Approval Letter Other 206976 (Jan 1, 2018)

Summary

This document is an 'Other Action Letter' from the FDA regarding New Drug Application (NDA) 206976, outlining deficiencies that need to be addressed before the application can be approved. It details specific requirements related to biopharmaceutics, quality control, labeling, proprietary name, and safety updates.

Key points

• Address the inadequacy of the weight-of-evidence approach for the manufacturing site change by providing in vivo data or conducting an adequate and well-controlled clinical efficacy and safety study to bridge products from different manufacturing sites.
• Provide additional data demonstrating the discriminating ability of the method towards meaningful changes of critical material attributes or process parameters to support its adequacy as a QC tool for drug product release and stability testing.
• Review labeling resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Ensure that the prescribing information conforms with format items in regulations and guidances using the SRPI checklist if labeling is revised.
• Include updated content of labeling in structured product labeling (SPL) format in the response.
• Resubmit the proposed proprietary name, 'Licart', when responding to the 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 describe any significant changes or findings in the safety profile.

Cited reasons

• Inadequate Biopharmaceutics data for manufacturing site change
• Insufficient discriminating ability of analytical method
• Labeling content and format updates required
• Proprietary name resubmission required
• Comprehensive safety update required
• The application received a Complete Response Letter due to inadequate biopharmaceutics data for a manufacturing site change, insufficient discriminating ability of an analytical method, and extensive requirements for a comprehensive safety update. Labeling updates in SPL format and resubmission of the proprietary name are also required.

Recommended actions

• Address the inadequacy of the weight-of-evidence approach for the manufacturing site change by providing in vivo data or conducting an adequate and well-controlled clinical efficacy and safety study to bridge products from different manufacturing sites.
• Provide additional data demonstrating the discriminating ability of the method towards meaningful changes of critical material attributes or process parameters to support its adequacy as a QC tool for drug product release and stability testing.
• Review labeling resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Ensure that the prescribing information conforms with format items in regulations and guidances using the SRPI checklist if labeling is revised.
• Include updated content of labeling in structured product labeling (SPL) format in the response.
• Resubmit the proposed proprietary name, 'Licart', when responding to the 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 describe any significant changes or findings in the safety profile.

Deficiency summary

The application received a Complete Response Letter due to inadequate biopharmaceutics data for a manufacturing site change, insufficient discriminating ability of an analytical method, and extensive requirements for a comprehensive safety update. Labeling updates in SPL format and resubmission of the proprietary name are also required.

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 are significant data gaps related to manufacturing site change bridging and analytical method validation, coupled with extensive requirements for a comprehensive safety data update to support the application.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%