Approval Letter Other 215000 (Jan 1, 2022)

Summary

This document is a Complete Response letter from the FDA to Accord Healthcare, Inc. regarding their New Drug Application (NDA) 215000 for Carmustine for injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality, prescribing information, and safety updates. The letter outlines specific actions required for resubmission.

Key points

• Conduct a leachable study using conditions that represent the worst-case scenario (aged samples under long-term and accelerated conditions).
• Justify the proposed AET and PDE.
• Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• 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 in the safety update.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.

Cited reasons

• Product Quality Deficiencies
• Inadequate Prescribing Information
• Incomplete Safety Update and Clinical Data
• The application for Carmustine for injection cannot be approved in its present form due to significant product quality issues, inadequate clinical safety data, and pending revisions to the prescribing information. A comprehensive resubmission addressing all identified deficiencies is required.

Recommended actions

• Conduct a leachable study using conditions that represent the worst-case scenario (aged samples under long-term and accelerated conditions).
• Justify the proposed AET and PDE.
• Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• 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 in the safety update.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.

Deficiency summary

The application for Carmustine for injection cannot be approved in its present form due to significant product quality issues, inadequate clinical safety data, and pending revisions to the prescribing information. A comprehensive resubmission addressing all identified deficiencies is required.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2)

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response Letter due to unresolved product quality issues, substantial deficiencies in clinical safety data reporting and analysis, and the need for updated prescribing information. A full resubmission addressing these critical areas is required for potential approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%