Complete Response Letter NDA 505b1 218506 (Jun 13, 2024)

Summary

This document is a Complete Response Letter (CRL) from the FDA for New Drug Application (NDA) 218506, outlining deficiencies that prevent approval in its current form. It addresses issues related to product quality, proprietary name, facility inspections, and requires a comprehensive safety update.

Key points

• The applicant must provide satisfactory responses to the deficiencies conveyed by the FDA following a pre-approval inspection of the manufacturing facility.
• The applicant must include the date(s) of the facility’s response(s) to the FDA Form 483 in their complete response.
• The applicant must resubmit the proposed proprietary name when responding to all application deficiencies.
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to the deficiencies.
• The safety update must include data from all nonclinical and clinical studies/trials of the product under consideration, regardless of indication, dosage form, or dose level.
• The applicant must describe in detail any significant changes or findings in the safety profile.
• The applicant must 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.
• The applicant must present tabulations of new safety data combined with original application data.

Cited reasons

• Unresolved Facility Inspection Deficiencies
• Proprietary Name Resubmission Required
• Comprehensive Safety Update Required
• The FDA issued a Complete Response Letter for NDA 218506 due to significant deficiencies identified during a facility inspection, requiring satisfactory responses prior to resubmission. Additionally, the proposed proprietary name, though conditionally acceptable, needs resubmission with the complete response. A comprehensive safety update, including detailed data analyses and case report forms, is also required as per regulatory guidelines.

Recommended actions

• The applicant must provide satisfactory responses to the deficiencies conveyed by the FDA following a pre-approval inspection of the manufacturing facility.
• The applicant must include the date(s) of the facility’s response(s) to the FDA Form 483 in their complete response.
• The applicant must resubmit the proposed proprietary name when responding to all application deficiencies.
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to the deficiencies.
• The safety update must include data from all nonclinical and clinical studies/trials of the product under consideration, regardless of indication, dosage form, or dose level.
• The applicant must describe in detail any significant changes or findings in the safety profile.
• The applicant must 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.
• The applicant must present tabulations of new safety data combined with original application data.

Deficiency summary

The FDA issued a Complete Response Letter for NDA 218506 due to significant deficiencies identified during a facility inspection, requiring satisfactory responses prior to resubmission. Additionally, the proposed proprietary name, though conditionally acceptable, needs resubmission with the complete response. A comprehensive safety update, including detailed data analyses and case report forms, is also required as per regulatory guidelines.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

270 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes of this Complete Response Letter are critical manufacturing and quality system deficiencies identified during a facility inspection, administrative requirements for proprietary name resubmission, and the need for a thorough and updated clinical safety data analysis to meet regulatory standards.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%