Issued January 3, 2025
Issued
January 3, 2025
Application
NDA 505b1 • 218879
Review center
CDER
Stage
Final Decision
Letter type
Complete Response Letter
This FDA letter for NDA 218879 outlines deficiencies and requirements for the applicant to address in a resubmission. It details specific instructions for revising prescribing information, updating carton and container labeling, and comprehensively presenting new safety data from clinical studies and worldwide experience. The letter also sets a one-year deadline for resubmission or other actions and clarifies the process for resubmission and potential meetings.
The FDA issued a Complete Response Letter for NDA 218879, citing significant deficiencies primarily related to the clinical safety data analysis and presentation, as well as incomplete labeling information. Key issues include inadequate adverse event reporting, missing case report forms and narrative summaries for serious events, outdated exposure information, and a lack of comprehensive worldwide safety experience. Additionally, specific comments on carton and container labeling, and general prescribing information comments, need to be addressed.
Draft carton and container labeling comments need to be addressed in any subsequent resubmission. Specific comments were redacted.
Recommended response: Revise carton and container labeling per agency comments and ensure all specific feedback is incorporated.
New safety data from clinical trials for the proposed indication must be presented using the same format as the original submission. Tabulations of new safety data combined with original application data are required, along with tables comparing frequencies of adverse events. Separate tables for adverse events occurring in clinical trials for indications other than the proposed indication must also be provided.
Recommended response: Re-analyze and re-present all safety data, ensuring comprehensive tabulations, comparisons, and separate tables for different indications as requested.
A retabulation of the reasons for premature trial discontinuation is required, incorporating dropouts from newly completed trials. Any new trends or patterns identified must be described.
Recommended response: Update and re-analyze data on premature trial discontinuations, providing a detailed description of any new trends.
Case report forms and narrative summaries must be provided for each subject who died during a clinical trial or who did not complete a trial due to an adverse event. Additionally, narrative summaries for all serious adverse events are required.
Recommended response: Compile and submit all requested case report forms and narrative summaries for deaths and serious adverse events.
Information suggesting a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data must be described.
Recommended response: Conduct a thorough comparative analysis of common adverse events between new and original data, highlighting any significant changes.
Updated exposure information for the clinical studies/trials (e.g., number of subjects, person time) must be provided.
Recommended response: Update and submit comprehensive clinical exposure data for all relevant studies.
A summary of worldwide experience on the safety of this drug is required, including an updated estimate of use for the drug marketed in other countries.
Recommended response: Compile and submit a comprehensive worldwide safety summary, including usage estimates from other markets.
English translations of current approved foreign labeling not previously submitted must be provided.
Recommended response: Obtain and submit English translations for all current approved foreign labeling that has not yet been provided.
The agency reserves comment on the proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review labeling review resources, including regulations and related guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.
Recommended response: Proactively review and revise prescribing information using FDA resources and the SRPI checklist to ensure compliance with format and content requirements.
Cited: 21 CFR 314.50(l)(1)(i)
The primary themes of the Complete Response Letter are significant deficiencies in the clinical safety data, including analysis, presentation, and completeness of reporting, alongside various labeling inadequacies.
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.