Fresenius Kabi AG – FDA Warning Letter, Sep 24, 2022

The FDA issued a Warning Letter to Fenwal International, Inc. (a Fresenius Kabi company) following an inspection from September 12-24, 2022, at their Maricao, PR facility. The inspection revealed significant deviations from current Good Manufacturing Practice (CGMP) requirements for blood-pack units and component solutions, violating Section 501(a)(2)(B) of the FD&C Act and 21 CFR, Parts 210 and 211. Key violations include the failure to thoroughly investigate unexplained discrepancies and batch failures, particularly concerning numerous bioburden excursions and 'too numerous to count' (TNTC) results, a repeat deficiency from prior inspections. The firm also failed to test in-process materials and reject non-conforming lots, establish procedures to prevent microbiological contamination, and adequately validate sterilization processes for high bioburden levels. Equipment was not properly cleaned and maintained, and the facility itself was not in a good state of repair, with issues like holes in HEPA boxes, residue, and structural damage. Additionally, laboratory controls were found to be scientifically unsound, with erroneous sterility assurance level (SAL) calculations for TNTC results and inadequate bioburden test method validation. The FDA noted that the firm's corrective actions submitted in response to the Form FDA-483 were insufficient, failing to address recurring violations. These CGMP deviations pose a significant risk of microbial contamination, with organisms previously recovered matching isolates from clinical septic reactions. The FDA requires a written response within 15 working days detailing corrective actions and prevention strategies, warning of potential regulatory actions like seizure or injunction if issues are not adequately resolved.