FDA CRL - Pfizer Pharmaceuticals, LLC

Fera Pharmaceuticals, LLC received a Complete Response Letter from the FDA regarding its New Drug Application (NDA 202408) for Avaclyr (acyclovir ophthalmic ointment) 3.0%, submitted under section 505(b)(2). The FDA determined that the application cannot be approved in its current form due to insufficient information to establish a scientific “bridge” between Fera’s proposed product and the product used in published clinical trials to determine safety and efficacy for acute herpetic keratitis. Key deficiencies highlighted include inadequate characterization of petrolatum, requiring comparative analysis of specific quality and performance attributes against a nominal Reference Listed Drug (RLD). The FDA also noted the need for comprehensive viscosity profile measurements, including both linear and nonlinear behavior. Further, the application lacks sufficient quality and performance tests, with recommendations for specific USP methods and validation of the In Vitro Release Test (IVRT). Deficiencies also extend to the inadequate description and comparative analysis of acyclovir particle size (D10, D50, D90) and the characterization of acyclovir polymorphic forms in Fera’s product compared to the RLD. To address these issues, Fera Pharmaceuticals must conduct extensive comparative analyses of its product's quality attributes with the nominal RLD. As an alternative, the FDA suggested conducting a controlled clinical trial. The company is also required to submit a comprehensive safety update and revised labeling once the primary deficiencies are resolved.