Complete Response Letter NDA 505b1 215818 (Apr 25, 2025)

Summary

This FDA letter, dated April 25, 2025, addresses New Drug Application (NDA) 215818, outlining specific requirements and recommendations related to product quality, prescribing information, carton and container labeling, and other general submission procedures. It emphasizes the need for the applicant to address deficiencies, update various data points, and adhere to specific formatting and submission guidelines before the application can be approved and the product legally marketed.

Key points

• The applicant must review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• The applicant must use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• The applicant's response must include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• The applicant must describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.
• The applicant must provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
• The applicant must provide a summary of worldwide experience on the safety of this drug, including an updated estimate of use for drug marketed in other countries.
• The applicant must provide English translations of current approved foreign labeling not previously submitted.
• The applicant is required to resubmit or take other actions available under 21 CFR 314.110 within one year after the date of this letter.

Cited reasons

• Insufficient Clinical Exposure Information
• Inadequate Worldwide Safety Summary
• Missing English Translations of Foreign Labeling
• The application is not approvable due to outstanding issues related to insufficient clinical exposure data, a lack of comprehensive worldwide safety experience, and missing English translations of foreign labeling. The agency reserves comment on proposed labeling until other deficiencies are addressed.

Recommended actions

• The applicant must review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• The applicant must use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• The applicant's response must include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• The applicant must describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.
• The applicant must provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
• The applicant must provide a summary of worldwide experience on the safety of this drug, including an updated estimate of use for drug marketed in other countries.
• The applicant must provide English translations of current approved foreign labeling not previously submitted.
• The applicant is required to resubmit or take other actions available under 21 CFR 314.110 within one year after the date of this letter.

Deficiency summary

The application is not approvable due to outstanding issues related to insufficient clinical exposure data, a lack of comprehensive worldwide safety experience, and missing English translations of foreign labeling. The agency reserves comment on proposed labeling until other deficiencies are addressed.

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 revolve around insufficient clinical data to fully assess safety and exposure, and administrative gaps in global product information, particularly regarding foreign labeling. Resolution of these issues is required before labeling can be finalized.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%