FDA CRL - Therakind Limited

The FDA issued a Complete Response Letter (CRL) to Therakind Limited regarding their New Drug Application (NDA 212479) for Jylamvo (methotrexate) oral solution. The agency determined that the application cannot be approved in its current form, citing several deficiencies under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. Key issues identified primarily fall under product quality. A review of records from an unnamed manufacturing facility revealed objectionable conditions requiring satisfactory resolution, potentially through an inspection or adequate facility responses. Regarding the drug product, deficiencies included the omission of a Deliverable Volume test in specifications and insufficient stability data, with two out of six commercial batches failing to support the proposed 18-month expiration period. The FDA also requested additional stability data for specific batches, clarification on post-approval stability protocols, and appropriate in-use stability data for the 3-month open bottle period. Further actions required include revising the post-approval stability protocol to add a 15-month testing station and incorporating a commitment to withdraw non-compliant batches. The letter also highlighted necessary updates to prescribing information, carton and container labeling based on FDA revisions, and a comprehensive safety update detailing any significant changes in the safety profile, new adverse event data, and worldwide experience. Therakind Limited must address all listed deficiencies in a complete resubmission within one year to allow for a new review cycle.