Approval Letter Other 210852 (Jan 1, 2024)

Summary

The FDA issued a Complete Response letter for New Drug Application (NDA) 210852 for Cyclophosphamide Injection, indicating that the application cannot be approved in its current form due to deficiencies related to facility inspections and requiring a comprehensive safety update.

Key points

• Satisfactorily resolve objectionable conditions observed during the manufacturing facility inspection.
• 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.
• Incorporate new safety data from studies/clinical trials for the proposed indication, presenting it in the same format as the original submission, with combined tabulations and comparative tables.
• Present separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.
• Retabulate reasons for premature trial discontinuation by incorporating dropouts from newly completed trials and describe any new trends or patterns.
• Provide case report forms and narrative summaries for each subject who died during a clinical trial or who did not complete a trial due to an adverse event, and for serious adverse events.
• Describe any information suggesting a substantial change in the incidence of common, but less serious, adverse events between new data and original application data.

Cited reasons

• Unresolved Manufacturing Facility Deficiencies
• Comprehensive Safety Update Required
• Labeling Review Reserved
• The application received a Complete Response due to unresolved objectionable conditions observed during a manufacturing facility inspection and significant deficiencies in the submitted safety data update. Comments on labeling are reserved until these primary issues are addressed.

Recommended actions

• Satisfactorily resolve objectionable conditions observed during the manufacturing facility inspection.
• 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.
• Incorporate new safety data from studies/clinical trials for the proposed indication, presenting it in the same format as the original submission, with combined tabulations and comparative tables.
• Present separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.
• Retabulate reasons for premature trial discontinuation by incorporating dropouts from newly completed trials and describe any new trends or patterns.
• Provide case report forms and narrative summaries for each subject who died during a clinical trial or who did not complete a trial due to an adverse event, and for serious adverse events.
• Describe any information suggesting a substantial change in the incidence of common, but less serious, adverse events between new data and original application data.

Deficiency summary

The application received a Complete Response due to unresolved objectionable conditions observed during a manufacturing facility inspection and significant deficiencies in the submitted safety data update. Comments on labeling are reserved until these primary issues are addressed.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) of the Federal Food, Drug, and Cosmetic Act

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing facility issues and significant deficiencies in the clinical safety data provided. Labeling review is deferred until these primary concerns are resolved.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%