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US FDA•United StatesCRL•Complete Response Letter

Complete Response Letter NDA 505b1 218026 (Aug 16, 2024)

Issued August 16, 2024

Issued

August 16, 2024

Application

NDA 505b1 • 218026

Review center

CDER

Stage

Final Decision

Letter type

Complete Response Letter

Response due August 16, 2025Requires resubmission addressing deficiencies.

Summary

This FDA letter outlines deficiencies for New Drug Application (NDA) 218026 and provides detailed instructions for resubmission, focusing on labeling requirements, safety updates, and administrative procedures.

Key points

  • Provide a highlighted or marked-up copy showing all changes and a clean Word version of the submission.
  • Include annotations in the marked-up copy to support any proposed changes.
  • Ensure the proposed Prescribing Information (PI) conforms to 21 CFR 201.56(a) and (d) and 201.57.
  • Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
  • 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.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.

Cited reasons

  • Prescribing Information (PI) Format and Content Non-Compliance
  • Proprietary Name Resubmission Required
  • Inadequate Safety Update Submission
  • The application received a Complete Response Letter primarily due to deficiencies in the format and content of the Prescribing Information (PI), the need for resubmission of the proprietary name, and significant issues with the submitted safety update, requiring comprehensive new data and analyses.

Recommended actions

  • Provide a highlighted or marked-up copy showing all changes and a clean Word version of the submission.
  • Include annotations in the marked-up copy to support any proposed changes.
  • Ensure the proposed Prescribing Information (PI) conforms to 21 CFR 201.56(a) and (d) and 201.57.
  • Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
  • 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.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.

Deficiency summary

The application received a Complete Response Letter primarily due to deficiencies in the format and content of the Prescribing Information (PI), the need for resubmission of the proprietary name, and significant issues with the submitted safety update, requiring comprehensive new data and analyses.

Findings

Prescribing Information (PI) Format and Content Non-Compliance

Severity: major

The proposed Prescribing Information (PI) does not conform to the content and format regulations specified in 21 CFR 201.56(a), 201.56(d), and 201.57. A marked-up copy showing all changes and a clean Word version of the revised PI are also required to facilitate review.

Recommended response: Revise the Prescribing Information to fully comply with 21 CFR 201.56(a), (d), and 201.57. Provide both a marked-up copy highlighting all changes and a clean Word version of the updated PI.

Cited: 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57

Proprietary Name Resubmission Required

Severity: minor

The proposed proprietary name was found conditionally acceptable pending approval of the application. It must be resubmitted when all application deficiencies identified in this letter have been addressed.

Recommended response: Resubmit the proposed proprietary name along with the complete response to all application deficiencies.

Inadequate Safety Update Submission

Severity: critical

A comprehensive safety update is required as described in 21 CFR 314.50(d)(5)(vi)(b). This includes detailing significant changes in the safety profile, presenting new safety data from studies (including tabulations and comparisons), providing case report forms and narrative summaries for deaths/serious adverse events, updating exposure information, summarizing worldwide safety experience, and providing English translations of current approved foreign labeling.

Recommended response: Provide a comprehensive safety update addressing all specified requirements under 21 CFR 314.50(d)(5)(vi)(b), including detailed adverse event data, case narratives, exposure updates, and worldwide safety information.

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

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 themes of the Complete Response Letter are non-compliance with labeling regulations for Prescribing Information, the need to resubmit the proprietary name, and significant deficiencies in the safety update data and analysis required for the application.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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