Complete Response Letter BLA 761357 (Mar 26, 2024)

Summary

This letter from the FDA addresses deficiencies in a Biologics License Application (BLA 761357) and outlines requirements for its resubmission. It covers facility inspections, prescribing information, proprietary name, and a detailed safety update, emphasizing that the product cannot be marketed until approved.

Key points

• The BLA resubmission must include the date of the facility’s response to the FDA Form 483.
• The applicant must work with the facility to resolve related inspection deficiencies.
• If labeling is revised, the applicant must use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
• The response must include updated content of labeling in structured product labeling (SPL) format.
• The proposed proprietary name must be resubmitted when all application deficiencies identified in this letter are addressed.
• The resubmission must include a safety update with data from all nonclinical and clinical studies of the product.
• The safety update must describe any significant changes or findings in the safety profile and their relevance to differences between the proposed biosimilar product and the U.S.-licensed reference product.
• The safety update must present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.

Cited reasons

• Unresolved Facility Inspection Deficiencies
• Proprietary Name Resubmission Required
• Inadequate Safety Update - Significant Changes and Biosimilarity Relevance
• Inadequate Safety Update - Data Presentation and Analysis
• Missing Case Report Forms and Narrative Summaries for Safety Events
• The FDA issued a Complete Response Letter for BLA 761357 due to unresolved manufacturing facility inspection deficiencies, the need to resubmit the proprietary name, and significant issues with the completeness and presentation of safety data. Key deficiencies include the lack of detailed safety updates regarding significant changes and their relevance to biosimilarity, inadequate presentation of combined new and original safety data, and missing case report forms and narrative summaries for deaths and serious adverse events.

Recommended actions

• The BLA resubmission must include the date of the facility’s response to the FDA Form 483.
• The applicant must work with the facility to resolve related inspection deficiencies.
• If labeling is revised, the applicant must use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
• The response must include updated content of labeling in structured product labeling (SPL) format.
• The proposed proprietary name must be resubmitted when all application deficiencies identified in this letter are addressed.
• The resubmission must include a safety update with data from all nonclinical and clinical studies of the product.
• The safety update must describe any significant changes or findings in the safety profile and their relevance to differences between the proposed biosimilar product and the U.S.-licensed reference product.
• The safety update must present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.

Deficiency summary

The FDA issued a Complete Response Letter for BLA 761357 due to unresolved manufacturing facility inspection deficiencies, the need to resubmit the proprietary name, and significant issues with the completeness and presentation of safety data. Key deficiencies include the lack of detailed safety updates regarding significant changes and their relevance to biosimilarity, inadequate presentation of combined new and original safety data, and missing case report forms and narrative summaries for deaths and serious adverse events.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA (Biosimilar)

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes of this Complete Response Letter are significant deficiencies in manufacturing facility compliance and comprehensive clinical safety data reporting, particularly concerning the demonstration of biosimilarity and the detailed presentation of adverse event information. The agency requires a thorough re-evaluation and resubmission addressing these core issues before approval can be considered.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%