Issued April 19, 2024
Issued
April 19, 2024
Application
BLA • 761187
Review center
CBER
Stage
Final Decision
Letter type
Complete Response Letter
This FDA letter, pertaining to Biologics License Application (BLA) 761187, outlines deficiencies and requirements for the applicant to address. It covers aspects of prescription drug labeling, carton and container labeling, proprietary name resubmission, and a comprehensive safety update. The letter also provides instructions for resubmission and notes that the product cannot be marketed until approved.
The application received a Complete Response Letter due to significant deficiencies primarily related to incomplete safety data reporting and analysis, as well as unresolved labeling issues. Key issues include missing case report forms and narrative summaries for adverse events, inadequate exposure information, an incomplete summary of worldwide safety experience, and outstanding carton/container labeling and proprietary name resubmission requirements.
The applicant failed to submit draft carton and container labeling based on the agency's proposed revisions.
Recommended response: Revise and resubmit carton and container labeling in accordance with the FDA's proposed revisions.
The proposed proprietary name was found conditionally acceptable but requires resubmission once all other application deficiencies identified in this letter have been addressed.
Recommended response: Resubmit the proposed proprietary name after all other deficiencies in the Complete Response Letter have been fully resolved.
The safety update provided was inadequate, lacking detailed descriptions of significant changes or findings in the safety profile from all nonclinical and clinical studies, and their relevance to potential clinically meaningful differences between the proposed biosimilar and the U.S.-licensed reference product.
Recommended response: Provide a comprehensive safety update detailing all significant changes or findings from nonclinical and clinical studies, and analyze their relevance to biosimilarity.
The applicant failed to provide case report forms and narrative summaries for subjects who died during a clinical study or who did not complete a study due to an adverse event. Additionally, narrative summaries for serious adverse events were not provided.
Recommended response: Submit all missing case report forms and narrative summaries for deaths, study discontinuations due to adverse events, and all serious adverse events.
The submission lacked updated exposure information for the clinical studies, including details such as the number of subjects and person-time.
Recommended response: Provide complete and updated exposure information for all clinical studies, including subject counts and person-time data.
The applicant did not provide a comprehensive summary of worldwide experience regarding the product's safety, including known adverse events, immunogenicity data, and an updated estimate of product use in other countries.
Recommended response: Compile and submit a thorough summary of worldwide safety experience, including adverse events, immunogenicity, and updated global usage estimates.
English translations of current approved foreign labeling that had not been previously submitted were not provided.
Recommended response: Submit English translations for all current approved foreign labeling that has not yet been included in the application.
The primary themes of the Complete Response are significant deficiencies in clinical safety data reporting and analysis, particularly regarding adverse events, exposure, and global experience, coupled with outstanding issues in product labeling and administrative requirements.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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