US FDA•United StatesCRL•Complete Response Letter

Complete Response Letter NDA 505b1 215291 (Jan 17, 2024)

Issued January 17, 2024

Issued

January 17, 2024

Application

NDA 505b1 • 215291

Review center

CDER

Stage

Final Decision

Letter type

Complete Response Letter

Response due January 16, 2025Requires resubmission addressing deficiencies.

Summary

This FDA letter for NDA 215291 outlines deficiencies that must be resolved before the application can be approved. It provides detailed requirements for labeling revisions, proprietary name resubmission, and a comprehensive safety update, including specific data presentation formats for clinical trial safety information. It also sets a one-year deadline for resubmission or other actions and advises on meeting requests.

Key points

Satisfactorily resolve all identified deficiencies before the application may be approved.
Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the Selected Requirements for Prescribing Information (SRPI) checklist.
If revising labeling, use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
Resubmit the proposed proprietary name when responding to all application deficiencies.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
The safety update must include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.
Describe in detail any significant changes or findings in the safety profile.

Cited reasons

Comprehensive Safety Update Required
Prescribing Information Adequacy
Carton and Container Labeling Adequacy
Proprietary Name Resubmission
The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, requiring comprehensive data analysis, detailed reporting of adverse events, and updated exposure information across all studies. Additionally, comments on prescribing information and carton/container labeling are reserved until the application is otherwise adequate, and the proprietary name requires resubmission with the complete response.

Recommended actions

Satisfactorily resolve all identified deficiencies before the application may be approved.
Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the Selected Requirements for Prescribing Information (SRPI) checklist.
If revising labeling, use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
Resubmit the proposed proprietary name when responding to all application deficiencies.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
The safety update must include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.
Describe in detail any significant changes or findings in the safety profile.

Deficiency summary

The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, requiring comprehensive data analysis, detailed reporting of adverse events, and updated exposure information across all studies. Additionally, comments on prescribing information and carton/container labeling are reserved until the application is otherwise adequate, and the proprietary name requires resubmission with the complete response.

Findings

Comprehensive Safety Update Required

Severity: critical

A complete safety update is required, including data from all nonclinical and clinical studies regardless of indication, dosage form, or dose level. This involves describing significant changes, incorporating new safety data (tabulations, comparisons), retabulating premature discontinuations, providing case report forms and narrative summaries for deaths/SAEs, describing changes in common AEs, providing updated exposure information, summarizing worldwide safety experience, and providing English translations of foreign labeling.

Recommended response: Conduct a thorough safety update across all studies. Provide detailed analyses, tabulations, narratives, and exposure data. Ensure all foreign labeling is translated and submitted.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Prescribing Information Adequacy

Severity: major

FDA reserves comment on proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review labeling resources and the SRPI checklist. Updated content of labeling in structured product labeling (SPL) format is required.

Recommended response: Revise prescribing information to conform with regulations and guidances, using the SRPI checklist. Submit updated content in SPL format.

Cited: 21 CFR 314.50(l)(1)(i)

Carton and Container Labeling Adequacy

Severity: major

FDA reserves comment on the proposed carton and container labeling until the application is otherwise adequate.

Recommended response: Ensure carton and container labeling is consistent with the revised prescribing information and regulatory requirements once the application is otherwise adequate.

Proprietary Name Resubmission

Severity: minor

The proposed proprietary name was found conditionally acceptable but needs to be resubmitted when all application deficiencies have been addressed.

Recommended response: Resubmit the proprietary name application concurrently with the complete response to all other deficiencies.

Regulatory context

Submission stage: final decision
Regulatory pathway: NDA

Impact

Impact score: 0.95
Estimated delay: 365 days
Estimated rework cost: $0
Subsequent action: resubmission

Strategic insights

The primary theme of the Complete Response Letter is the inadequacy of the safety data update, requiring extensive additional clinical and nonclinical safety information and analysis. Labeling comments are deferred pending resolution of these core deficiencies, and the proprietary name requires resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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