( .I# I U.S. FOOD & DRUG
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`,.,. .........
`•-..:::::i~
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`ADMINISTRATION
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`NDA 203284/S-012
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`SUPPLEMENT APPROVAL
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` Horizon Therapeutics, LLC
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` Attention: Adam Junia
` Director Regulatory Affairs
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` 1 Horizon Way
` Deerfield, IL 60015
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`Dear Mr. Junia:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`March 3, 2021, and your amendments, submitted under section 505(b) of the Federal
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`Food, Drug, and Cosmetic Act (FDCA) for Ravicti (glycerol phenylbutyrate).
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`This Prior Approval sNDA provides for updates to the Ravicti labeling to add information
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`regarding the in-use stability of the product as well as remove references to a
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`pregnancy registry.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved, effective
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`on the date of this letter, for use as recommended in the enclosed agreed-upon
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`labeling.
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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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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`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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`Reference ID: 4852147
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` NDA 203284/S-012
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` Page 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
`supplement number(s) and annual report date(s).
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` CARTON AND CONTAINER LABELING
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`Submit final printed carton and container labeling that are identical to the carton and
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`container labeling submitted on July 22, 2021, as soon as they are available, but no
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`more than 30 days after they are printed. Please submit these labeling electronically
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`according to the guidance for industry Providing Regulatory Submissions in Electronic
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`Format — Certain Human Pharmaceutical Product Applications and Related
`Submissions Using the eCTD Specifications. For administrative purposes, designate
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`this submission “Final Printed Carton and Container Labeling for approved
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`NDA 203284/S-012.” Approval of this submission by FDA is not required before the
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`labeling is used.
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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. Because this drug product for this indication has an orphan drug
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`designation, you are exempt from this requirement.
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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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`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: 4852147
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`NDA 203284/S-012
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`Page 3
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`If you have any questions, call Diego A. Diaz, Regulatory Project Manager, at (301)
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`796-7182.
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`Sincerely,
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`{See appended electronic signature page}
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`Patroula Smpokou, M.D.
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`Deputy Director
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`Division of Rare Diseases and Medical
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`Genetics (DRDMG)
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`Office of Rare Diseases, Pediatrics, Urologic
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`and Reproductive Medicine (ORPURM)
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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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`• Carton and Container Labeling
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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: 4852147
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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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`PATROULA I SMPOKOU
`09/03/2021 03:54:03 PM
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`Reference ID: 4852147
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