Issued December 23, 2024
Issued
December 23, 2024
Application
NDA 505b1 • 219357
Review center
CDER
Stage
Final Decision
Letter type
Complete Response Letter
This FDA letter addresses deficiencies in New Drug Application (NDA) 219357, providing instructions for the applicant to resubmit the application. Key areas of focus include labeling, proprietary name, and a comprehensive safety update, along with general resubmission requirements and timelines.
The application received a Complete Response due to significant deficiencies in the safety update, including inadequate presentation of clinical safety data, missing worldwide safety experience, and lack of English translations for foreign labeling. Labeling comments are reserved pending resolution of these issues.
The proposed proprietary name was found conditionally acceptable but requires resubmission when all application deficiencies are addressed.
Recommended response: Resubmit the proprietary name application concurrently with the complete response to all other deficiencies.
A comprehensive safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), is required. This includes data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level.
Recommended response: Compile and submit a complete safety update covering all required aspects as per regulatory guidelines.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Deficiencies in presenting clinical safety data include: describing significant changes in safety profile; incorporating new safety data into discontinuations, SAEs, and common AEs sections; presenting new safety data in the same format as original submission; tabulating new data combined with original data; comparing frequencies of AEs; providing separate tables for AEs in clinical trials for other indications; retabulating reasons for premature trial discontinuation; describing new trends; providing case report forms and narrative summaries for deaths/discontinuations due to AEs and for serious AEs; describing changes in common, less serious AEs; and providing updated exposure information.
Recommended response: Thoroughly review and re-present all clinical safety data, ensuring all specified elements are addressed, formatted correctly, and include comprehensive narratives and forms.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
A summary of worldwide experience on the safety of this drug, including an updated estimate of use for drug marketed in other countries, is required.
Recommended response: Gather and compile all available worldwide safety data and usage estimates, presenting them in a comprehensive summary.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
English translations of current approved foreign labeling not previously submitted are required.
Recommended response: Obtain and submit certified English translations for all relevant foreign labeling.
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 potential future labeling comments based on the updated application.
The primary themes are insufficient clinical safety data and documentation, requiring a comprehensive safety update and proper presentation of global safety information before approval can be considered.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 25%
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