Unresolved CGMP Deficiencies at Manufacturing Facility
Severity: criticalFDA conveyed deficiencies to the representative of the manufacturing facility during a CGMP inspection. Satisfactory responses to the FDA 483 are required, and compliance with CGMP must be determined, potentially requiring re-inspection. Satisfactory outcomes of both pre-approval inspection (PAI) and CGMP surveillance inspections will be needed prior to approval.
Recommended response: Address all outstanding CGMP deficiencies with the manufacturing facility, provide satisfactory responses to the FDA 483, and ensure readiness for potential re-inspection and PAI.
Inadequate Prescribing Information (PI) Content and Format
Severity: majorThe draft labeling is not responsive to previous electronic communication. Formatting errors need correction using the Selected Requirements of Prescribing Information (SRPI) checklist. Updated content of labeling in Structured Product Labeling (SPL) format is required, conforming to 21 CFR 201.56(a) and (d) and 201.57.
Recommended response: Revise the Prescribing Information to address all formatting and content issues, ensuring compliance with 21 CFR 201.56(a), (d), and 201.57, and submit in SPL format.
Cited: 21 CFR 314.50(l)(1)(i), 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57
Deficiencies in Carton and Container Labeling
Severity: majorDraft carton and container labeling needs revision based on agency recommendations. Specifically, the Medication Guide (MG) statement on the carton labeling is not on the principal display panel (PDP) as required by 21 CFR 208.24(d). The container label also omits the container closure term (e.g., 'vial').
Recommended response: Update carton and container labeling to ensure the Medication Guide statement is prominently displayed on the PDP and include the container closure term on the container label, adhering to 21 CFR 208.24(d).
Cited: 21 CFR 208.24(d)
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), is required upon resubmission. This includes detailed changes in safety profile, new safety data from studies/trials, tabulations of combined data, comparison tables, separate tables for other indications, retabulation of premature trial discontinuations, case reports for deaths/SAEs, information on changes in common adverse events, updated exposure information, worldwide safety experience summary, and English translations of foreign labeling.
Recommended response: Prepare and submit a comprehensive safety update in accordance with 21 CFR 314.50(d)(5)(vi)(b), incorporating all new clinical and nonclinical safety data.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Inadequate Instructions for Use (IFU) for Vyafuser Delivery System
Severity: majorThe patient and healthcare provider Instructions for Use (IFU) for the Foscarbidopa and Foslevodopa Delivery System (Vyafuser) does not include recommended information outlined in the 'Infusion Pumps Total Product Life Cycle' guidance. Specifically, it lacks information regarding factors affecting flow accuracy like head height or backpressure, and performance testing to support claims about these factors was not found in the submission.
Recommended response: Revise the Vyafuser IFU to include comprehensive information on factors affecting flow accuracy (e.g., head height, backpressure) and provide supporting performance testing data as recommended by FDA guidance.
Proprietary Name Resubmission Required
Severity: minorThe proposed proprietary name, Vyalev, was found acceptable pending approval in the current review cycle. It needs to be resubmitted with the complete response.
Recommended response: Resubmit the proprietary name 'Vyalev' with the complete response.
