Approval Letter Other 761279 (Jan 1, 2023)

Summary

This is a Complete Response Letter from the FDA to Eli Lilly and Company regarding their Biologics License Application (BLA) 761279 for LY3074828 injection for ulcerative colitis. The FDA has determined that the application cannot be approved in its current form due to deficiencies related to facility inspections, prescribing information, and the need for a comprehensive safety update.

Key points

• Achieve satisfactory resolution of deficiencies identified during the pre-license inspection of the ELI LILLY AND COMPANY manufacturing facility in Indianapolis, Indiana (FEI 1819470).
• Submit draft labeling that is responsive to electronic communications dated March 15, 2023 (for Prescribing Information and Medication Guide) and March 2, 2023 (for Instructions for Use).
• 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.
• Resubmit the proposed proprietary name when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Describe in detail any significant changes or findings in the safety profile within the safety update.
• Incorporate new safety data from studies/clinical trials for the proposed indication into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, using the same format as the original submission.

Cited reasons

• Unresolved Manufacturing Facility Inspection Deficiencies
• Inadequate Prescribing Information and Formatting
• Proprietary Name Resubmission Required
• Incomplete Safety Update
• The application cannot be approved in its present form due to unresolved manufacturing facility inspection deficiencies, inadequate prescribing information and formatting, and an incomplete safety update requiring significant additional data and analysis.

Recommended actions

• Achieve satisfactory resolution of deficiencies identified during the pre-license inspection of the ELI LILLY AND COMPANY manufacturing facility in Indianapolis, Indiana (FEI 1819470).
• Submit draft labeling that is responsive to electronic communications dated March 15, 2023 (for Prescribing Information and Medication Guide) and March 2, 2023 (for Instructions for Use).
• 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.
• Resubmit the proposed proprietary name when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Describe in detail any significant changes or findings in the safety profile within the safety update.
• Incorporate new safety data from studies/clinical trials for the proposed indication into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, using the same format as the original submission.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility inspection deficiencies, inadequate prescribing information and formatting, and an incomplete safety update requiring significant additional data and analysis.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA 351(a)

Impact

Impact score

0.95

Estimated delay

270 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing site deficiencies, non-compliant labeling, and insufficient safety data updates, necessitating a comprehensive resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%