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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203284/004
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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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` Horizon Therapeutics, LLC
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`Attention: Jeffrey W. Sherman, M.D.
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` Chief Medical Officer and Executive Vice President
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` 150 S. Saunders Road
` Lake Forrest, IL 60045
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`Dear Dr. Sherman:
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`Please refer to your Supplemental New Drug Application (sNDA) dated, November 19, 2015,
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`received November 19, 2015, and your amendments, submitted pursuant to section 505(b)(2) of
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`the Federal Food, Drug, and Cosmetic Act (FDCA) for RAVICTI (glycerol phenylbutyrate) oral
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`liquid.
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`This Prior Approval supplemental new drug application proposes to include:
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`• Additional information to Section 7 Drug Interactions and Section 12 Clinical
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`Pharmacology on the potential for RAVICTI to interact with CYP3A4 and CYP2C9
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`substrates
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`• Modification of Section 2 of the Prescribing Information, Dosage and Administration, to
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`include a dosing conversion for patients switching from sodium phenylbutyrate powder
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`to RAVICTI.
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`• Additional adverse reactions identified during post-approval use added to Section 6.2
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`Postmarketing Experience
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`• Conversion of Section 8.1 Pregnancy and 8.2 Lactation to follow the Pregnancy and
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`Lactation Labeling Rule (PLLR) format.
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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 with the minor editorial revisions indicated in the enclosed labeling.
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`We note that your September 8, 2016, submission includes final printed labeling (FPL) for your
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`package insert and medication guide. We have not reviewed this FPL. You are responsible for
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`assuring that the wording in this printed labeling is identical to that of the approved content of
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`labeling in the structured product labeling (SPL) format.
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`Reference ID: 3983369
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` NDA 203284/004
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` Page 2
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` REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are exempt
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`from this requirement.
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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, 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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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“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 include 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
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`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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`Reference ID: 3983369
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` NDA 203284/004
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` Page 3
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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
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`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
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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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`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
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`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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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`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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`Reference ID: 3983369
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` NDA 203284/004
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` Page 4
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` If you have any questions, call Kelly Richards, Senior Regulatory Health Project Manager, at
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` (240) 402-4276.
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`Sincerely,
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`{See appended electronic signature page}
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`Dragos Roman, M.D.
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`Associate Director
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`Division of Gastroenterology and Inborn Errors
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`Products
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`Office of Drug Evaluation III
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3983369
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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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`DRAGOS G ROMAN
`09/08/2016
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`Reference ID: 3983369
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