Approval Letter Other 210136 (Jan 1, 2024)

Summary

This is a Complete Response letter from the FDA to Braeburn Inc. for their New Drug Application (NDA) 210136 for BRIXADI (buprenorphine) extended-release injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, prescribing information, proprietary name resubmission, safety update requirements, and mandated postmarketing studies.

Key points

• Satisfactorily resolve deficiencies identified during facility inspections of Pharmaceutics International manufacturing, testing, and warehouse facilities.
• Submit draft labeling responsive to the electronic communication dated December 15, 2021.
• Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
• Submit updated content of labeling (21 CFR 314.50(l)(1)(i)) in structured product labeling (SPL) format.
• Provide a highlighted or marked-up copy showing all changes and a clean Word version of the labeling, with annotations supporting proposed changes.
• Ensure the proposed Prescribing Information (PI) conforms to content and format regulations at 21 CFR 201.56(a) and (d) and 201.57.
• Resubmit the proposed proprietary name, BRIXADI, when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies, detailing significant changes, presenting new and combined safety data, retabulating reasons for premature trial discontinuation, providing case report forms and narrative summaries for deaths/serious adverse events, describing changes in common adverse events, providing updated exposure information, summarizing worldwide safety experience, and providing English translations of current approved foreign labeling.

Cited reasons

• Unsatisfactory Resolution of Facility Inspection Deficiencies
• Inadequate Prescribing Information and Formatting
• Resubmission of Proprietary Name Required
• Comprehensive Safety Update Required
• Postmarketing Study Requirements Identified
• The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, inadequate prescribing information requiring updates and formatting corrections, the need to resubmit the proprietary name, and the requirement for a comprehensive safety update. Postmarketing study requirements were also outlined.

Recommended actions

• Satisfactorily resolve deficiencies identified during facility inspections of Pharmaceutics International manufacturing, testing, and warehouse facilities.
• Submit draft labeling responsive to the electronic communication dated December 15, 2021.
• Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
• Submit updated content of labeling (21 CFR 314.50(l)(1)(i)) in structured product labeling (SPL) format.
• Provide a highlighted or marked-up copy showing all changes and a clean Word version of the labeling, with annotations supporting proposed changes.
• Ensure the proposed Prescribing Information (PI) conforms to content and format regulations at 21 CFR 201.56(a) and (d) and 201.57.
• Resubmit the proposed proprietary name, BRIXADI, when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies, detailing significant changes, presenting new and combined safety data, retabulating reasons for premature trial discontinuation, providing case report forms and narrative summaries for deaths/serious adverse events, describing changes in common adverse events, providing updated exposure information, summarizing worldwide safety experience, and providing English translations of current approved foreign labeling.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, inadequate prescribing information requiring updates and formatting corrections, the need to resubmit the proprietary name, and the requirement for a comprehensive safety update. Postmarketing study requirements were also outlined.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) of the Federal Food, Drug, and Cosmetic Act

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing site deficiencies, significant labeling issues requiring comprehensive updates and formatting, and the need for a thorough safety data update. The agency also outlined specific postmarketing study requirements for approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%