Issued November 13, 2025
Issued
November 13, 2025
Application
Other
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This letter from the FDA outlines deficiencies in a Biologics License Application (BLA 761367) and provides specific requirements for resubmission. It covers various aspects including filling capability data, prescribing information, proprietary name, safety updates, microbiology, product quality, and device performance, emphasizing the need for comprehensive data and adherence to regulatory standards for approval.
The application received a Complete Response Letter due to significant deficiencies across Chemistry, Manufacturing, and Controls (CMC), Clinical Safety, and Labeling. Key issues include insufficient filling capability data, missing real-time shipping validation, incomplete device performance stability data, inadequate safety update presentation, and non-compliant prescribing information.
Provide filling capability data derived from sufficient samples and multiple sampling points of PPQ batches to demonstrate that the filling process is capable of filling syringes with consistent filling weight/volume.
Recommended response: Conduct additional filling capability studies with sufficient samples and sampling points from PPQ batches to demonstrate process consistency.
Submit draft labeling responsive to FDA's electronic communication dated October 4, 2024. Correct formatting errors using the SRPI checklist. Submit updated content of labeling [21 CFR 601.14(b)] in structured product labeling (SPL) format. Provide a highlighted/marked-up copy showing all changes, as well as a clean Word version.
Recommended response: Revise PI according to FDA's electronic communication, SRPI checklist, and relevant regulations. Ensure SPL format and provide both marked-up and clean versions for review.
Cited: 21 CFR 601.14(b), 21 CFR 201.56(a), 21 CFR 201.56(d), 201.57
The proposed proprietary name 'Andembry' was found conditionally acceptable. Resubmit the proposed proprietary name only after all application deficiencies identified in this letter have been addressed.
Recommended response: Do not resubmit the proprietary name until all other deficiencies outlined in the Complete Response Letter are fully resolved and submitted.
Include a comprehensive safety update with data from all nonclinical and clinical studies/trials. Detail significant changes, present new safety data in the original format, combine with original data, compare frequencies, provide separate tables for other indications, retabulate reasons for premature discontinuation, provide case report forms/narrative summaries for deaths/SAEs, describe changes in common AEs, update exposure information, summarize worldwide experience, and provide English translations of foreign labeling.
Recommended response: Compile a thorough safety update addressing all specified data points, including detailed analyses, comparisons, and narrative summaries for critical events, ensuring all required information is presented clearly and comprehensively.
The plunger movement study described in section 3.2.P.2.5 was not conducted under worst-case conditions (largest air bubble allowed). Provide results from a repeated plunger movement study conducted with syringes with the largest allowed air bubble to ensure sterility of the drug product during routine transport.
Recommended response: Repeat the plunger movement study under worst-case conditions, specifically with the largest allowed air bubble, and submit the results to demonstrate sterility assurance during transport.
Real-time/real-condition drug product shipping validation data was not provided. Submitting this data in an annual report without an approved shipping validation protocol for prospective validation is inappropriate. Provide this data in the resubmission.
Recommended response: Conduct and submit real-time/real-condition shipping validation data with an approved protocol as part of the resubmission to ensure product quality during shipment.
FDA requested device performance testing (real-time or accelerated aged) on 3 batches of prefilled syringe (PFS) with needle safety device (NSD) and autoinjector (AI) to demonstrate performance over a 36-month shelf life. Additional stability data was promised for an annual report; however, it must be provided in the resubmission.
Recommended response: Provide the results of the additional stability data for the PFS with NSD and AI in the resubmission, rather than deferring to an annual report, to support device performance claims.
The application faces significant hurdles to approval due to critical gaps in CMC data, particularly regarding manufacturing process validation, shipping validation, and device performance stability. Additionally, the clinical safety data presentation is deemed insufficient, and the proposed labeling requires substantial revisions to meet regulatory compliance and formatting standards.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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