Complete Response Letter BLA 761376 (Apr 19, 2024)

Summary

This document is a Complete Response Letter (CRL) from the FDA regarding Biologics License Application (BLA) 761376. It outlines deficiencies that prevent approval and provides instructions for resubmission, including requirements for a safety update, proprietary name resubmission, and labeling considerations. Several sections detailing product quality, microbiology, drug substance, and drug product deficiencies are redacted.

Key points

• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI).
• Review the FDA guidance for industry Labeling for Biosimilar Products.
• Resubmit the proposed proprietary name when responding to all application deficiencies.
• Include a safety update with data from all nonclinical and clinical studies of the product under consideration, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.
• Present new safety data from the 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.

Cited reasons

• Inadequate Safety Update and Data Presentation
• Missing Case Report Forms and Serious Adverse Event Narratives
• Incomplete Worldwide Safety Experience and Foreign Labeling Translations
• Proprietary Name Resubmission Required
• The FDA issued a Complete Response Letter for BLA 761376, primarily due to significant deficiencies in the safety update and data presentation. The agency requires a comprehensive safety update, including detailed clinical and nonclinical safety data, case report forms for adverse events, and a summary of worldwide safety experience. Additionally, the proprietary name, though conditionally acceptable, must be resubmitted after all deficiencies are addressed. The letter also notes the need for English translations of foreign labeling. While product quality sections were present, specific approvability issues were redacted or noted as non-approvability comments.

Recommended actions

• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI).
• Review the FDA guidance for industry Labeling for Biosimilar Products.
• Resubmit the proposed proprietary name when responding to all application deficiencies.
• Include a safety update with data from all nonclinical and clinical studies of the product under consideration, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.
• Present new safety data from the 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.

Deficiency summary

The FDA issued a Complete Response Letter for BLA 761376, primarily due to significant deficiencies in the safety update and data presentation. The agency requires a comprehensive safety update, including detailed clinical and nonclinical safety data, case report forms for adverse events, and a summary of worldwide safety experience. Additionally, the proprietary name, though conditionally acceptable, must be resubmitted after all deficiencies are addressed. The letter also notes the need for English translations of foreign labeling. While product quality sections were present, specific approvability issues were redacted or noted as non-approvability comments.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme of this Complete Response Letter is the critical need for a comprehensive and updated safety data package, including detailed clinical and nonclinical information, case reports, and worldwide experience. Additionally, administrative and labeling aspects, such as proprietary name resubmission and foreign labeling translations, require attention. The agency emphasizes that all deficiencies must be fully addressed for resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%