Complete Response Letter BLA 761308 (Mar 20, 2025)

Summary

This FDA letter addresses deficiencies in Biologics License Application (BLA) 761308, providing detailed instructions for revising labeling, updating safety information, and resubmitting the application. It outlines specific requirements for content, format, and timelines to achieve potential approval, emphasizing that the product cannot be marketed until written approval is received.

Key points

• Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
• Add the bolded statement "ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide" or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name when responding to all application deficiencies.
• 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 drug under consideration, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile within the safety update.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.

Cited reasons

• Medication Guide Statement on Labeling
• Proprietary Name Resubmission
• Comprehensive Safety Update Required
• Detailed Description of Safety Profile Changes
• Incorporation of New Safety Data into AE Sections
• Separate AE Tables for Other Indications
• Retabulation of Premature Trial Discontinuations
• Case Report Forms and Narratives for Deaths/SAEs

Recommended actions

• Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
• Add the bolded statement "ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide" or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name when responding to all application deficiencies.
• 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 drug under consideration, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile within the safety update.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.

Deficiency summary

The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, requiring comprehensive clinical data analysis, adverse event reporting, and worldwide experience summary. Minor issues with labeling and proprietary name resubmission were also 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 of the Complete Response Letter is the inadequacy of the safety profile data, requiring extensive updates and detailed analysis of clinical trial results, adverse events, and global safety experience, alongside minor labeling and administrative corrections.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%