Issued January 1, 2021
Issued
January 1, 2021
Application
Other • 212122
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This letter from the FDA's Center for Drug Evaluation and Research outlines deficiencies in New Drug Application (NDA) 212122 for Breztri Aerosphere and provides detailed instructions for its resubmission. The deficiencies primarily concern efficacy data, labeling, proprietary name resubmission, and a comprehensive safety update.
The application received a Complete Response Letter primarily due to insufficient clinical data to demonstrate the efficacy of the combination product and the contribution of one of its components. Additionally, a comprehensive safety update is required, along with updated labeling and resubmission of the proprietary name.
Additional clinical trials are required to demonstrate the overall efficacy of the Breztri Aerosphere combination product and specifically the contribution of budesonide to the combination product's effect.
Recommended response: Design and execute new clinical trials to robustly demonstrate efficacy and component contribution, ensuring appropriate statistical power and endpoints.
Updated content of labeling is required in Structured Product Labeling (SPL) format, conforming to 21 CFR 314.50(l)(1)(i). Full review of labeling is reserved until other deficiencies are resolved.
Recommended response: Revise and resubmit the prescribing information in SPL format, ensuring compliance with all relevant regulations and guidance documents, once clinical deficiencies are addressed.
Cited: 21 CFR 314.50(l)(1)(i)
The proposed proprietary name, Breztri Aerosphere, which was previously found acceptable pending approval, must be resubmitted with the complete response to application deficiencies.
Recommended response: Include the proprietary name resubmission as part of the complete response package.
A comprehensive safety update is required, including data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level. This includes: detailed description of significant changes in safety profile; incorporation of new safety data into sections for discontinuations, serious adverse events, and common adverse events (with comparisons to original data); retabulation of premature trial discontinuations; provision of case report forms and narrative summaries for deaths and serious adverse events; description of changes in common, less serious adverse events; updated exposure information; summary of worldwide safety experience; and English translations of current approved foreign labeling.
Recommended response: Compile a thorough safety update addressing all specified points, ensuring data consistency, comprehensive reporting, and compliance with 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The primary theme is the lack of robust clinical evidence for efficacy and component contribution, necessitating further clinical trials. This is compounded by requirements for a comprehensive safety data update and administrative labeling adjustments.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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