FDA CRL - IBSA Institut Biochimique SA

The FDA issued a Complete Response Letter (CRL) to Institut Biochimique SA (IBSA) regarding its New Drug Application (NDA 206976) for diclofenac epolamine topical system 1.3%, initially submitted on May 26, 2016. The application, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, cannot be approved due to several deficiencies across clinical, nonclinical, and biopharmaceutical areas.A primary issue is the lack of sufficient data to bridge the product used in clinical studies with the product intended for commercialization, which is manufactured at a different site. IBSA must conduct a new, adequate, and well-controlled clinical efficacy and safety trial using the product from the proposed commercial manufacturing facility.Nonclinical concerns involve inadequate safety justification for unidentified leachable compounds exceeding the 5 mcg/day qualification threshold. IBSA needs to identify these compounds, provide a comprehensive toxicological risk assessment, or demonstrate their inability to penetrate the skin.The company's risk-based approach to support the manufacturing site change was deemed inadequate. Consequently, an in vivo bridging study—specifically, a new clinical efficacy and safety trial—is required, as per SUPAC-MR guidance, due to the unavailability of unexpired drug product from the original site for a direct pharmacokinetic comparison.Other required actions include demonstrating the discriminating ability of a specific quality control method, providing a comprehensive safety update, and submitting revised prescribing information in structured product labeling (SPL) format. The previously acceptable proprietary name, "Licart," also requires resubmission. This CRL necessitates significant additional data and studies to demonstrate the safety, effectiveness, and quality of the proposed drug product from the new manufacturing site.