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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 22387/S-015
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`United Therapeutics Corporation
`Attention: Rita Lee, PhD, RAC
`Senior Scientist, Regulatory Affairs
`55 TW Alexander Drive, PO Box 14186
`Research Triangle Park, NC 27709
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`Dear Dr. Lee:
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`Please refer to your Supplemental New Drug Application (sNDA) dated December 19, 2016,
`received December 19, 2016, and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Tyvaso® (Treprostinil) Inhalation Solution,
`0.6mg.
`
`This Prior Approval supplemental new drug application proposes the following changes: a third
`generation nebulizer for the Tyvaso Inhalation System, the TD-300/A Tyvaso Inhalation Device,
`as well as changes to the Prescribing Information, Patient Leaflet, Instructions for Use, and
`carton and container labels to account for the new nebulizer.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`We have the following comment for future consideration:
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`Two participants in the HF study for the 3rd generation Tyvaso Inhalation System
`experienced difficulty with screwing the dome assembly on to the device. If
`there is an opportunity to optimize the Tyvaso Inhalation System in the future,
`we recommend that you modify the dome assembly for easier connection.
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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
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described
`athttp://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
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`Reference ID: 4169842
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`

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`NDA 22387/S-015
`Page 2
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`Content of labeling must be identical to the enclosed labeling (text for the Prescribing
`Information, text for the Patient Leaflet, Instructions for Use), with the addition of any labeling
`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual 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 industry titled
`“SPL Standard for Content of Labeling Technical Qs and As” at
`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
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft 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 IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and immediate container labels that are identical to the enclosed
`carton and immediate container labels as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labels electronically according to the guidance for
`industry titled Providing Regulatory Submissions in Electronic Format — Certain Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(May 2015, Revision 3). For administrative purposes, designate this submission “Final Printed
`Carton and Container Labels for approved NDA ######/S-###.” Approval of this
`submission by FDA is not required before the 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 new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are exempt
`from this requirement.
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`Reference ID: 4169842
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`

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`NDA 22387/S-015
`Page 3
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and 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 annotated references, and
`(3) the package insert(s) to:
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`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
`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
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more 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
`(21 CFR 314.80 and 314.81).
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`Reference ID: 4169842
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`

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`NDA 22387/S-015
`Page 4
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`If you have any questions, call Wayne Amchin, RAC, Regulatory Project Manager, at (301) 796-
`0421.
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, M.D., Ph.D.
`Director
`Division of Cardiovascular and Renal Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
`Carton and Container Labeling
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`Reference ID: 4169842
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`

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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/
`----------------------------------------------------
`
`WAYNE S AMCHIN
`10/19/2017
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`NORMAN L STOCKBRIDGE
`10/19/2017
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`Reference ID: 4169842
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