FDA 483 - Brigham and Women's Hospital - September 16, 2021

Brigham and Women's Hospital received an FDA Form 483 following an inspection from August 5 to September 16, 2021, highlighting significant concerns regarding their manufacturing operations and adherence to Current Good Manufacturing Practices (cGMP). Key violations included a systemic failure to investigate numerous environmental monitoring excursions within ISO-5 and ISO-7 classified areas between June and November 2020, despite the recovery of objectionable microorganisms and ongoing production. The hospital also failed to implement previously identified corrective measures. Facilities were found inadequate, with repeated water intrusions in cleanroom areas, an active leak in raw material storage, and uncontrolled high humidity in production suites, all contributing to contamination risks. Investigations into these issues were deemed insufficient, and comprehensive facility remediation is still pending until February 2022. Furthermore, laboratory testing procedures were cited for an inadequate Out-of-Specification (OOS) investigation process, relying on repetitive testing rather than thorough root cause analysis. A repeat observation from 2019 noted non-compliance with quality assurance procedures regarding media fill simulations, with personnel manufacturing products without completing required validations. Finally, equipment validation and maintenance were deficient, specifically with incorrect sporicide contact times and inadequate qualification/requalification of incubators critical for environmental and sterility testing. Corrective actions are required to address these deficiencies and ensure product quality and patient safety.