Issued January 1, 2023
Issued
January 1, 2023
Application
Other • 211746
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This document is a Complete Response Letter from the FDA to Glenmark Pharmaceuticals, Inc. regarding their New Drug Application (NDA) 211746 for GSP 301 (olopatadine HCl and mometasone furoate) 665 mcg/25 mcg Nasal Spray. The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to facility inspections, product quality, and requirements for prescribing information and safety updates.
The application cannot be approved in its present form due to objectionable conditions observed at the manufacturing facility, an inadequate drug master file, unresolved product quality issues related to stability and extractables/leachables, and the need for a comprehensive safety update and revised labeling.
During a recent inspection of the Glenmark Pharmaceuticals Ltd manufacturing facility, objectionable conditions were observed. Satisfactory resolution of these observations is required before approval.
Recommended response: Address and resolve all objectionable conditions observed during the manufacturing facility inspection and provide evidence of satisfactory resolution to the agency.
A supporting drug master file has been reviewed and found to be inadequate. Deficiency comments have been forwarded to the holder of this file.
Recommended response: Ensure the DMF holder addresses all deficiencies identified by the agency and provides an updated, adequate DMF.
Provide the stability results for the 30-month (25°C/60% RH) time-point for your registration batches to assure that all acceptance criteria are met and potential leachables are absent or below levels of safety concern. Provide an updated extractable and leachable correlation, if applicable.
Recommended response: Submit 30-month stability data for registration batches, confirm all acceptance criteria are met, and provide an updated extractable and leachable correlation to ensure product safety.
Provide the validation data for the routine HDPE bottle extractables method and a description of the development of extractables acceptance criteria for the HDPE bottle.
Recommended response: Submit comprehensive validation data for the HDPE bottle extractables method and detail the development of acceptance criteria for extractables from the HDPE bottle.
The agency reserves comment on the proposed labeling until the application is otherwise adequate. An updated content of labeling in structured product labeling (SPL) format, compliant with 21 CFR 314.50(l)(1)(i), is required.
Recommended response: Revise and resubmit the proposed labeling in SPL format, ensuring compliance with PLR requirements and the Pregnancy and Lactation Labeling Final Rule, once other deficiencies are addressed.
Cited: 21 CFR 314.50(l)(1)(i)
The proposed proprietary name, RYALTRIS, was found acceptable pending approval. It needs to be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name, RYALTRIS, with the complete response to the application deficiencies.
A comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), is required. This includes data from all nonclinical and clinical studies, detailed analysis of safety profile changes, retabulation of adverse events, and case report forms/narrative summaries for deaths and serious adverse events.
Recommended response: Provide a comprehensive safety update including all new nonclinical and clinical data, detailed analysis of safety profile changes, retabulation of adverse events, case report forms for deaths and serious adverse events, and updated exposure information, as per 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The application received a Complete Response Letter primarily due to critical manufacturing facility issues, significant product quality deficiencies related to stability and extractables, and the need for a thorough safety update and revised labeling to meet regulatory standards.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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