FDA EIR - BioMarin Pharmaceutical, Inc. - December 14, 2017

An FDA comprehensive surveillance and biological pre-license inspection of BioMarin Pharmaceutical, Inc. in Novato, CA, was conducted from December 4 to December 14, 2017. The inspection, performed under cGMP guidelines and specifically Compliance Program Guidance Manuals 7356.002M and 7346.832 for BLA 761079 (Pegvaliase Bulk Drug Substance), focused on Quality, Laboratory Control, Facilities and Equipment, and Production Systems. The inspection concluded with the issuance of a 10-item FDA Form 483, detailing significant deficiencies. Key violations included widespread failures in documentation, such as not recording laboratory equipment use in real-time and inadequate pH meter calibration procedures for in-process materials. The quality control unit demonstrated insufficient oversight, evidenced by approving a change request without complete data and failures to adequately determine root causes or implement effective corrective and preventive actions (CAPAs) for deviations and investigations. Furthermore, BioMarin was deemed unprepared for commercial manufacturing of Pegvaliase, as critical process and cleaning validations remained incomplete. Other issues involved the lack of procedures and technical data for disinfectant spray bottles and the failure to clean manufacturing equipment. BioMarin Pharmaceutical, Inc. management acknowledged the observations and committed to submitting a written response to the FDA San Francisco District Office within 15 business days, outlining their planned corrective actions.