The 2022 revision of EU GMP Annex 1 marks the most significant overhaul of sterile manufacturing guidance in decades, driven by high-profile contamination events and a regulatory consensus that checklist-based compliance is no longer sufficient. It mandates a shift away from prescriptive rule-following toward risk-based, science-driven contamination control that manufacturers must design, justify, and continuously demonstrate. Yet a persistent gap remains between what Annex 1 requires and what facilities can actually show, as manual surface sampling, growth promotion testing, and endotoxin testing each introduce subjectivity and variability that undermine reproducibility. By confronting these real-world compliance failures, manufacturers can close the distance between intent and evidence, building programs capable of withstanding heightened regulatory scrutiny. Read the Article