Issued July 11, 2024
Issued
July 11, 2024
Application
NDA 505b1 • 215029
Review center
CDER
Stage
Final Decision
Letter type
Complete Response Letter
This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 215029. It outlines deficiencies in the application, reserves comment on proposed labeling, addresses the proprietary name, and provides detailed instructions for a safety update and the resubmission process. The letter also specifies the timeframe for resubmission and options for meetings.
The application received a Complete Response due to significant deficiencies primarily related to the safety update, requiring comprehensive re-analysis and presentation of clinical safety data, including case report forms for serious adverse events and worldwide safety experience. Labeling comments are reserved pending resolution of these core issues.
The proposed proprietary name was found conditionally acceptable. It must be resubmitted when all application deficiencies identified in this letter have been addressed.
Recommended response: Resubmit the proprietary name with the complete response, ensuring all other deficiencies are resolved.
A comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b), including data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level.
Recommended response: Prepare a comprehensive safety update in accordance with 21 CFR 314.50(d)(5)(vi)(b), covering all relevant studies.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Describe in detail any significant changes or findings in the safety profile.
Recommended response: Analyze and document all significant changes or new findings in the safety profile.
Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission. Present tabulations of the new safety data combined with the original application data. Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
Recommended response: Re-analyze and present all safety data, including new and original, in a comparative and consistent format.
For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
Recommended response: Generate and submit separate adverse event tables for all indications studied.
Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.
Recommended response: Update and analyze reasons for trial discontinuations, including data from newly completed trials, and identify new trends.
Provide case report forms and narrative summaries for each subject who died during a clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.
Recommended response: Compile and submit all requested case report forms and narrative summaries for deaths and serious adverse events.
Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.
Recommended response: Conduct a comparative analysis of common adverse event incidences between new and original data and report any substantial changes.
Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
Recommended response: Update and submit all clinical exposure data, including number of subjects and person-time.
Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.
Recommended response: Compile and summarize global safety data and usage estimates for the drug.
Provide English translations of current approved foreign labeling not previously submitted.
Recommended response: Obtain and submit English translations of all relevant current approved foreign labeling.
FDA reserves comment on the proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review labeling review resources.
Recommended response: Review FDA labeling resources and guidance documents in preparation for future labeling submissions.
The primary theme is the inadequacy of the safety data presentation and analysis, necessitating a thorough update and re-evaluation of clinical safety information, including global experience and detailed adverse event reporting. Labeling issues are secondary and contingent on resolving safety concerns.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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