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` NDA 022387/S-020
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`SUPPLEMENT APPROVAL
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`United Therapeutics Corp.
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`Attention: Nicole Wilkerson
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`Associate Director, Regulatory Affairs
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`55 T.W. Alexander Drive, P.O. Box 14186
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`Research Triangle Park, NC 27709
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`Dear Ms. Wilkerson:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`May 13, 2022, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
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`Act (FDCA) for Tyvaso (treprostinil) inhalation solution.
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`This “Changes Being Effected” sNDA provides for the addition of Bronchospasm to the
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`WARNINGS AND PRECAUTIONS section of the Package Insert.
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`APPROVAL & LABELING
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`We have completed our review of this application. It is approved, effective on the date of
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`this letter, for use as recommended in the enclosed agreed-upon 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), with the addition of any labeling changes in pending “Changes
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`Being Effected” (CBE) supplements, as well as annual reportable changes not included
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`in the enclosed labeling. If the content of labeling in SPL format initially submitted with
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`this CBE-0 labeling supplement is identical to the attached approved labeling, an
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`additional submission of content of labeling in SPL format is not required.
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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
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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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`Reference ID: 4987170
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` NDA 022387/S-020
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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
`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
`Word version. The marked-up copy should provide appropriate annotations, including
`supplement number(s) and annual report date(s).
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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. For information about submitting promotional materials, see the
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`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
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`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
` [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
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`All promotional materials that include representations about your drug product must be
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`promptly revised to be consistent with the labeling changes approved in this
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`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
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`in your promotional materials should include prominent disclosure of the important new
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`safety information that appears in the revised labeling. Within 7 days of receipt of this
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`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4).
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`PATENT LISTING REQUIREMENTS
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`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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`submitted in a supplement require you to submit patent information for listing in the
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`Orange Book upon approval of the supplement. You must submit the patent information
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`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
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`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
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`supplement for the patent information to be timely filed (see 21 CFR
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`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
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`require the submission of a request to remove patent information from the Orange Book
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` 3 For the most recent version of a guidance, check the FDA guidance web page at
` https://www.fda.gov/media/128163/download.
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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
`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4987170
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` NDA 022387/S-020
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` Page 3
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` are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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` 314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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 Brian Cooney, Regulatory Project Manager, at
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`(301) 796-0886.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Ross Southworth, PharmD
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`Deputy Director for Safety
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`Division of Cardiology and Nephrology
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`Office of Cardiology, Hematology,
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`Endocrinology, and Nephrology
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`Office of New Drugs
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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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`o Prescribing Information
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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: 4987170
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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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`MARY R SOUTHWORTH
`05/20/2022 01:14:37 PM
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`Reference ID: 4987170
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`(
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