Assyro AI
US FDA•United StatesCRL•Complete Response Letter

Complete Response Letter BLA 761393 (Mar 11, 2025)

Issued March 11, 2025

Issued

March 11, 2025

Application

BLA • 761393

Review center

CBER

Stage

Final Decision

Letter type

Complete Response Letter

Response due March 11, 2026Requires resubmission addressing deficiencies.

Summary

This document is a deficiency letter from the FDA regarding Biologics License Application (BLA) 761393. It outlines deficiencies related to product quality, prescribing information, proprietary name, and requires a comprehensive safety update upon resubmission. The letter also provides instructions for resubmission and potential next steps.

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) checklist, prior to resubmitting the proposed package insert.
  • Resubmit the proposed proprietary name when all application deficiencies identified in this letter have been addressed.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to the deficiencies.
  • Describe in detail any significant changes or findings in the safety profile in the safety update.
  • 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 in the same format as the original submission.
  • Present tabulations of new safety data combined with original application data.
  • Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
  • Provide separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Cited reasons

  • Inadequate Prescribing Information
  • Proprietary Name Review Terminated
  • Insufficient Safety Update (General)
  • Inadequate Clinical Safety Data Presentation
  • Insufficient Worldwide Safety Experience Summary
  • Missing English Translations of Foreign Labeling
  • The application received a Complete Response due to significant deficiencies primarily related to the comprehensive safety update requirements, including detailed clinical data presentation, worldwide experience summary, and foreign labeling translations. Additionally, issues with proposed prescribing information and proprietary name review termination contributed to the decision.

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) checklist, prior to resubmitting the proposed package insert.
  • Resubmit the proposed proprietary name when all application deficiencies identified in this letter have been addressed.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to the deficiencies.
  • Describe in detail any significant changes or findings in the safety profile in the safety update.
  • 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 in the same format as the original submission.
  • Present tabulations of new safety data combined with original application data.
  • Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
  • Provide separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Deficiency summary

The application received a Complete Response due to significant deficiencies primarily related to the comprehensive safety update requirements, including detailed clinical data presentation, worldwide experience summary, and foreign labeling translations. Additionally, issues with proposed prescribing information and proprietary name review termination contributed to the decision.

Findings

Inadequate Prescribing Information

Severity: major

General comments on the proposed package insert, requiring review of labeling resources and related guidance documents prior to resubmission.

Recommended response: Revise the proposed package insert in accordance with FDA's labeling review resources, including regulations and guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.

Proprietary Name Review Terminated

Severity: major

The review of the proposed proprietary name was terminated due to other deficiencies in the application. Resubmission of the name is required only after all other deficiencies are addressed.

Recommended response: Address all other application deficiencies before resubmitting the proposed proprietary name.

Insufficient Safety Update (General)

Severity: critical

Failure to include a comprehensive safety update as described in 21 CFR 314.50(d)(5)(vi)(b), encompassing data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level.

Recommended response: Prepare a complete safety update in accordance with 21 CFR 314.50(d)(5)(vi)(b), integrating all nonclinical and clinical safety data.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Inadequate Clinical Safety Data Presentation

Severity: critical

Deficiencies in presenting new safety data, including: not describing significant changes or findings in the safety profile; failure to incorporate new safety data into sections for discontinuations, serious adverse events, and common adverse events, using the same format as the original submission, combined tabulations, and comparison tables; lack of separate tables for adverse events for indications other than the proposed one; incomplete retabulation of reasons for premature trial discontinuation; missing case report forms and narrative summaries for deaths, adverse event discontinuations, and serious adverse events; lack of information on changes in incidence of common, less serious adverse events; and missing updated exposure information for clinical studies/trials.

Recommended response: Provide detailed clinical safety data, including significant changes, new data integration, comparative tables, retabulated discontinuations, case report forms, narrative summaries, and updated exposure information, following the specified format requirements.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Insufficient Worldwide Safety Experience Summary

Severity: major

Failure to provide a comprehensive summary of worldwide experience on the safety of the product, including an updated estimate of use for product marketed in other countries.

Recommended response: Compile and submit a complete summary of worldwide safety experience, including usage estimates for marketed products.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Missing English Translations of Foreign Labeling

Severity: major

Failure to provide English translations of current approved foreign labeling not previously submitted.

Recommended response: Submit English translations for all current approved foreign labeling not yet provided.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

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 application requires a comprehensive overhaul of its safety data presentation, including detailed clinical trial results, worldwide experience, and foreign labeling, to meet regulatory standards. Labeling and proprietary name issues are secondary but also require resolution.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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