FDA CRL - ELC Group

The FDA issued a Complete Response Letter (CRL) to ELC Group, agent for GP Pharm, S.A., regarding their New Drug Application (NDA 205054) for Lutrate® Depot (leuprolide acetate for injection), 22.5 mg/vial, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application cannot be approved in its current form due to several deficiencies.

Key issues include clinical and product quality concerns. Clinically, Lutrate Depot failed to consistently achieve and maintain castrate testosterone levels, a surrogate marker for efficacy in advanced prostate cancer, with efficacy results potentially impacted by dose variations from vial overfill. The FDA requires formulation optimization and additional clinical trials to demonstrate safety and efficacy.

From a product quality standpoint, the batch formula was inaccurate due to inconsistent excipient amounts, and insufficient justification for overfill was provided. The applicant also lacked chemical/physical properties from actual manufactured drug substance batches and adequate stability data for both drug substance and drug product, preventing expiry dating.

Furthermore, a recent inspection of GP Pharm's manufacturing facility identified deficiencies that require satisfactory resolution. The application also lacked scientific justification for relying on FDA's previous safety and effectiveness findings for listed drugs. GP Pharm must address these manufacturing issues, provide revised batch formulas, new overfill justifications, drug substance properties, and comprehensive stability studies. A safety update and updated prescribing information are also required.