Approval Letter Other (Nov 13, 2025)

Summary

This is a Complete Response letter from the FDA to Cadence Pharmaceuticals regarding their New Drug Application (NDA) for Ofirmev (acetaminophen) Injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, labeling, and the need for a comprehensive safety update.

Key points

• Satisfactory compliance with Current Good Manufacturing Practices (CGMP) for Drugs is required for all manufacturing and testing facilities listed in the NDA.
• If labeling is revised, the response must include updated content of labeling in Structured Product Labeling (SPL) format.
• 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.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as the original NDA submission.
• Present tabulations of new safety data combined with original NDA data.
• Include tables that compare frequencies of adverse events in the original NDA with retabulated frequencies.
• For indications other than the proposed indication, provide separate tables for frequencies of adverse events occurring in clinical trials.

Cited reasons

• Manufacturing Facility Inspection Deficiencies
• Inadequate Safety Update Submission
• Labeling Comments Reserved
• The application cannot be approved in its current form due to unresolved manufacturing facility inspection deficiencies and a requirement for a comprehensive safety update. The safety update needs to include new clinical data, retabulations, case report forms, worldwide experience, and translated foreign labeling. Labeling comments are reserved until these primary issues are addressed.

Recommended actions

• Satisfactory compliance with Current Good Manufacturing Practices (CGMP) for Drugs is required for all manufacturing and testing facilities listed in the NDA.
• If labeling is revised, the response must include updated content of labeling in Structured Product Labeling (SPL) format.
• 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.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as the original NDA submission.
• Present tabulations of new safety data combined with original NDA data.
• Include tables that compare frequencies of adverse events in the original NDA with retabulated frequencies.
• For indications other than the proposed indication, provide separate tables for frequencies of adverse events occurring in clinical trials.

Deficiency summary

The application cannot be approved in its current form due to unresolved manufacturing facility inspection deficiencies and a requirement for a comprehensive safety update. The safety update needs to include new clinical data, retabulations, case report forms, worldwide experience, and translated foreign labeling. Labeling comments are reserved until these primary issues are addressed.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2)

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing quality issues at a third-party facility and significant deficiencies in the submitted safety update, requiring extensive additional clinical and nonclinical data, as well as global safety information.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%