FDA EIR - Biogen MA Inc. - February 15, 2019

An FDA inspection of Biogen, Inc.'s facility in Research Triangle Park, NC, was conducted from February 7-15, 2019. This Level 2 CGMP inspection, part of the Team Biologics program and Compliance Program 7345.848 for Biological Drug Products, focused on the manufacture of Alprolix and Eloctate drug substances.

The inspection identified several significant Good Manufacturing Practice (GMP) violations. A primary concern was the failure to thoroughly investigate unexplained discrepancies and out-of-specification results. Biogen's deviation management system was found inadequate, often closing "Event" category deviations without proper root cause analysis, regulatory assessment, or corrective actions. Out-of-specification results were sometimes invalidated without conclusive laboratory root causes or subsequent manufacturing investigations. Furthermore, not all deviations requiring regulatory assessments were evaluated for Biological Product Deviation Reporting (BPDR) to the license holder, Bioverativ Therapeutics, Inc.

Other critical issues included insufficient controls over computer systems, leading to undocumented adjustments in master production records. Laboratory records were incomplete, with analytical equipment used in manufacturing not fully complying with data integrity requirements (e.g., 21 CFR Part 11). Equipment logbook reviews failed to capture discrepancies and inaccurate documentation of test results. Lastly, essential details were missing from periodic calibration records for critical laboratory equipment, as vendor reports lacked comprehensive calibration information.

At the conclusion of the inspection, an FDA-483 was issued to Biogen management. The company is required to provide a written response addressing each observation and outlining its planned corrective and preventive actions to rectify these deficiencies and ensure compliance with regulatory standards.