Issued January 1, 2022
Issued
January 1, 2022
Application
Other • 215092
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response letter from the FDA to Santen, Inc. regarding their New Drug Application (NDA) for Omlonti (omidenepag isopropyl ophthalmic solution), 0.002%. The FDA has determined that the application cannot be approved in its present form due to several deficiencies, including manufacturing facility issues, inadequate clinical safety data regarding corneal endothelial cell loss, and requirements related to the product's classification as a drug-led combination product. The letter outlines specific actions and information required for resubmission and potential approval.
The application for Omlonti cannot be approved due to significant manufacturing deficiencies at the drug product facility, inadequate clinical safety data regarding corneal endothelial cell loss requiring a new 12-month study, and issues related to the product's classification as a combination product requiring updated regulatory compliance and CGMP adherence. Additionally, administrative issues such as proprietary name resubmission, a comprehensive safety update, and an unacceptable analytical testing site withdrawal need to be addressed.
The manufacturing facility (Woodstock Sterile Solutions) does not comply with current good manufacturing practice regulations (21 CFR parts 210 and 211). Satisfactory resolution and FDA verification are required before approval.
Recommended response: Address all deficiencies identified during the inspection and ensure satisfactory resolution and FDA verification.
Cited: parts 210, parts 211
Study 1171504 demonstrated significant endothelial cell loss. The absence of a control arm without omidenepag isopropyl suggests potential harm. A new 12-month concurrently controlled, randomized clinical study comparing corneal endothelial cell counts to a control without the drug is required.
Recommended response: Conduct and submit a new 12-month concurrently controlled, randomized clinical study as described.
Cited: section 505(b) of the Federal Food, Drug, and Cosmetic Act
The proposed proprietary name, Omlonti, was conditionally acceptable pending approval. It needs to be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name with the complete response.
Cited: 21 CFR 314.50(l)(1)(i)
A safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), must be included when responding to deficiencies, covering data from all nonclinical and clinical studies/trials.
Recommended response: Prepare and submit a comprehensive safety update as per regulations.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The product is now regulated as a drug-led combination product. The applicant must indicate combination product status on Form 356h, include all relevant manufacturing facilities (including design control for device part), and demonstrate compliance with CGMP for combination products (21 CFR part 4), either streamlined or full compliance with 21 CFR parts 210, 211, and 820. Information on device QS regulation compliance must be available for inspection.
Recommended response: Update Form 356h, ensure all relevant facilities are listed, and prepare documentation demonstrating compliance with combination product CGMP regulations (21 CFR part 4) for inspection.
Cited: section 201(h) of the FD&C Act, 21 CFR part 4, 21 CFR parts 210, 21 CFR parts 211, 21 CFR part 820
The proposal to withdraw an analytical testing site and commit to a post-approval supplement is not acceptable. A facility for drug product release and stability testing is required prior to approval. An alternative facility must be proposed.
Recommended response: Propose an alternative facility for drug product release and stability testing before resubmission.
The primary themes are critical manufacturing quality issues, a significant clinical safety concern requiring further study, and the need to adapt to new regulatory requirements for combination products, alongside several administrative and quality control deficiencies.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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