Approval Letter Other 761127 (Jan 1, 2022)

Summary

This is a Complete Response Letter from the FDA to Revance Therapeutics, Inc. regarding their Biologics License Application (BLA) 761127 for daxibotulinumtoxinA for injection. The FDA has determined that the application cannot be approved in its present form due to unresolved manufacturing facility deficiencies and pending labeling issues. The letter outlines the required actions for resubmission, including resolving manufacturing issues, revising prescribing information and carton/container labeling, resubmitting the proprietary name, and providing a comprehensive safety update.

Key points

• Satisfactory resolution of deficiencies identified during the inspection of the REVANCE THERAPEUTICS, INC manufacturing facility (FEI 3007772056) is required.
• 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 that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 601.14(b)] in structured product labeling (SPL) format in the response.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name, Daxxify, 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 in detail any significant changes or findings in the safety profile.

Cited reasons

• Unresolved Manufacturing Facility Deficiencies
• Missing Medication Guide Statement on Carton and Container Labeling
• Resubmit Proprietary Name with Response
• Comprehensive Safety Update Required
• The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, outstanding issues related to carton and container labeling, and the need for a comprehensive safety update with specific data requirements. The proprietary name, Daxxify, was found acceptable but requires resubmission with the response.

Recommended actions

• Satisfactory resolution of deficiencies identified during the inspection of the REVANCE THERAPEUTICS, INC manufacturing facility (FEI 3007772056) is required.
• 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 that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 601.14(b)] in structured product labeling (SPL) format in the response.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name, Daxxify, 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 in detail any significant changes or findings in the safety profile.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, outstanding issues related to carton and container labeling, and the need for a comprehensive safety update with specific data requirements. The proprietary name, Daxxify, was found acceptable but requires resubmission with the response.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

270 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary hurdle for approval is unresolved manufacturing quality system deficiencies. Additionally, the submission requires specific labeling updates and a thorough, data-intensive safety update covering clinical, nonclinical, and global experience.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%