Issued December 11, 2024
Issued
December 11, 2024
Application
NDA 505b1 • 212271
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) 212271. It outlines deficiencies and provides instructions for the applicant to address issues related to prescribing information, carton and container labeling, proprietary name, and safety updates. The letter also specifies requirements for resubmission.
The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, requiring comprehensive clinical data presentation, case report forms, worldwide safety experience, and updated exposure information. Additionally, there are requirements for resubmission of the proprietary name and English translations of foreign labeling. The agency reserved comment on proposed labeling until other deficiencies are addressed, but advised on format compliance.
The proposed proprietary name was found conditionally acceptable pending approval of the application. It must be resubmitted when responding to all application deficiencies.
Recommended response: Resubmit the proposed proprietary name as part of the complete response package addressing all deficiencies.
A comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This update must include data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level, and describe any significant changes or findings in the safety profile.
Recommended response: Compile and submit a comprehensive safety update, ensuring all required data elements are included and analyzed for significant changes in the safety profile across all studies.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
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 non-proposed indications from clinical trials to facilitate comprehensive safety review.
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. Additionally, provide narrative summaries for all serious adverse events.
Recommended response: Collect and submit all requested case report forms and narrative summaries for deaths, discontinuations due to adverse events, and all serious adverse events to support safety evaluation.
Provide updated exposure information for the clinical studies/trials, including details such as the number of subjects and person-time.
Recommended response: Update and submit all clinical exposure information, including subject numbers and person-time data, for all relevant studies.
Provide a summary of worldwide experience on the safety of this drug, including an updated estimate of use for the drug marketed in other countries.
Recommended response: Compile and submit a comprehensive summary of worldwide safety experience, including updated usage estimates from all markets where the drug is available.
Provide English translations of current approved foreign labeling not previously submitted.
Recommended response: Obtain and submit English translations of all current approved foreign labeling that has not yet been provided in the submission.
The agency reserves comment on the proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review labeling resources and use the SRPI checklist for format compliance. The response must include updated content of labeling in structured product labeling (SPL) format as described at FDA.gov, per 21 CFR 314.50(l)(1)(i).
Recommended response: Review and revise prescribing information according to FDA labeling resources and the SRPI checklist. Ensure all updated content is submitted in the required SPL format.
Cited: 21 CFR 314.50(l)(1)(i)
The agency reserves comment on the proposed carton and container labeling until the application is otherwise adequate.
Recommended response: Be prepared to revise carton and container labeling once the core application deficiencies are addressed and the agency provides specific comments.
Peer companies: Unknown
Historical frequency: 0 similar letters
The primary themes of the Complete Response Letter are the inadequacy of the safety data package, requiring more comprehensive clinical data, detailed case reports, and global safety summaries. There are also deficiencies related to labeling compliance and administrative requirements for resubmission.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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