Complete Response Letter BLA 7613032 (Mar 22, 2024)

Summary

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding deficiencies found in their Biologics License Application (BLA) 761303/Original 2. It outlines specific requirements for addressing issues related to clinical trial completion, prescribing information, proprietary name, and safety updates, which must be fulfilled for a successful resubmission. The letter also provides guidance on the resubmission process and timelines.

Key points

• Address the deficiency regarding insufficient assurance of timely completion of the trial.
• Request a meeting with the Agency to discuss trial benchmarks (e.g., enrollment goals, site activation, proportion of primary endpoint events accrued, trial completion date) after enrollment and analysis of Part 1 (dose-finding) is completed.
• Demonstrate in the submission that milestones are appropriate and that sufficient progress in the conduct of the confirmatory portion of the confirmatory trial will be demonstrated prior to approval.
• 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) checklist.
• Use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling (21 CFR 601.14(b)) in structured product labeling (SPL) format if labeling is revised.
• Resubmit the proposed proprietary name after responding to all application deficiencies identified in this letter.
• Include a safety update as described at 21 CFR 601.2 when responding to deficiencies.

Cited reasons

• Insufficient Assurance of Timely Confirmatory Trial Completion
• Comprehensive Safety Update Required
• Proprietary Name Resubmission Required
• Labeling Comments Reserved; SPL Update Required
• The FDA issued a Complete Response Letter for BLA 761303/Original 2, citing insufficient assurance regarding the timely completion of the confirmatory clinical trial and requiring a comprehensive safety update. Additionally, comments on labeling are reserved until other deficiencies are addressed, and the proprietary name needs resubmission with the complete response.

Recommended actions

• Address the deficiency regarding insufficient assurance of timely completion of the trial.
• Request a meeting with the Agency to discuss trial benchmarks (e.g., enrollment goals, site activation, proportion of primary endpoint events accrued, trial completion date) after enrollment and analysis of Part 1 (dose-finding) is completed.
• Demonstrate in the submission that milestones are appropriate and that sufficient progress in the conduct of the confirmatory portion of the confirmatory trial will be demonstrated prior to approval.
• 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) checklist.
• Use the SRPI checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling (21 CFR 601.14(b)) in structured product labeling (SPL) format if labeling is revised.
• Resubmit the proposed proprietary name after responding to all application deficiencies identified in this letter.
• Include a safety update as described at 21 CFR 601.2 when responding to deficiencies.

Deficiency summary

The FDA issued a Complete Response Letter for BLA 761303/Original 2, citing insufficient assurance regarding the timely completion of the confirmatory clinical trial and requiring a comprehensive safety update. Additionally, comments on labeling are reserved until other deficiencies are addressed, and the proprietary name needs resubmission with the complete response.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes are the need for stronger assurance regarding the timely completion of the confirmatory clinical trial and a comprehensive update of safety data. Labeling comments are pending resolution of these core issues.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%