Complete Response Letter NDA 505b1 218408 (Mar 27, 2024)

Summary

This FDA letter addresses deficiencies in New Drug Application (NDA) 218408, specifically regarding prescribing information, carton and container labeling, and safety updates. It outlines requirements for resubmission and emphasizes that the product cannot be marketed until approved.

Key points

• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• 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 product under consideration regardless of indication, dosage form, or dose level.
• 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 using the same format as in the original submission when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
• Resubmit the application or take other actions available under 21 CFR 314.110 within one year after the date of this letter.

Cited reasons

• Inadequate Prescribing Information
• Inadequate Carton and Container Labeling
• Requirement for Safety Update
• The application received a Complete Response due to deficiencies primarily related to inadequate prescribing information and carton/container labeling, and the requirement for a comprehensive safety update. The prescribing information needs to be updated and submitted in Structured Product Labeling (SPL) format, and a safety update incorporating all new nonclinical and clinical data is mandatory for resubmission.

Recommended actions

• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• 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 product under consideration regardless of indication, dosage form, or dose level.
• 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 using the same format as in the original submission when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
• Resubmit the application or take other actions available under 21 CFR 314.110 within one year after the date of this letter.

Deficiency summary

The application received a Complete Response due to deficiencies primarily related to inadequate prescribing information and carton/container labeling, and the requirement for a comprehensive safety update. The prescribing information needs to be updated and submitted in Structured Product Labeling (SPL) format, and a safety update incorporating all new nonclinical and clinical data is mandatory for resubmission.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes for the Complete Response are deficiencies in product labeling (prescribing information, carton, and container) and the necessity for a comprehensive safety update encompassing all nonclinical and clinical data.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%