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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205834/S-1
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Gilead Sciences, Inc.
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` Attention: Prachi Shah, MBS, RAC
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` Associate Manager, Regulatory Affairs
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` 333 Lakeside Drive
` Foster City, CA 94404
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`Dear Ms. Shah:
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`Please refer to your Supplemental New Drug Application (sNDA) dated March 18, 2015,
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`received March 19, 2015, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Harvoni® (ledipasvir/sofosbuvir), fixed-dose combination tablet, 90
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`mg/400 mg.
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`We acknowledge receipt of your amendment dated March 19, 2015.
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`This Changes Being Effected supplemental new drug application proposed the following change:
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`• To update the WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and
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`DRUG INTERACTIONS sections of the label and the patient package insert with
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`information on post-marketing cases of serious symptomatic bradycardia when
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`amiodarone is co-administered with Harvoni® (ledipasvir/sofosbuvir).
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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` of labeling must be identical to the enclosed labeling (text for the package insert and text for the
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` patient package insert) with the addition of any labeling changes in pending “Changes Being
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` Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
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`labeling.
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`Reference ID: 3719465
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` NDA 205834/S1
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` Page 2
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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
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.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 includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`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
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` annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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` up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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` should provide appropriate annotations, including supplement number(s) and annual report
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` date(s).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`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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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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`Reference ID: 3719465
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, MD
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`Director
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`Antiviral Products
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`Office of Antimicrobial Products
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`Center for Drug Evaluation and Research
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` NDA 205834/S1
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` Page 3
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` REPORTING REQUIREMENTS
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` We remind you that you must comply with reporting requirements for an approved NDA
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` (21 CFR 314.80 and 314.81).
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`If you have any questions, call Linda C. Onaga, MPH, Senior Regulatory Project Manager, at
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`(301) 796-0759 or the Division mainline at (301) 796-1500.
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3719465
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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
`03/20/2015
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`Reference ID: 3719465
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