FDA CRL - Provention Bio

Provention Bio, Inc. received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA 761183) for PRV-031, submitted under section 351(a) of the Public Health Service Act. The FDA determined that the application cannot be approved in its current form due to several significant deficiencies across clinical pharmacology, product quality, and manufacturing facilities. Key issues include the failure of a pharmacokinetic bridging study (PRV-031-004) to demonstrate comparability between the clinical trial product and the planned commercial product, showing approximately a 44% lower AUC for the commercial version. Product quality concerns involve unacceptable charge variation in PRV-031 drug substance and drug product manufactured at AGC Biologics, inconsistency in stability behavior, and discrepancies compared to material manufactured by Eli Lilly. Further product quality deficiencies include a lack of information on Master Cell Bank and Working Cell Bank stability monitoring plans, a deficient Primary Reference Standard requalification protocol, and insufficient data regarding leachates from the container closure system. Additionally, recent inspections of a manufacturing facility revealed deficiencies that require satisfactory resolution. To address these, Provention Bio must establish PK comparability or justify its absence, investigate and remediate the source of charge variation, provide comprehensive cell bank stability protocols, revise the PRS requalification protocol, and submit sufficient leachate study data. Resolution of the manufacturing facility deficiencies and a comprehensive safety update are also required before potential approval.