FDA CRL - Galephar Pharmaceutical Research Inc.

The FDA issued a Complete Response Letter (CRL) to Galephar Pharmaceutical Research Inc. for its New Drug Application (NDA 215040), submitted July 7, 2022, for Legubeti (acetylcysteine) oral solution under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application was deemed unapprovable due to several critical deficiencies.

Key clinical issues include inadequate data demonstrating the tolerability of Legubeti, the lysine salt of acetylcysteine, across the full range of proposed doses and patient body weights. Concerns were raised regarding the product's palatability and potential impact on patient compliance, which could elevate the risk of acetaminophen-induced toxicity. Additionally, the submission lacked sufficient information to support the safety of L-lysine administration in pediatric patients weighing as low as 1 kg, given that the proposed dosage exceeds estimated daily L-lysine intake for this vulnerable population.

A regulatory issue identified pertains to the reliance on the listed drug Mucomyst while referencing Cetylev prescribing information for Physician Labeling Rule (PLR) and Pregnancy and Lactation Labeling Rule (PLLR) compliance. Galephar must either provide original publications to substantiate its proposed labeling language or adhere to specific legal and regulatory requirements if relying on FDA's safety and effectiveness findings for Cetylev.

To resolve these deficiencies, Galephar must conduct palatability and tolerability studies utilizing a validated patient-reported outcomes instrument, furnish additional data to justify L-lysine safety in pediatric patients, and clarify its reliance strategy for listed drug information. A comprehensive safety update and revised labeling in structured product labeling (SPL) format are also mandated for resubmission.