Unresolved Manufacturing Facility Deficiencies
Severity: majorIssues identified during a Remote Regulatory Assessment (RRA) and pre-license inspection (PLI) at the drug substance manufacturing facility remain unsatisfactorily resolved. Satisfactory responses are required prior to submitting a complete response, and a re-inspection may be necessary.
Recommended response: Work closely with the manufacturing facility to address and resolve all identified deficiencies. Provide comprehensive and satisfactory responses to the inspection team, including the date of the facility’s response to the FDA Form 483, before resubmitting the application.
Data Reliability Concerns and Comparability Issues
Severity: criticalConcerns exist regarding the reliability of data generated at the manufacturing facility, which impacts the comparability between commercial and clinical materials. This prevents determination of the adequacy of the proposed drug substance manufacturing process and overall control strategy.
Recommended response: Engage an independent third party to develop a protocol for, and conduct, a comprehensive assessment of the impacted information and data. Confirm the protocol's adequacy with FDA. If data are removed or control strategy changes are made, provide reliable and accurate additional information and data (e.g., testing results from repeated studies).
Prescribing Information and Carton/Container Labeling Comments Reserved
Severity: minorFDA reserves comment on the proposed prescribing information and carton/container labeling until the application is otherwise adequate. The sponsor is encouraged to review available labeling resources.
Recommended response: Review FDA's Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites to prepare for future labeling negotiations once other critical deficiencies are resolved.
Proprietary Name Resubmission Required
Severity: infoThe proposed proprietary name, Ebglyss, was conditionally acceptable. However, it must be resubmitted once all other application deficiencies identified in this letter have been addressed.
Recommended response: Resubmit the proposed proprietary name request only after all other deficiencies outlined in this Complete Response Letter have been fully resolved and addressed.
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), is required when responding to the deficiencies. This includes specific requirements for presenting new safety data, tabulations, comparisons, case report forms for deaths/discontinuations, summaries of serious adverse events, updated exposure information, and worldwide safety experience.
Recommended response: Prepare a detailed safety update strictly adhering to the requirements of 21 CFR 314.50(d)(5)(vi)(b), ensuring all specified data presentations, summaries, and analyses are included.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Process Validation Data for Pre-filled Syringe Needle Safety Device
Severity: majorA re-evaluation of the process validation data for the pre-filled syringe needle safety device (PFS-NSD) drug product manufacturing process is required.
Recommended response: Conduct a thorough re-evaluation of the process validation data for the PFS-NSD manufacturing process and submit the updated information.
