Assyro AI
US FDA•United StatesCRL•Complete Response Letter

Complete Response Letter NDA 505b1 218600 (Oct 21, 2024)

Issued October 21, 2024

Issued

October 21, 2024

Application

NDA 505b1 • 218600

Review center

CDER

Stage

Final Decision

Letter type

Complete Response Letter

Response due October 21, 2025Requires resubmission addressing deficiencies.

Summary

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218600. It outlines deficiencies and provides detailed instructions for resubmitting the application, focusing on labeling, proprietary name, and safety updates.

Key points

  • Submit draft labeling responsive to the FDA's electronic communication.
  • Include the labeling response in the application resubmission.
  • Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
  • Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov, in accordance with 21 CFR 314.50(l)(1)(i).
  • Provide a highlighted or marked-up copy showing all changes to the labeling, along with a clean Word version.
  • Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
  • Submit draft carton and container labeling based on the FDA's proposed revisions.
  • Include the response regarding carton and container labeling in the resubmission.

Cited reasons

  • Incomplete Prescribing Information (PI) and Formatting Errors
  • Incomplete Carton and Container Labeling
  • Proprietary Name Resubmission Required
  • Inadequate Safety Update
  • The FDA issued a Complete Response Letter primarily due to significant deficiencies in the proposed prescribing information, carton and container labeling, and the need for a comprehensive safety update. The proprietary name was conditionally acceptable but requires resubmission after all other deficiencies are addressed. The submission failed to meet content and formatting regulations for labeling and lacked a complete safety profile update.

Recommended actions

  • Submit draft labeling responsive to the FDA's electronic communication.
  • Include the labeling response in the application resubmission.
  • Use the SRPI checklist to correct any formatting errors in the labeling to ensure conformance with regulations and guidances.
  • Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov, in accordance with 21 CFR 314.50(l)(1)(i).
  • Provide a highlighted or marked-up copy showing all changes to the labeling, along with a clean Word version.
  • Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
  • Submit draft carton and container labeling based on the FDA's proposed revisions.
  • Include the response regarding carton and container labeling in the resubmission.

Deficiency summary

The FDA issued a Complete Response Letter primarily due to significant deficiencies in the proposed prescribing information, carton and container labeling, and the need for a comprehensive safety update. The proprietary name was conditionally acceptable but requires resubmission after all other deficiencies are addressed. The submission failed to meet content and formatting regulations for labeling and lacked a complete safety profile update.

Findings

Incomplete Prescribing Information (PI) and Formatting Errors

Severity: major

The draft Prescribing Information (PI) was not responsive to prior electronic communications and contained formatting errors. It did not conform to the content and format regulations specified in 21 CFR 201.56(a), (d), and 201.57. An updated content of labeling in Structured Product Labeling (SPL) format is required.

Recommended response: Revise draft Prescribing Information to address all agency comments, ensure compliance with 21 CFR 201.56(a), (d), 201.57, and 314.50(l)(1)(i), and submit in SPL format. Utilize the SRPI checklist for formatting.

Cited: 21 CFR 314.50(l)(1)(i), 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57

Incomplete Carton and Container Labeling

Severity: major

The draft carton and container labeling was not based on the agency's proposed revisions. A revised version incorporating these revisions is required.

Recommended response: Submit revised draft carton and container labeling incorporating agency's proposed revisions.

Proprietary Name Resubmission Required

Severity: minor

The proposed proprietary name was found conditionally acceptable pending approval of the application. It must be resubmitted once all other application deficiencies identified in this letter have been addressed.

Recommended response: Resubmit the proposed proprietary name once all other application deficiencies are fully addressed.

Inadequate Safety Update

Severity: major

A comprehensive safety update is required as described in 21 CFR 314.50(d)(5)(vi)(b). This includes new safety data from all nonclinical and clinical studies, combined tabulations with original data, comparison tables, separate tables for other indications, retabulation of premature discontinuations, case reports for deaths/SAEs, analysis of changes in common AEs, updated exposure information, worldwide experience, and English translations of current approved foreign labeling.

Recommended response: Provide a complete safety update as per 21 CFR 314.50(d)(5)(vi)(b), incorporating all new safety data, detailed analyses, and worldwide experience.

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

Regulatory context

Submission stage
final decision
Regulatory pathway
NDA

Impact

Impact score
0.75
Estimated delay
270 days
Estimated rework cost
$0
Subsequent action
resubmission

Strategic insights

The primary themes of the Complete Response Letter are significant deficiencies in labeling content and format across prescribing information, carton, and container labeling, and the requirement for a comprehensive and updated safety profile analysis.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%

Document viewer

Read the FDA letter and send context to the co-pilot at any time.

Loading document viewer…