Inadequate Human Factors Validation Study
Severity: criticalBased on the results of the human factors (HF) validation study data, root cause analysis, and participants’ subjective feedback, the proposed product design and user interface do not support safe and effective use of the product. The agency previously communicated concerns regarding the HF study results report.
Recommended response: Implement HF protocol recommendations stated in the HF validation study protocol advice letter dated February 26, 2021, consider additional design modifications and labeling changes, and submit the results of another HF validation study to demonstrate safe and effective use.
Required Facility Inspections Not Conducted
Severity: criticalInspections of PharmaEssentia Corporation facilities (FEI 2000012832, Taichung, Taiwan and FEI 3005182038, Taipei, Taiwan) are required to assess compliance with CGMP before the application can be approved. Due to travel restrictions, these inspections could not be conducted during the current review cycle.
Recommended response: Address other deficiencies while awaiting the FDA's ability to conduct required facility inspections once travel restrictions are lifted and based on public health need.
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update is required as described at 21 CFR 314.50(d). This update must include data from all nonclinical and clinical studies/trials, describe significant changes in the safety profile, present new and combined safety data, provide comparative tables of adverse event frequencies, retabulate premature trial discontinuations, provide case report forms and narrative summaries for deaths and serious adverse events, describe changes in common adverse events, provide updated exposure information, and summarize worldwide experience including foreign labeling translations.
Recommended response: Compile and submit a comprehensive safety update including all new nonclinical and clinical data, detailed analyses, and worldwide experience, following the specific requirements outlined in the letter, particularly 21 CFR 314.50(d).
Cited: 21 CFR 314.50(d)
Proprietary Name Resubmission
Severity: infoThe proposed proprietary name, Besremi, was found acceptable pending approval of the application in the current review cycle. It needs to be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name 'Besremi' with the complete response to the application deficiencies.
Bioburden and Sterility Test Method Suitability Data
Severity: minorAdditional data is needed for in-process bioburden and sterility test method suitability. Three batches should be used for testing method suitability in the bacteriostasis/fungistasis assay, but only two batches were provided for bioburden and one for sterility. Provide results from one additional batch for in-process bioburden and two additional batches for sterility test method suitability.
Recommended response: Provide bioburden and sterility test method suitability results for the required number of additional batches as recommended by the agency.
