Complete Response Letter BLA 761266 (Jan 3, 2025)

Summary

This document outlines specific requirements and recommendations for a Biologics License Application (BLA) for a biosimilar product, focusing on the submission of updated safety data, labeling information, and proprietary name details. It emphasizes compliance with FDA regulations and guidance for biosimilar products.

Key points

• Compare the proposed biosimilar product with the U.S.-licensed reference product.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
• Present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.
• Present tabulations of the new safety data combined with the original BLA data.
• Include tables that compare frequencies of adverse events in the original BLA with the retabulated frequencies.
• Present a retabulation of the reasons for premature study discontinuation by incorporating drop-outs from newly completed studies.
• Describe any new trends or patterns identified in premature study discontinuation.
• Provide case report forms and narrative summaries for each subject who died during a clinical study or who did not complete a study because of an adverse event.

Cited reasons

• Inadequate Clinical Safety Data Presentation and Retabulation
• Missing Case Report Forms and Narrative Summaries for Deaths and Serious Adverse Events
• Insufficient Updated Clinical Exposure Information
• Incomplete Worldwide Safety Experience Summary
• Missing English Translations of Approved Foreign Labeling
• Non-compliant Prescribing Information (PI)
• Non-compliant Carton and Container Labeling
• Proprietary Name Requires Resubmission

Recommended actions

• Compare the proposed biosimilar product with the U.S.-licensed reference product.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
• Present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.
• Present tabulations of the new safety data combined with the original BLA data.
• Include tables that compare frequencies of adverse events in the original BLA with the retabulated frequencies.
• Present a retabulation of the reasons for premature study discontinuation by incorporating drop-outs from newly completed studies.
• Describe any new trends or patterns identified in premature study discontinuation.
• Provide case report forms and narrative summaries for each subject who died during a clinical study or who did not complete a study because of an adverse event.

Deficiency summary

The FDA issued a Complete Response Letter for BLA 761266, citing significant deficiencies primarily related to clinical safety data presentation, comprehensive safety reporting (including worldwide experience and adverse event narratives), and multiple aspects of product labeling (Prescribing Information, carton/container, and proprietary name). The agency requires updated and reformatted clinical safety data, detailed adverse event narratives, English translations of foreign labeling, and revised labeling conforming to regulatory requirements and guidances. The proprietary name is conditionally acceptable pending resolution of all application deficiencies.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

180 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes of the Complete Response Letter are the need for comprehensive and properly formatted clinical safety data, including detailed adverse event reporting and worldwide experience, and significant revisions to all aspects of product labeling to ensure regulatory compliance and clarity.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%