`NDA 203284/S-011
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`SUPPLEMENT APPROVAL
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` Horizon Therapeutics
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` Nicole Potthast, RN, BSN, MBA
` Director, Regulatory Affairs
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` 150 S. Saunders Road
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` Lake Forest, IL 60045
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`Dear Ms. Potthast:
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`Please refer to your supplemental new drug application (sNDA), received March 28,
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`2019, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic
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`Act (FDCA) for Ravicti (glycerol phenylbutyrate) oral liquid.
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`This supplemental new drug application provides for the following revisions to the
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`Prescribing Information:
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`- Updated efficacy and safety data in pediatric patients age 2 months to less than 2
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`years
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`- Revised text regarding the through QT study in Section 12.2 Pharmacodynamics.
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`APPROVAL & LABELING
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`We completed our review of the application. It is approved, effective on the date of this
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`letter, for use as recommended in the enclosed agreed-upon labeling with minor
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`editorial revisions listed below and reflected in the enclosed labeling.
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`- Update the revision date at the end of Highlights of the Prescribing Information to
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`the approval date. Also, update the revision date at the end of the Medication
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`Guide.
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`Reference ID: 4501848
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` NDA 203284/S-011
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` Page 2
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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
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` FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information and Medication Guide), with the addition of any labeling
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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
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`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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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
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`new active ingredients (which includes new salts and new fixed combinations), new
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`indications, new dosage forms, new dosing regimens, or new routes of administration
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`are required to contain an assessment of the safety and effectiveness of the product for
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`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are
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`exempt from this requirement.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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` 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: 4501848
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` NDA 203284/S-011
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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
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` 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
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` annotated references, and (3) the Prescribing Information 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
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`format. For more information about submitting promotional materials in eCTD format,
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`see the draft guidance for industry Providing Regulatory Submissions in Electronic and
`Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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`You must submit final promotional materials and Prescribing Information, accompanied
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`by a Form FDA 2253, at the time of initial dissemination or publication
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`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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`Instructions for completing the form can be found at FDA.gov.5 For more information
`about submission of promotional materials to the Office of Prescription Drug Promotion
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`(OPDP), see FDA.gov.6
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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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` 3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
` version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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` 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.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: 4501848
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` NDA 203284/S-011
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` Page 4
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` If you have any questions, contact Nicolas Kong, Regulatory Project Manager at
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` Nicolas.Kong@fda.hhs.gov or 240-402-0269.
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` Sincerely,
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`{See appended electronic signature page}
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`
`Lisa Soule, 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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`ENCLOSURES:
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`• Content of Labeling
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`o Prescribing Information
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`o Medication Guide
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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: 4501848
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`Signature Page 1 of 1
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`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.
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`/s/
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`LISA M SOULE
`10/04/2019 10:18:48 AM
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`Reference ID: 4501848
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`(
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