Issued November 13, 2025
Issued
November 13, 2025
Application
Other
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This document is a Complete Response Letter from the FDA to ELC Group regarding New Drug Application (NDA) 205054 for Lutrate®Depot (leuprolide acetate for injection). The FDA has determined that the application cannot be approved in its present form due to deficiencies in clinical/statistical data, product quality, regulatory compliance, prescribing information, proprietary name, facility inspections, and safety update requirements.
The application cannot be approved due to significant deficiencies in demonstrating clinical efficacy (failure to maintain castrate testosterone levels), substantial product quality issues related to formulation, manufacturing controls, drug substance characterization, and stability data, as well as unresolved manufacturing facility inspection findings. Additionally, the scientific justification for reliance on a listed drug under 505(b)(2) was deemed insufficient.
Lutrate Depot 22.5 mg failed to achieve and maintain castrate testosterone levels in an acceptable percentage of patients. The results were difficult to interpret due to marked variations in dose from overfill.
Recommended response: Optimize formulations of Lutrate Depot 22.5 mg and conduct additional clinical trials to demonstrate the safety and efficacy of the products.
The batch formula cannot accurately reflect drug product composition because batches were manufactured with different amounts of excipients.
Recommended response: Provide a batch formula that reflects the proposed composition of the drug product registration batches.
New information about overfill was not provided; only a reference to justifications in the original NDA was made.
Recommended response: Provide justifications (but not calculations) to estimate the amount of reduction in overfill.
Chemical and physical properties of the drug substance must be generated from the actual drug substance batches produced from manufacture.
Recommended response: Provide chemical and physical properties of the drug substance from your manufactured batches.
No stability data for the drug substance were provided. Drug product stability data were only supportive (from annual reports, foreign marketed product, different packaging), thus expiry dating cannot be established.
Recommended response: Provide a stability study and related test data of the three primary batches of the drug substance and drug product.
If relying on FDA's finding of safety and/or effectiveness for one or more listed drugs, scientific appropriateness must be established, as previously discussed in PreNDA meeting minutes.
Recommended response: Establish that such reliance is scientifically appropriate.
Cited: section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act
Comments on the proposed labeling are reserved until the application is otherwise adequate. The applicant is encouraged to review PLR requirements and the SRPI checklist.
Recommended response: Review PLR requirements and the SRPI checklist. If labeling is revised, include updated content of labeling in SPL format.
Cited: 21 CFR 314.50(l)(1)(i)
The proposed proprietary name, Lutrate® Depot, was found acceptable pending approval of the application in the current review cycle.
Recommended response: Resubmit the proposed proprietary name when responding to the application deficiencies.
During a recent inspection of the GP Pharma manufacturing facility, deficiencies were conveyed to the facility representative. Satisfactory resolution of these deficiencies is required before this application may be approved.
Recommended response: Satisfactorily resolve the deficiencies identified during the manufacturing facility inspection.
A comprehensive safety update is required upon responding to the deficiencies, including significant changes in the safety profile, new data from studies, combined data, comparison tables, case report forms for deaths/SAEs, updated exposure, and worldwide experience.
Recommended response: Provide a comprehensive safety update as described in 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The application received a Complete Response due to critical issues in clinical efficacy, specifically the failure to consistently achieve and maintain castrate testosterone levels, compounded by significant product quality deficiencies across formulation, manufacturing, drug substance characterization, and stability data. Unresolved facility inspection findings and insufficient regulatory justification for the 505(b)(2) pathway further contributed to the decision.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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