Complete Response Letter BLA 761290 (Jan 31, 2025)

Summary

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding Biologics License Application (BLA) 761290. It outlines deficiencies and provides instructions for resubmission, including requirements for labeling, proprietary name, and a comprehensive safety update. The letter also specifies the timeline and format for resubmission and notes that the product cannot be marketed until approved.

Key points

• The applicant must resubmit the proposed proprietary name when all application deficiencies identified in this letter have been addressed.
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• The safety update must include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level.
• The safety update must describe in detail any significant changes or findings in the safety profile.
• The safety update must incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication using the same format as the original submission.
• The safety update must present tabulations of new safety data combined with original application data.
• The safety update must include tables comparing frequencies of adverse events in the original application with retabulated frequencies.
• For indications other than the proposed indication, the safety update must provide separate tables for the frequencies of adverse events occurring in clinical trials.

Cited reasons

• Proprietary Name Resubmission Required
• Comprehensive Safety Update Required
• Separate AE Tables for Other Indications
• Missing Case Report Forms and Narrative Summaries for Deaths/SAEs
• Updated Clinical Exposure Information Required
• Worldwide Safety Experience Summary Required
• English Translations of Foreign Labeling Required
• The FDA issued a Complete Response Letter due to significant deficiencies primarily related to the clinical safety data package, including incomplete adverse event reporting, missing case report forms, insufficient exposure information, and lack of a comprehensive worldwide safety summary. Additionally, administrative issues such as proprietary name resubmission and untranslated foreign labeling were noted.

Recommended actions

• The applicant must resubmit the proposed proprietary name when all application deficiencies identified in this letter have been addressed.
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• The safety update must include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level.
• The safety update must describe in detail any significant changes or findings in the safety profile.
• The safety update must incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication using the same format as the original submission.
• The safety update must present tabulations of new safety data combined with original application data.
• The safety update must include tables comparing frequencies of adverse events in the original application with retabulated frequencies.
• For indications other than the proposed indication, the safety update must provide separate tables for the frequencies of adverse events occurring in clinical trials.

Deficiency summary

The FDA issued a Complete Response Letter due to significant deficiencies primarily related to the clinical safety data package, including incomplete adverse event reporting, missing case report forms, insufficient exposure information, and lack of a comprehensive worldwide safety summary. Additionally, administrative issues such as proprietary name resubmission and untranslated foreign labeling were noted.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme is the inadequacy and incompleteness of the clinical safety data package, which prevents approval. Key issues include insufficient adverse event reporting, missing detailed patient data (CRFs, narratives), and a lack of comprehensive global safety information. Administrative items also need to be addressed.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%