Issued January 1, 2019
Issued
January 1, 2019
Application
Other • 761073
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response letter from the FDA to Amgen Inc. regarding their Biologics License Application (BLA) for Kanjinti (ABP 980). The FDA has determined that the application cannot be approved in its present form due to several deficiencies, including unresolved facility inspection issues, pending labeling revisions, and requirements for a comprehensive safety update and additional manufacturing/testing data.
The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, outstanding issues with carton and container labeling, the need to resubmit the proprietary name, and significant requirements for a comprehensive safety update including clinical data, worldwide experience, and immunogenicity. Additionally, several CMC-related comments regarding testing, characterization, validation, and manufacturing process modifications need to be addressed.
Satisfactory resolution of deficiencies identified during a recent inspection of the manufacturing facility is required before this application may be approved.
Recommended response: Address all deficiencies identified during the facility inspection and provide evidence of satisfactory resolution to the agency.
Submit draft carton and container labeling based on the FDA's proposed revisions dated March 6, 2018. The response must include updated content of labeling in structured product labeling (SPL) format.
Recommended response: Revise and resubmit carton and container labeling according to FDA's proposed revisions, ensuring compliance with SPL format requirements.
Cited: 21 CFR 601.14(b)
The proposed proprietary name, Kanjinti, was found acceptable pending approval of the application. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name along with the complete response to all other deficiencies.
A detailed safety update is required, including: significant changes/findings in the safety profile, incorporation of new clinical safety data (tabulations, comparisons), retabulation of reasons for premature study discontinuation, case report forms and narrative summaries for patient deaths or adverse event-related discontinuations, narrative summaries for serious adverse events, information on changes in common adverse event incidence, updated clinical exposure information, a summary of worldwide safety experience (including adverse events and immunogenicity), and English translations of current approved foreign labeling.
Recommended response: Conduct a thorough safety update, compile all requested data (CRFs, narratives, tabulations, worldwide experience), and provide detailed analyses as specified by the agency.
Several CMC-related issues need to be addressed: 1. Implement an Fc γRIIIa binding test on drug substance release specification and propose an acceptance criterion. 2. Conduct additional characterization to understand the impact of drug product manufacturing and stability on Fc functions, and update the overall control strategy. 3. Provide sterilization validation information for specific components in section 3.2.P.3.5. 4. Perform media fill simulations that include specific components and submit the data in section 3.2.P.3.5. 5. Provide validation data for specific components in section 3.2.P.3.5. 6. Implement necessary equipment modifications to designate specific components in the manufacturing process.
Recommended response: Address each CMC comment by implementing required tests, conducting characterization, performing validations, and making necessary equipment modifications, then submit the updated data and proposals in the appropriate modules.
The application requires substantial additional data and resolution of manufacturing quality issues, comprehensive clinical safety updates, and labeling revisions to meet regulatory approval standards, indicating a need for significant data generation, process improvements, and documentation updates across multiple domains.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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