Issued June 27, 2025
Issued
June 27, 2025
Application
NDA 505b1 • 218607
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) 218607. It outlines deficiencies in the application concerning prescribing information, carton and container labeling, proprietary name, and safety updates. The letter provides detailed instructions for addressing these deficiencies, particularly for the safety update, and sets a one-year deadline for resubmission or other actions.
The application received a Complete Response Letter primarily due to significant deficiencies in the clinical safety data presentation, including missing case report forms, narrative summaries for serious adverse events and deaths, and inadequate worldwide safety experience summaries. The agency also requires updated exposure information, retabulation of discontinuations, and English translations of foreign labeling. Labeling comments are reserved until these core issues are resolved.
The proposed proprietary name was found conditionally acceptable pending approval of the application. Please resubmit the proposed proprietary name when all application deficiencies have been addressed.
Recommended response: Re-submit the proprietary name application with the complete response to all deficiencies.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level. Describe in detail any significant changes or findings in the safety profile.
Recommended response: Prepare a comprehensive safety update incorporating all new nonclinical and clinical data, highlighting any significant changes in the safety profile.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Present new safety data from the 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: Reformat and present new safety data clearly, combining it with original data and providing comparative tables of adverse event frequencies.
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 frequency 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 retabulate premature discontinuation data, analyzing and reporting any new trends or patterns identified.
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, discontinuations due to adverse events, and all 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 an analysis to identify and describe any significant changes in the incidence of common, less serious adverse events between new and original data.
Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
Recommended response: Update and submit all clinical exposure information, including subject numbers and person-time data.
Provide a summary of worldwide experience on the safety of this product. Include an updated estimate of use for product marketed in other countries.
Recommended response: Compile and submit a comprehensive summary of global safety experience and updated usage estimates for the product marketed in other countries.
Provide English translations of current approved foreign labeling not previously submitted.
Recommended response: Obtain and submit English translations for all relevant foreign approved labeling not yet provided.
Comments on the proposed prescribing information and carton and container labeling are reserved until the application is otherwise adequate.
Recommended response: Address all other deficiencies first, then prepare for labeling negotiations once the application is deemed adequate.
The primary theme is the inadequacy and incomplete nature of the safety data package, particularly regarding clinical trial adverse events, global safety experience, and supporting documentation, which prevents a full assessment of the product's safety profile.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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