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`Food and Drug Administration
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` Silver Spring MD 20993
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` NDA APPROVAL
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203496
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`Reference ID: 3426495
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`United Therapeutics Corporation
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`Attention: Dean Bunce, RAC
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`Executive Vice President,
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`Regulatory Affairs and Compliance
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`55T. W. Alexander Drive
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`P.O. Box 14186
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`Research Triangle Park, NC 27709
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`Dear Mr. Bunce:
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`Please refer to your New Drug Application (NDA) dated December 23, 2011, received
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`December 27, 2011, resubmitted January 31 and August 16, 2013, under section 505(b)(1) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA), for Orenitram (Treprostinil) Extended Release
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`Tablets, 0.125 mg, 0.25 mg, 1mg, and 2.5 mg.
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`We acknowledge receipt of your amendments dated August 16, 20, September 13, October 8, 29,
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`November 27, and December 18, 2013.
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`The August 16, 2013, submission constituted a complete response to our March 22, 2013, action
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`letter.
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`This new drug application provides for the use of Orenitram (Treprostrinil) Extended Release
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`Tablets, 0.125 mg, 0.25 mg, 1mg, and 2.5 mg for treatment of pulmonary arterial hypertension
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`(PAH) (WHO Group 1) to improve exercise capacity.
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`We have completed our review of this application, as amended. It is approved, effective on the
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`date of this letter, for use as recommended in the enclosed agreed-upon labeling 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, text for the
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` patient package insert). Information on submitting SPL files using eLIST may be found in the
` guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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`CM072392.pdf.
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` NDA 203496
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` Page 2
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` The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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` We acknowledge your October 29, 2013, submission containing final printed carton and
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` container labels.
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`Please submit final printed carton and immediate container labels that are identical to the carton
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`and immediate container labels submitted on October 29, 2013, as soon as they are available, but
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`no more than 30 days after they are printed. Please submit these labels electronically according
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`to the guidance for industry Providing Regulatory Submissions in Electronic Format – Human
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`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
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`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
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`submission “Final Printed Carton and Container Labels for approved NDA 203496.”
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`Approval of this submission by FDA is not required before the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
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`product misbranded and an unapproved new drug.
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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 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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`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, in triplicate, a cover letter requesting advisory comments, the
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`proposed materials in draft or mock-up form with annotated references, and the package insert
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`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
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
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`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
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`Reference ID: 3426495
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` NDA 203496
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` Page 3
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` 2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
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` information about submission of promotional materials to the Office of Prescription Drug
` 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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`If you have any questions, please call Wayne Amchin, Regulatory Project Manager, at (301)
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`796-0421.
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`Sincerely,
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` {See appended electronic signature page}
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` Norman Stockbridge, MD, PhD
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` Director
` Division of Cardiovascular and Renal
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` Products
` Office of Drug Evaluation I
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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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`Carton and Container Labeling
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`Reference ID: 3426495
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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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`NORMAN L STOCKBRIDGE
`12/20/2013
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`Reference ID: 3426495
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