FDA 483 - Sichuan Deebio Pharmaceutical Co., Ltd. - September 08, 2023

The FDA inspection of a drug substance manufacturing facility revealed numerous violations related to quality control, data integrity, and manufacturing processes. Laboratory records were not completed contemporaneously, lacked complete data, and the firm provided misleading information, delaying the inspection. Electronic test data for process validation batches of USP drug substance were unavailable, and undesirable test results were not reported or investigated, with retesting performed until in-specification results were obtained.

The quality control unit lacked responsibility for approving critical procedures. Method validation for residual solvent testing was inadequate, failing to identify additional peaks, which were later identified as impurities after a customer audit. No impurity profile studies or testing were performed for released drug substance. Supervisory oversight of laboratory electronic systems and data was deficient, with no procedures for manual chromatogram integration.

Production and process control procedures were inadequate, and process validation studies for USP drug substance were poorly designed, lacking scientific justifications for parameters like blend uniformity and in-process sampling. A customer complaint regarding inadequate blending and out-of-specification results for USP drug substance was linked to batches used in process validation. The practice of mixing multiple drug substance sublots was not evaluated for its impact on assay content. Studies on manufacturing process effects on biological and degradation control were not performed.

Investigations into discrepancies and out-of-specification results lacked conclusions and follow-up, and a complaint investigation did not adequately document sampling methods or implement corrective and preventive actions. Deficiencies identified by a customer audit, including data loss and unreported results, were not