Complete Response Letter BLA 761424 (Mar 13, 2025)

Summary

This FDA letter, identified as BLA 761424, outlines deficiencies in a Biologics License Application and provides detailed instructions for resubmission. It specifies requirements for updating prescribing information (labeling) to conform with regulations and guidances, and mandates a comprehensive safety update incorporating new clinical data, worldwide experience, and foreign labeling translations.

Key points

• Submit draft labeling responsive to the electronic communication.
• Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
• Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov.
• Provide a highlighted or marked-up copy of the labeling showing all changes, along with a clean Word version.
• Include annotations in the marked-up copy to support any proposed labeling changes.
• Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
• Include a safety update when responding to the deficiencies.
• Describe in detail any significant changes or findings in the safety profile and their relevance to potential clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.

Cited reasons

• Inadequate Prescribing Information (PI) Content and Format
• Insufficient Safety Data Update and Presentation
• Missing English Translations for Foreign Labeling
• The FDA issued a Complete Response Letter for BLA 761424, citing significant deficiencies primarily related to the content and format of the Prescribing Information (PI) and the completeness and presentation of safety data. The agency requires a comprehensive safety update, including detailed clinical and nonclinical data, case report forms, and worldwide experience. Additionally, the PI must be revised to conform to regulatory standards, including proper formatting, SPL submission, and provision of English translations for foreign labeling.

Recommended actions

• Submit draft labeling responsive to the electronic communication.
• Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
• Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov.
• Provide a highlighted or marked-up copy of the labeling showing all changes, along with a clean Word version.
• Include annotations in the marked-up copy to support any proposed labeling changes.
• Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
• Include a safety update when responding to the deficiencies.
• Describe in detail any significant changes or findings in the safety profile and their relevance to potential clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.

Deficiency summary

The FDA issued a Complete Response Letter for BLA 761424, citing significant deficiencies primarily related to the content and format of the Prescribing Information (PI) and the completeness and presentation of safety data. The agency requires a comprehensive safety update, including detailed clinical and nonclinical data, case report forms, and worldwide experience. Additionally, the PI must be revised to conform to regulatory standards, including proper formatting, SPL submission, and provision of English translations for foreign labeling.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.75

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The Complete Response Letter highlights critical deficiencies in both the labeling content/format and the comprehensive safety data package, indicating that the application is not approvable in its current state. Key themes include non-compliance with PI regulations, inadequate safety data presentation, and missing administrative documents.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%