FDA 483 - PROVEPHARM Life Solutions - April 19, 2024

An FDA inspection conducted from April 15-19, 2024, at PROVEPHARM Life Solutions in Marseille, France, an Active Pharmaceutical Ingredient (API) manufacturer, identified significant deviations from current Good Manufacturing Practices (cGMP). The agency issued five observations, primarily highlighting inadequate quality system controls. A major concern was the firm's insufficient investigation into critical deviations and out-of-specification (OOS) results. A process validation batch of API exhibited OOS for a specific content, but the investigation lacked documented root cause analysis, involved unofficial retesting, and relied on non-validated spreadsheets. The batch was reprocessed without thoroughly identifying the root cause, and the initial OOS status was not transparently reported in the updated Certificate of Analysis submitted to the FDA. Additionally, uninvestigated unknown peaks were present in API batches, with a new peak appearing after reprocessing.

Further observations detailed failures in adhering to cGMPs for production and laboratory controls. Batch Manufacturing Records (BMRs) displayed numerous overwrites and instances of backdated entries, compromising data integrity. Chromatographic systems were standalone without central networking or data backup procedures. Crucially, the firm lacked established procedures for user access privileges and audit trail review for laboratory software (LabSolutions) and production HMI systems, indicating poor data governance. The inspection also revealed a lack of established equipment cleaning validation, missing procedures, unvalidated cleaning steps for non-dedicated equipment, and an absence of clean and dirty hold times. Lastly, the firm failed to conduct annual evaluations of reserve samples and omitted essential system suitability tests for chromatographic analysis, impacting the scientific soundness of laboratory controls. These findings necessitate comprehensive corrective actions to ensure product quality and regulatory compliance.