FDA EIR - Astellas Pharma US Inc. - October 04, 2019

An FDA surveillance inspection of Astellas Pharma US, Inc. in Northbrook, IL, conducted from September 30 to October 4, 2019, identified two significant observations related to bioanalytical data integrity and record-keeping. The inspection focused on records for a post-marketing supplement (NDA 021506/S023) study, originally performed at the now-closed Astellas Research Institute of America (ARIA) Skokie facility. The first observation cited undocumented and unjustified modifications of chromatographic integration parameters during method validation for micafungin and its metabolite. Crucially, original records of these modifications were not retained, preventing an assessment of their impact on study results. The second observation highlighted the firm's failure to document the receipt conditions of crucial stock solutions (micafungin, M5, and an internal standard) following prolonged transit from Japan. These undocumented solutions were subsequently utilized in both method validation and sample analyses, raising concerns about data reliability. Conducted under Compliance Program 7348.004 for In Vivo Bioavailability/Bioequivalence Studies (Analytical), the inspection concluded with the issuance of a Form FDA 483. Astellas management acknowledged the observations and committed to a written response within 15 business days. No specific corrective actions for the original issues were proposed by the firm, as the analytical lab responsible had ceased operations and Astellas now outsources such work. The FDA also emphasized the need for more comprehensive and readily available study documentation.