Unresolved Manufacturing and Testing Facility Deficiencies
Severity: criticalDuring a review of records requested under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act, the FDA communicated issues with the manufacturing facility named in your application. Satisfactory resolution of the remaining issues is required before this application may be approved. An inspection of the manufacturing facility is required before the application can be approved to ensure compliance with CGMP. Additionally, during a recent inspection of the testing facility, deficiencies were conveyed to the representative. Satisfactory resolution of these deficiencies is also required. Documentation of communications with the Agency to facilitate resolution of all observed objectionable conditions is requested.
Recommended response: Address all manufacturing and testing facility issues identified during records review and inspections. Provide documentation of communications with the agency regarding resolution and ensure both facilities are ready for required pre-approval inspections, considering current travel restrictions and FDA guidance.
Cited: section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This update must include data from all nonclinical and clinical studies/trials, detailing any significant changes in the safety profile. It requires new safety data from studies/clinical trials for the proposed indication, tabulations combining new and original data, and comparative tables of adverse event frequencies. Separate tables for adverse events in other indications, retabulation of premature trial discontinuations, case report forms and narrative summaries for deaths/serious adverse events, updated exposure information, a summary of worldwide safety experience, and English translations of foreign labeling are also required.
Recommended response: Compile a comprehensive safety update including all nonclinical and clinical data, detailed analysis of safety profile changes, updated adverse event tabulations, reasons for trial discontinuations, case report forms/narratives for deaths/serious adverse events, updated exposure information, worldwide safety experience, and English translations of foreign labeling, as per 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Labeling Comments Reserved Pending Application Adequacy
Severity: minorComments on the proposed labeling are reserved until the application is otherwise adequate. Upon resubmission, reference the draft labeling submitted on June 30, 2021. Review of FDA's labeling resources, regulations, and guidance documents, including the Pregnancy and Lactation Labeling Final Rule and Selected Requirements for Prescribing Information (SRPI), is encouraged.
Recommended response: Review and update the proposed labeling in accordance with FDA's Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule, referencing the June 30, 2021, draft upon resubmission.
Proprietary Name Resubmission Required
Severity: minorThe proposed proprietary name, LIQREV, was found acceptable pending approval of the application in the current review cycle. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proprietary name 'LIQREV' along with the response to other application deficiencies.
