Reference ID: 3633827
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`If you could let me know whether additional labeling comments should be expected I would
`appreciate it.
`
`Thank you,
`Michele
`
`From: Onaga, Linda [mailto:Linda.Onaga@fda.hhs.gov]
`Sent: Tuesday, September 16, 2014 1:58 PM
`To: Michele Anderson
`Subject: IND 115268 and NDA 205834
`
`Good Afternoon Michele,
`
`
`Please find attached comments for IND 115268 SD 190 and NDA 205834 labeling comments from
`the Division and SEALD team.
`
`We request a response to the labeling comments by Thursday.
`
`Thanks
`
`Linda
`
`Linda C. Onaga, MPH
`Senior Regulatory Project Manager
`Division of Antiviral Products (DAVP)
`FDA/CDER/OND/OAP
`White Oak Complex, Bldg 22, Rm 6321
`10903 New Hampshire Ave.
`Silver Spring, MD 20993
`Ph: 301.796.0759
`Fax: 301.796.9883
`Email: linda.onaga@fda.hhs.gov
`
`
`Reference ID: 3633827
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`09/24/2014
`
`Reference ID: 3633827
`
`

`

`From:
`To:
`Cc:
`Subject:
`Date:
`
`Michele Anderson
`Onaga, Linda
`Jennifer Huber; Prachi Shah
`Re: NDA 205834 PMC
`Wednesday, September 24, 2014 3:20:46 PM
`
`Hi Linda
`Thank you for your email. We will respond today.
`Thanks,
`Michele
`
`On Sep 24, 2014, at 8:06 PM, "Onaga, Linda"
`<Linda.Onaga@fda.hhs.gov<mailto:Linda.Onaga@fda.hhs.gov>> wrote:
`
`We request a response before close of business today.
`
`Thanks
`
`Linda
`
`From: Onaga, Linda
`Sent: Wednesday, September 24, 2014 3:03 PM
`To: michele.anderson@gilead.com<mailto:michele.anderson@gilead.com>; Jennifer Huber
`(Jennifer.Huber@gilead.com<mailto:Jennifer.Huber@gilead.com>)
`Cc: Prachi Shah (Prachi.Shah@gilead.com<mailto:Prachi.Shah@gilead.com>)
`Subject: NDA 205834 PMC
`Importance: High
`
`Good Afternoon Michele,
`
`Please find below an additional PMC that we are adding for the LDV/SOF NDA. Please provide timelines
`for the listed PMC.
`
`PMC:
`Submit an interim study report from the ongoing study GS-US-248-0122, entitled, “A Long Term Follow-
`up Registry for Subjects Who Achieve a Sustained Virologic Response to Treatment in Gilead-Sponsored
`Trials in Subjects with Chronic Hepatitis C Infection”, with the three year follow-up data from: GS-US-
`337-0102 (ION-1), GS-US-337-0109 (ION-2), GS-US-337-0108 (ION-3).
`
`PMR/PMC Schedule Milestones:
`
`Final Protocol Submission:
`
`Study/Trial Completion:
`
`Final Report Submission:
`
`Reference ID: 3633808
`
`

`

`Please submit your response by 9/25/14.
`
`Thanks
`
`Linda
`
`Linda C. Onaga, MPH
`Senior Regulatory Project Manager
`Division of Antiviral Products (DAVP)
`FDA/CDER/OND/OAP
`White Oak Complex, Bldg 22, Rm 6321
`10903 New Hampshire Ave.
`Silver Spring, MD 20993
`Ph: 301.796.0759
`Fax: 301.796.9883
`Email: linda.onaga@fda.hhs.gov<mailto:linda.onaga@fda.hhs.gov>
`
`Reference ID: 3633808
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`09/24/2014
`
`R