Issued June 27, 2024
Issued
June 27, 2024
Application
BLA • 761377
Review center
CBER
Stage
Final Decision
Letter type
Complete Response Letter
This letter from the FDA addresses deficiencies in Biologics License Application (BLA) 761377, requesting specific updates and submissions related to labeling, proprietary name, and a comprehensive safety update. It outlines the requirements for resubmission and the timeline for action.
The application received a Complete Response Letter due to significant deficiencies primarily related to the safety update, requiring comprehensive new data presentation, detailed analyses of safety profile changes, and submission of critical safety documents like case report forms. Additionally, issues with carton and container labeling, proprietary name finalization, and submission of worldwide safety experience and foreign labeling translations were noted.
Submit draft carton and container labeling based on FDA's proposed revisions.
Recommended response: Revise carton and container labeling according to FDA's proposed revisions and resubmit for review.
The proposed proprietary name was found conditionally acceptable pending approval of the application. Resubmit the proposed proprietary name when all application deficiencies are addressed.
Recommended response: Address all other deficiencies and then resubmit the proprietary name for final approval.
A comprehensive safety update is required, including data from all nonclinical and clinical studies of the product, regardless of indication, dosage form, or dose level.
Recommended response: Compile a complete safety update encompassing all relevant nonclinical and clinical data as per FDA requirements.
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 thorough analysis of safety profile changes and clearly articulate their clinical relevance compared to the reference product.
Incorporate new safety data from clinical studies for the proposed indication, presenting it in the same format as the original BLA submission, combined with original BLA data, and include tables comparing frequencies of adverse events.
Recommended response: Reformat and present all new safety data, integrating it with original BLA data and providing comparative frequency tables as requested.
Present a retabulation of reasons for premature study discontinuation, incorporating drop-outs from newly completed studies, and describe any new trends or patterns identified.
Recommended response: Update the analysis of premature study discontinuations, including new data, and identify any emerging trends.
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. Also, provide narrative summaries for serious adverse events.
Recommended response: Collect and submit all required case report forms and narrative summaries for deaths and serious adverse events.
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 BLA data.
Recommended response: Analyze and report any significant changes in the incidence of common adverse events based on new and original BLA data.
Provide updated exposure information for the clinical studies (e.g., number of subjects, person time).
Recommended response: Update and submit comprehensive clinical exposure information for all studies.
Provide a summary of worldwide experience on the safety of this product, including adverse events and immunogenicity, and an updated estimate of use in other countries.
Recommended response: Compile and submit a detailed summary of worldwide safety experience, including immunogenicity and usage estimates.
Provide English translations of current approved foreign labeling not previously submitted.
Recommended response: Obtain and submit English translations for all current approved foreign labeling not yet provided.
The primary themes of the Complete Response Letter are the need for a comprehensive and updated safety profile, including detailed clinical data analysis and documentation, and resolution of labeling-related issues for both carton/container and proprietary name.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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