Ultragenyx Pharmaceutical Inc. – FDA 483, Apr 25, 2025

During an inspection from April 21-25, 2025, the FDA issued a Form 483 to Ultragenyx Pharmaceutical Inc., a drug product manufacturer in Bedford, MA. The inspection revealed significant observations concerning adherence to Good Manufacturing Practices. Key issues included pervasive data integrity deficiencies, such as the unauthorized destruction of controlled GMP documents, use of unofficial batch records, and inaccurate uncontrolled logbooks. The facility also exhibited inadequate maintenance, with instances of damaged flooring, un-documented leaks, and improperly cleaned aseptic processing equipment, which were not properly documented or investigated. Furthermore, deviation management was deemed insufficient, characterized by inadequate root cause investigations for recurring contamination, a failure to escalate repeated minor deviations, and improper classification of critical incidents. Quality oversight was found to be deficient, evident from unapproved aseptic process simulations performed without quality approval and undocumented aborted environmental monitoring tests. Lastly, procedures for preventing microbiological contamination were inadequate, highlighted by insufficient smoke studies for critical airflow patterns and unsanitary conditions, like uncleaned equipment moved between classified areas. Ultragenyx is required to respond with comprehensive corrective actions to address these serious compliance concerns.