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` NDA 214324
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`NDA APPROVAL
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`United Therapeutics Corp.
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`Attention: Sarah Gemberling, PhD, RAC
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`Manager, Regulatory Affairs
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`55 TW Alexander Drive, PO Box 14186
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`Research Triangle Park, NC 27709
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`Dear Dr. Gemberling:
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`Please refer to your new drug application (NDA) dated April 16, 2021, received
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`April 16, 2021, and your amendments, submitted under section 505(b) of the Federal
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`Food, Drug, and Cosmetic Act (FDCA) for Tyvaso DPI (treprostinil) inhalation powder.
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`We acknowledge receipt of your amendment dated December 23, 2021, which
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`constituted a complete response to our October 15, 2021, action letter.
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`We acknowledge receipt of your major amendment dated February 18, 2022, which
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`extended the goal date by three months.
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`This NDA provides for the use of Tyvaso DPI (treprostinil) inhalation powder for the
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`treatment of pulmonary arterial hypertension (PAH; WHO Group I) and pulmonary
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`hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3), to
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`improve exercise ability.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved, effective
`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
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information, and Instructions for Use) as well as annual reportable changes
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`not included in the enclosed labeling. Information on submitting SPL files using eLIST
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 4987774
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` NDA 214324
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` Page 2
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` may be found in the guidance for industry SPL Standard for Content of Labeling
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` Technical Qs and As.2
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND CONTAINER LABELING
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`Submit final printed carton and container labeling that are identical to the enclosed
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`carton and container labeling , as soon as they are available, but no more than 30 days
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`after they are printed. Please submit these labeling electronically according to the
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`guidance for industry Providing Regulatory Submissions in Electronic Format — Certain
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`Human Pharmaceutical Product Applications and Related Submissions Using the eCTD
`Specifications. For administrative purposes, designate this submission “Final Printed
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`Carton and Container Labeling for approved NDA 214324.” Approval of this
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`submission by FDA is not required before the labeling is used.
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`DATING PERIOD
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`Based on the stability data submitted to date, the expiry dating period for Tyvaso DPI
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`(treprostinil) inhalation powder shall be 18 months from the date of manufacture when
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`stored at 2°C to 8°C (36°F to 46°F).
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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 has an orphan drug designation for the treatment of PAH,
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`you are exempt from this requirement for the PAH indication only.
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`We are waiving the pediatric study requirement for the treatment of PH-ILD because
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`necessary studies are impossible or highly impracticable considering the number of
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`pediatric patients with PH-ILD is extremely rare.
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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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` 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: 4987774
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` NDA 214324
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` Page 3
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` Electronic Format—Promotional Labeling and Advertising Materials for Human
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` Prescription Drugs.3
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials,
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`and the Prescribing Information, at the time of initial dissemination or publication,
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`accompanied by a Form FDA 2253. Form FDA 2253 is available at FDA.gov.4
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`Information and Instructions for completing the form can be found at FDA.gov.5
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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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`Your product is a Part 3 combination product (21 CFR 3.2(e)); therefore, you must also
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`comply with postmarketing safety reporting requirements for an approved combination
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`product (21 CFR 4, Subpart B). Additional information on combination product
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`postmarketing safety reporting is available at FDA.gov.6
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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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`Norman Stockbridge, MD, PhD
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`Director
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`Division of Cardiology and Nephrology
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`Office of Cardiology, Hematology, Endocrinology, and
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`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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`Instructions for Use
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`• Carton and Container Labeling
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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
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` 6 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety
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`reporting-combination-products
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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: 4987774
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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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`NORMAN L STOCKBRIDGE
`05/23/2022 08:55:05 AM
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`Reference ID: 4987774
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`(b)
`(4)
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