FDA CRL - EYENOVIA INC

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Eyenovia, Inc. for its New Drug Application (NDA) for MYDCOMBI (tropicamide and phenylephrine hydrochloride ophthalmic spray), 1%/2.5%. The FDA could not approve the application due to several significant issues.

A primary concern was the drug product manufacturing facility's non-compliance with current Good Manufacturing Practice (CGMP) regulations (21 CFR parts 210 and 211), identified during a recent inspection. The FDA requires satisfactory resolution of these deficiencies, as stability data from a non-compliant facility may be insufficient.

Furthermore, the application lacked adequate safety tests for the drug. Specifically, the microbial ingress container closure integrity testing did not sufficiently demonstrate the product's ability to withstand a worst-case microbial challenge. The FDA also highlighted the need for clarification and validation regarding hold time studies and other specific validation information.

A key regulatory development impacting the application is the FDA's classification of MYDCOMBI as a drug-led combination product, based on the recent Genus decision. This means the product, which includes an ophthalmic dispenser, must comply with CGMP requirements for both drug (21 CFR parts 210, 211) and device (21 CFR part 820 Quality System regulation) constituent parts, potentially through a streamlined approach outlined in 21 CFR part 4. Eyenovia must update its application to reflect this combination product status and ensure device-related quality system information is available for inspection.

Additional device-specific issues included the need to clarify the device's electrical components and reusability. Crucially, the FDA required comprehensive validation testing, including shipping and transit (ASTM D4169), actuation force, leak, and performance testing to ensure consistent and safe drug delivery. Resolution of all identified deficiencies is required for approval.