Issued January 1, 2022
Issued
January 1, 2022
Application
Other • 761180
Review center
Other
Stage
Late Cycle
Letter type
Approval Letter
This letter from the FDA's Center for Drug Evaluation and Research addresses deficiencies in Biologics License Application (BLA) 761180, specifically requesting a resubmission of the proposed proprietary name and a comprehensive safety update.
The agency requires a comprehensive safety update, including detailed patient-level data for serious adverse events and deaths, revised safety data presentations, and an analysis of common adverse event incidence. Additionally, the proposed proprietary name needs to be resubmitted.
Resubmit the proposed proprietary name when responding to application deficiencies. The name was previously found acceptable pending approval of the application in the current review cycle.
Recommended response: Ensure the proprietary name submission package is complete and aligns with previous agreements, confirming no new issues have arisen since the prior acceptance.
Provide a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). This update should include data from all nonclinical and clinical studies/trials of the drug under consideration, regardless of indication, dosage form, or dose level. Describe in detail any significant changes or findings in the safety profile.
Recommended response: Compile all relevant safety data from both nonclinical and clinical studies, ensuring comprehensive coverage across all indications and dose levels. Clearly articulate any new or significant safety findings.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events. Present new safety data from studies/clinical trials for the proposed indication using the same format as the original submission. Present tabulations of the new safety data combined with the original application data. Include tables comparing frequencies of adverse events in the original application with the retabulated frequencies. For indications other than the proposed indication, provide separate tables for adverse event frequencies.
Recommended response: Re-analyze and re-present all safety data according to the specified formats, ensuring clear comparisons between original and new data, and separate presentations for different indications. Focus on consistency with the original submission format where applicable.
Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for all serious adverse events.
Recommended response: Expedite the collection and submission of all requested case report forms and detailed narrative summaries for critical safety events, ensuring accuracy and completeness for each patient.
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 application data.
Recommended response: Perform a thorough comparative analysis of common adverse event incidence, highlighting any significant shifts or trends between the original and new datasets.
The primary theme is the critical need for a comprehensive and meticulously organized update of all safety data, including detailed patient-level information for serious events, and a re-submission of the proprietary name to address significant deficiencies before approval can be considered.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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