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` NDA 205834/S-031
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` NDA 212477/S-001
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`SUPPLEMENT APPROVAL
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` Gilead Sciences, Inc.
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` Attention: Hilary White
` Associate II, Regulatory Affairs
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` 333 Lakeside Drive
` Foster City, CA 94404
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`Dear Ms. White:
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`Please refer to your supplemental new drug applications (sNDAs), dated and received
`on March 19, 2019 for HARVONI® (ledipasvir and sofosbuvir) tablets, 90 mg/400 mg
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`and 45 mg/200 mg and September 5, 2019, for HARVONI® (ledipasvir and sofosbuvir)
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`oral pellets, 33.75 mg/150 mg and 45 mg/200 mg, and your amendments, submitted
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`under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA).
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`These Prior Approval supplemental new drug applications provide for an update to the
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`DRUG INTERACTIONS section, 7.2 subsection with information regarding the risk of
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`dysglycemia in patients with diabetes who received direct-acting antiviral drugs for the
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`treatment of chronic hepatitis C virus infection.
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`APPROVAL & LABELING
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`We have completed our review of these applications, as amended. They are approved,
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`effective on the date of this letter, for use as recommended in the enclosed agreed-
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`upon labeling.
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`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information and Patient Package Insert), with the addition of any labeling
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 4494162
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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
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`Office of Antimicrobial Products
`
`Center for Drug Evaluation and Research
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` NDAs 205834/S-031 & 212477/S-001
` Page 2
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` changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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` 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
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`industry SPL Standard for Content of Labeling Technical Qs and As.2
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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
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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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 Kyong Hyon, Safety Regulatory Project Manager, at 301
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`796-0734.
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`ENCLOSURE(S):
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`• Content of Labeling
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`o Prescribing Information
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`o Patient Package Insert
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4494162
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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`POONAM MISHRA
`09/19/2019 11:55:28 AM
`on behalf of Debra Birnkrant
`
`Reference ID: 4494162
`
`(
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`