FDA EIR - Grifols Therapeutics LLC - December 13, 2018

An FDA inspection of Grifols Therapeutics LLC in Clayton, NC, was conducted from December 4-13, 2018, under the Team Biologics program, adhering to Compliance Program CP 7345.848 for biological drug products manufactured under License #1871. The inspection revealed critical compliance issues. Primarily, there was a failure to thoroughly investigate unexplained discrepancies, particularly concerning adverse event trends for Gamunex-C lots. Pharmacovigilance requests for lot investigations were not adequately communicated or classified, leading to insufficient root cause analyses even after two Gamunex lots were recalled due to unexpected hypersensitivity reactions. The investigations performed were limited to batch record reviews, without additional analytical or source material assessment. Secondly, seven out of seven reviewed requalification training records for personnel performing visual inspection of filled products showed failing test results. These failures were not identified, resulting in no remedial training or product impact assessments, indicating inadequate visual inspection and training systems. Other observations included deficiencies in aseptic processing environmental monitoring systems, incomplete smoke studies for filling lines, and inadequate quality review processes for media fill records and environmental monitoring. At the inspection's conclusion, an FDA-483 was issued. Grifols management committed to expanded characterization testing for recalled lots, providing samples to the FDA, and conducting more thorough root cause investigations to address the identified quality and training system deficiencies.