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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 205834/S-024
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Gilead Sciences, Inc.
`Attention: Linda Lintao, RAC
`Manager, Regulatory Affairs
`333 Lakeside Drive
`Foster City, CA 94404
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`Dear Ms. Lintao:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received September
`14, 2017, and your amendment, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for HARVONI® (ledipasvir and sofosbuvir), fixed-dose combination
`tablet, 90 mg/400 mg.
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`This Prior Approval supplemental new drug application provides for the followings revisions:
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`• Update the DRUG INTERACTIONS section with information pertaining to fluctuations
`in International Normalized Ratio (INR) values in patients receiving warfarin
`concomitantly with HARVONI.
`• Update the DRUG INTERACTIONS section regarding the potential drug interaction
`between HARVONI and atorvastatin.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of prescribing information.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described
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`Reference ID: 4179390
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`NDA 205834/S-024
`Page 2
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`at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
`Content of labeling must be identical to the enclosed labeling (text for the package insert, text for
`the patient package insert), with the addition of any labeling changes in pending “Changes Being
`Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
`labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As”
`at http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/
`UCM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available
`at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
`s/UCM443702.pdf ).
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`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available
`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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`Reference ID: 4179390
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`NDA 205834/S-024
`Page 3
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`Information and Instructions for completing the form can be found
`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf.
`For more information about submission of promotional materials to the Office of Prescription
`Drug Promotion (OPDP),
`see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Kyong Hyon, Safety Regulatory Project Manager, at (301) 796-
`0734.
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, MD
`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`
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`Reference ID: 4179390
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`POONAM MISHRA
`11/09/2017
`on behalf of Debra Birnkrant, MD
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`Reference ID: 4179390
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