Complete Response Letter NDA 505b1 218528 (Jan 25, 2024)

Summary

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218528. It outlines specific requirements and recommendations concerning prescribing information, carton and container labeling, medication guides, proprietary name resubmission, and a comprehensive safety update. The letter also includes additional Chemistry, Manufacturing, and Controls (CMC) comments.

Key points

• The proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name when responding to all identified 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.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication in the same format as the original submission.
• Present tabulations of new safety data combined with original application data.

Cited reasons

• Medication Guide Statement on Labeling
• Proprietary Name Resubmission
• Comprehensive Safety Update Required
• Separate AE Tables for Other Indications
• Case Report Forms and Narrative Summaries for Deaths/SAEs
• Updated Clinical Exposure Data
• Worldwide Safety Experience Summary
• English Translations of Foreign Labeling

Recommended actions

• The proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name when responding to all identified 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.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication in the same format as the original submission.
• Present tabulations of new safety data combined with original application data.

Deficiency summary

The application received a Complete Response Letter primarily due to significant deficiencies in clinical safety data presentation, comprehensive safety updates, and various labeling requirements. Additionally, there are CMC comments that, while not approvability issues for this letter, must be addressed in the resubmission. Key issues include missing adverse event tables, case report forms, updated exposure data, worldwide safety summaries, and foreign labeling translations, alongside specific medication guide and proprietary name issues.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

180 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes of this Complete Response Letter are the need for a comprehensive and updated safety profile, including detailed clinical data presentation and worldwide experience, and significant revisions to labeling to meet regulatory content and format requirements. Minor CMC recommendations also need to be addressed.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%