Issued October 29, 2024
Issued
October 29, 2024
Application
BLA • 761147
Review center
CBER
Stage
Final Decision
Letter type
Complete Response Letter
This document is a deficiency letter from the FDA regarding Biologics License Application (BLA) 761147. It addresses proposed labeling, proprietary name, and outlines detailed requirements for a safety update, including specific data presentation and analysis. It also provides instructions for resubmission and potential consequences of inaction.
The application is not ready for approval due to significant deficiencies primarily related to clinical safety data, including the need for comprehensive safety updates, detailed adverse event reporting, updated exposure information, and a summary of worldwide safety experience. Additionally, the proprietary name requires resubmission, and English translations of foreign labeling are needed.
The proprietary name was found conditionally acceptable but must be resubmitted when all other application deficiencies are addressed.
Recommended response: Resubmit the proposed proprietary name concurrently with the complete response addressing all other deficiencies.
Provide a comprehensive safety update including data from all nonclinical and clinical studies of the product, regardless of indication, dosage form, or dose level.
Recommended response: Compile and submit a thorough safety update encompassing all relevant nonclinical and clinical data.
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.
Recommended response: Perform a detailed analysis of any significant changes in the safety profile and clearly articulate their clinical relevance.
Incorporate new safety data from clinical studies into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events. This includes presenting new data in the original BLA format, tabulating new data combined with original BLA data, and comparing frequencies of adverse events.
Recommended response: Re-tabulate and present all safety data (new and original) in a consistent format, including comparative tables for adverse event frequencies.
Present a retabulation of the reasons for premature study discontinuation by incorporating dropouts from newly completed studies and describe any new trends or patterns identified.
Recommended response: Update and analyze premature study discontinuation data, identifying and describing any new trends or patterns.
Provide case report forms and narrative summaries for each subject who died during a clinical study or did not complete a study due to an adverse event. Additionally, provide narrative summaries for all serious adverse events.
Recommended response: Compile and submit all requested case report forms and narrative summaries for deaths and serious adverse events to ensure data completeness and transparency.
Provide updated exposure information for the clinical studies, including metrics such as the number of subjects and person-time.
Recommended response: Update and submit comprehensive clinical study exposure data.
Provide a summary of worldwide experience on the safety of this product, including adverse events known to be associated with its use and immunogenicity. Include an updated estimate of use for this product marketed in other countries.
Recommended response: Compile and submit a comprehensive summary of worldwide safety experience, including immunogenicity data and global usage estimates.
Provide English translations of current approved foreign labeling that has not been previously submitted.
Recommended response: Provide English translations for all relevant and currently approved foreign labeling documents.
The primary theme of the Complete Response Letter is the inadequacy of clinical safety data and its presentation, requiring a comprehensive update and detailed analysis of adverse events, exposure, and worldwide experience. Secondary themes include administrative requirements for proprietary name resubmission and foreign labeling translations.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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