Bristol-Myers Squibb Company – FDA 483, Jul 8, 2025

An FDA inspection from June 16 to July 8, 2025, at Bristol-Myers Squibb Company's Devens, MA facility, a biologic drug substance manufacturer, revealed significant deviations from Good Manufacturing Practices. The observations centered on four key areas requiring corrective action. First, environmental controls were inadequate. The facility experienced repeated mold contamination (Penicillium, Aspergillus, Cladosporium species) in critical Grade 5 manufacturing areas and non-sterile storage rooms. Visible mold on surfaces, HVAC, and even product containers was noted, yet the root cause for recurring contamination remained unaddressed, and affected materials/rooms continued in use. Disinfection procedures for materials entering sterile areas were also found insufficient. Second, critical equipment qualification was deficient. Chemistry analyzers, used for essential cell culture parameters, lacked proper Performance Qualification. A flawed equivalency study led to a biased correction factor and a terminated drug substance batch. Additionally, a sterilization-in-place process had an undocumented failure during its qualification, which was not re-evaluated after adjustments. Third, raw material quality controls were unsound. The firm noted approximately 40 deviations for atypical particulates (e.g., proteinaceous, iron oxide) in a crucial raw material. Instead of thorough investigation, only affected drums were rejected, with other containers from the same problematic lot used for production, leading to the release of potentially compromised drug substance batches. Finally, deviation and component failure investigations were insufficient. Out-of-range pH measurements for buffers lacked documented root cause analysis. Procedures for preparing solutions were also inadequate, as quality events were not consistently initiated for discarded solutions failing release criteria, preventing the determination of failure causes. Bristol-Myers Squibb must implement robust corrective and preventive actions to ensure compliance and product quality.