Issued January 1, 2022
Issued
January 1, 2022
Application
Other • 214324
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response Letter from the FDA to United Therapeutics Corp. regarding their New Drug Application (NDA) 214324 for treprostinil inhalation powder. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, prescribing information, proprietary name resubmission, and the need for a comprehensive safety update.
The New Drug Application for treprostinil inhalation powder received a Complete Response due to a critical Official Action Indicated (OAI) classification for the manufacturing facility, requiring satisfactory resolution of CGMP deficiencies. Additionally, comprehensive safety data updates are required, along with revised prescribing information and carton/container labeling. The proposed proprietary name needs to be resubmitted with the response.
The manufacturing facility for this application has been classified as Official Action Indicated (OAI) for drug CGMP following a recent inspection. Satisfactory resolution of these deficiencies is required before the application can be approved.
Recommended response: Address and resolve all CGMP deficiencies at the manufacturing facility to achieve a satisfactory inspection outcome.
Cited: drug CGMP
A comprehensive safety update is required, including data from all nonclinical and clinical studies/trials. This involves describing significant changes in the safety profile, incorporating new safety data into adverse event sections, retabulating reasons for premature trial discontinuation, providing case report forms and narrative summaries for deaths/serious adverse events, updating exposure information, summarizing worldwide safety experience, and providing English translations of foreign labeling.
Recommended response: Compile and submit a complete safety update package as per 21 CFR 314.50(d)(5)(vi)(b), ensuring all requested data, narratives, and summaries are included and updated.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Further comments on the proposed prescribing information are reserved until the application is otherwise adequate. The sponsor is encouraged to review labeling resources and guidance documents, including the SRPI checklist, to ensure conformity with format items in regulations and guidances. Updated content of labeling must be included in the response.
Recommended response: Revise the prescribing information according to FDA regulations and guidances, utilizing the SRPI checklist, and include the updated content of labeling in the resubmission.
Cited: 21 CFR 314.50(l)(1)(i)
Further comments on the proposed carton and container labeling are reserved until the application is otherwise adequate.
Recommended response: Address primary application deficiencies before resubmitting revised carton and container labeling.
The proposed proprietary name, Tyvaso DPI, was found acceptable pending approval of the application. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name (Tyvaso DPI) along with the response to all other application deficiencies.
A citizen petition (Docket No. FDA-2021-P-0714) regarding the approvability of NDA 214324 for Tyvaso DPI is currently under review by the Agency. FDA has not made a final decision on the issues raised by this petition, and the current deficiency comments are independent of this petition.
Recommended response: Monitor the status and outcome of the citizen petition, as it may influence future regulatory decisions, although current deficiencies must be addressed independently.
The primary themes are critical manufacturing quality control issues (OAI), the need for a thorough and updated safety data package, and general labeling compliance, all of which are essential for approval. An ongoing citizen petition also presents an external factor.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
Document viewer
Read the FDA letter and send context to the co-pilot at any time.