US FDA•United StatesAL•Approval Letter

Approval Letter Other 212905 (Jan 1, 2024)

Issued January 1, 2024

Issued

January 1, 2024

Application

Other • 212905

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due December 31, 2024Product may be marketed.

Summary

This document is a Complete Response Letter (CRL) from the FDA to Verrica Pharmaceuticals Inc. for New Drug Application (NDA) 212905, indicating that the application for cantharidin topical solution, 7% cannot be approved in its present form. It outlines specific deficiencies and provides detailed instructions for resubmission, focusing on updated labeling, proprietary name resubmission, and a comprehensive safety update.

Key points

Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov, ensuring it conforms with format items in regulations and guidances (e.g., SRPI checklist).
Resubmit the proposed proprietary name (Ycanth) when responding to application deficiencies.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
The safety update must include data from all nonclinical and clinical studies/trials of the drug, regardless of indication, dosage form, or dose level.
Describe in detail any significant changes or findings in the safety profile within the safety update.
When assembling sections for discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data.
Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
Present tabulations of the new safety data combined with the original application data.

Cited reasons

Comprehensive Safety Update Required
Labeling Adequacy Pending
Proprietary Name Resubmission
The application cannot be approved in its current form due to significant deficiencies primarily related to the comprehensive safety update requirements, including detailed data presentation, analysis, and documentation across clinical and nonclinical aspects. Additionally, while the proprietary name was found acceptable, it needs to be resubmitted, and general labeling adequacy is pending resolution of other issues.

Recommended actions

Submit updated content of labeling in Structured Product Labeling (SPL) format as described at FDA.gov, ensuring it conforms with format items in regulations and guidances (e.g., SRPI checklist).
Resubmit the proposed proprietary name (Ycanth) when responding to application deficiencies.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
The safety update must include data from all nonclinical and clinical studies/trials of the drug, regardless of indication, dosage form, or dose level.
Describe in detail any significant changes or findings in the safety profile within the safety update.
When assembling sections for discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data.
Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
Present tabulations of the new safety data combined with the original application data.

Deficiency summary

The application cannot be approved in its current form due to significant deficiencies primarily related to the comprehensive safety update requirements, including detailed data presentation, analysis, and documentation across clinical and nonclinical aspects. Additionally, while the proprietary name was found acceptable, it needs to be resubmitted, and general labeling adequacy is pending resolution of other issues.

Findings

Comprehensive Safety Update Required

Severity: major

A comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This includes: detailed description of significant changes/findings in the safety profile; incorporation of new safety data into sections for discontinuations due to adverse events (AEs), serious AEs, and common AEs with specific formatting (present new data, combine with original, compare frequencies, separate tables for other indications); retabulation of reasons for premature trial discontinuation with newly completed trials' drop-outs and identification of new trends; provision of case report forms and narrative summaries for patients who died or discontinued due to AEs, and for serious AEs; description of information suggesting substantial change in incidence of common, less serious AEs; updated exposure information for clinical studies/trials; summary of worldwide safety experience, including updated estimate of use in other countries; and English translations of current approved foreign labeling not previously submitted.

Recommended response: Conduct a thorough review and analysis of all safety data, ensuring all new and existing data are presented comprehensively, accurately, and in the required format. Provide all requested documentation, including case report forms, narrative summaries, and translations of foreign labeling. Ensure all trends and changes in safety profiles are clearly identified and described.

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

Labeling Adequacy Pending

Severity: major

The FDA reserves comment on the proposed prescribing information, carton, and container labeling until the application is otherwise adequate. The sponsor is encouraged to review labeling resources and use the Selected Requirements for Prescribing Information (SRPI) checklist. Updated content of labeling in Structured Product Labeling (SPL) format is required with the response.

Recommended response: Address all underlying deficiencies first. Once resolved, revise and resubmit all labeling components (prescribing information, carton, container) in SPL format, ensuring full compliance with all relevant regulations and guidances, utilizing the SRPI checklist.

Cited: 21 CFR 314.50(l)(1)(i)

Proprietary Name Resubmission

Severity: minor

The proposed proprietary name, Ycanth, was found acceptable pending approval of the application in the current review cycle. It needs to be resubmitted when responding to the application deficiencies.

Recommended response: Include the proprietary name submission as part of the complete response package, confirming its acceptability and linking it to the overall application approval.

Regulatory context

Submission stage: final decision
Regulatory pathway: NDA

Impact

Impact score: 0.75
Estimated delay: 545 days
Estimated rework cost: $0
Subsequent action: resubmission

Strategic insights

The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, requiring comprehensive data presentation, analysis, and documentation across clinical and nonclinical aspects. Additionally, while the proprietary name was acceptable, it needs resubmission, and general labeling adequacy is pending resolution of other issues.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%

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