FDA CRL - Santen Inc

The FDA issued a Complete Response Letter (CRL) to Santen, Inc. regarding their New Drug Application (NDA 215092) for Omlonti (omidenepag isopropyl ophthalmic solution), 0.002%. The primary reason for non-approval stems from unresolved deficiencies related to current good manufacturing practice (cGMP) regulations (21 CFR parts 210 and 211) at the Woodstock Sterile Solutions manufacturing facility, identified during a recent inspection. These conditions were deemed insufficient to assure the drug product's identity, strength, quality, purity, stability, and bioavailability. Satisfactory resolution and subsequent FDA verification of these manufacturing issues are required.

Additionally, the agency found the clinical investigations inadequate to demonstrate the drug's safety. A study showed significant corneal endothelial cell loss in patients receiving omidenepag isopropyl monotherapy, indicating potential harm. Santen is mandated to conduct and submit a new 12-month, concurrently controlled, randomized clinical study comparing omidenepag isopropyl monotherapy to a control without the drug, specifically monitoring corneal endothelial cell counts.

Further, the FDA clarified that Omlonti is now classified as a drug-led combination product. This requires compliance with cGMPs for both drug (21 CFR parts 210, 211) and device (21 CFR part 820) components, including proper documentation on FDA Form 356h. Santen must address all identified issues, submit a comprehensive safety update, and provide revised labeling within one year.