Brigham and Women’s Hospital Inc. – FDA Warning Letter, Sep 16, 2021

The FDA inspected Brigham and Women’s Hospital Inc. in Boston, MA, from August 5 to September 16, 2021, identifying significant Current Good Manufacturing Practice (CGMP) violations for positron emission tomography (PET) drugs, rendering their products adulterated under 21 U.S.C. 351(a)(2)(B). Key deficiencies included inadequate facilities for preventing contamination (21 CFR 212.30(a) and (b)), evidenced by water infiltrations and fungal recoveries in ISO 5 environments, and a failure to adequately follow procedures for equipment suitability. The firm also failed to ensure operators completed media fill qualifications within established periods, a repeat observation from a prior inspection. Furthermore, the hospital did not adequately investigate ISO 5 environmental monitoring results exceeding action levels or implement effective corrective actions. A critical violation involved the failure to conduct adequate investigations and take appropriate corrective action for multiple out-of-specification (OOS) endotoxin results, specifically for [13N]-Ammonia for Injection (21 CFR 212.20(d)). The FDA deemed the firm's responses inadequate, particularly regarding facility remediation plans and OOS investigation procedures. The agency strongly recommended engaging a CGMP consultant. The firm must respond within 15 working days with comprehensive corrective actions and recurrence prevention plans, including specific details on facility controls, personnel, and retrospective OOS evaluations. Failure to comply may result in further regulatory action, including seizure, injunction, and impact on future approvals or export certificates.