Issued November 13, 2025
Issued
November 13, 2025
Application
Other
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response Letter from the FDA to Citius Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) for Lymphir (denileukin diftitox-cxdl) for injection. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations that must be addressed.
The application for Lymphir received a Complete Response due to significant deficiencies in product quality (details redacted), an uncompleted manufacturing facility inspection, inadequate prescribing information requiring format and content updates, and the need for a comprehensive safety update.
Specific product quality deficiencies were identified, but details are withheld as confidential commercial information (b4 (CCI/TS)). These issues prevent approval in the current form.
Recommended response: Address all specific product quality deficiencies as detailed in the withheld sections of the letter. This likely involves further data submission, process improvements, or analytical method validation to ensure product quality and consistency.
An inspection of a manufacturing facility (FEI #) is required before this application can be approved. Due to the timing of incorporation of the site into the license application, the FDA was unable to conduct an inspection during the current review cycle.
Recommended response: Coordinate immediately with the FDA to schedule and successfully complete the required facility inspection. Ensure the facility is fully prepared and compliant with current Good Manufacturing Practices (CGMP).
Submit draft labeling responsive to the electronic communication dated July 14, 2023. Correct formatting errors using the SRPI checklist and submit updated content of labeling in structured product labeling (SPL) format as described at FDA.gov, conforming to 21 CFR 601.14(b). The proposed Prescribing Information (PI) must also conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
Recommended response: Revise the Prescribing Information (PI) and submit in SPL format, ensuring full compliance with all cited regulations and guidance documents. Utilize the SRPI checklist for formatting and provide both marked-up and clean Word versions to facilitate review.
Cited: 21 CFR 601.14(b), 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57
Include a comprehensive safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies. This update must detail significant changes in the safety profile, present new safety data from studies/trials, provide retabulations of adverse events, include case report forms and narrative summaries for deaths or discontinuations due to adverse events, and provide updated exposure information.
Recommended response: Compile and submit a comprehensive safety update, including all requested data and analyses, ensuring full compliance with 21 CFR 314.50(d)(5)(vi)(b) and addressing all specific data presentation requirements for clinical and nonclinical safety information.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The proposed proprietary name, Lymphir, was found acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.
Recommended response: Include the previously accepted proprietary name in the resubmission package as part of the administrative updates.
The BLA for Lymphir received a Complete Response due to critical manufacturing site inspection issues, undisclosed product quality concerns, and deficiencies in labeling content/format and the required safety update. These issues collectively prevent approval and necessitate a comprehensive resubmission.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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