Approval Letter Other 761275 (Jan 1, 2024)

Summary

This is a Complete Response Letter from the FDA to Fresenius Kabi USA, LLC, for their Biologics License Application (BLA) 761275 for MSB11456. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facilities, and requires a comprehensive safety update and other technical revisions before approval.

Key points

• Satisfactorily resolve deficiencies identified during inspections of Fresenius Kabi Austria GmbH and other listed facilities.
• Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the FDA guidance for industry Labeling for Biosimilar Products.
• Resubmit the proposed proprietary name (Tyenne) when responding to application deficiencies.
• Include a safety update with the response to deficiencies, encompassing data from all nonclinical and clinical studies of the product.
• Describe in detail any significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.
• Present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.
• Present tabulations of new safety data combined with original BLA data.
• Include tables comparing frequencies of adverse events in the original BLA with retabulated frequencies.

Cited reasons

• Unsatisfactory Resolution of Manufacturing Facility Deficiencies
• Comprehensive Clinical Safety Update Required
• Resubmission of Proprietary Name
• English Translations of Foreign Labeling
• The application cannot be approved due to unresolved manufacturing facility deficiencies, incomplete clinical safety data requiring a comprehensive update, and administrative issues related to proprietary name resubmission and foreign labeling translations.

Recommended actions

• Satisfactorily resolve deficiencies identified during inspections of Fresenius Kabi Austria GmbH and other listed facilities.
• Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the FDA guidance for industry Labeling for Biosimilar Products.
• Resubmit the proposed proprietary name (Tyenne) when responding to application deficiencies.
• Include a safety update with the response to deficiencies, encompassing data from all nonclinical and clinical studies of the product.
• Describe in detail any significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.
• Present new safety data from clinical studies for the proposed indication using the same format as the original BLA submission.
• Present tabulations of new safety data combined with original BLA data.
• Include tables comparing frequencies of adverse events in the original BLA with retabulated frequencies.

Deficiency summary

The application cannot be approved due to unresolved manufacturing facility deficiencies, incomplete clinical safety data requiring a comprehensive update, and administrative issues related to proprietary name resubmission and foreign labeling translations.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

section 351(k) of the Public Health Service Act

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The complete response is primarily driven by unresolved manufacturing facility issues, a need for a comprehensive update to clinical safety data, and administrative requirements for proprietary name resubmission and foreign labeling translations.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%