Digitalisation and automation in smart biomanufacturing: uncertainties, challenges and early pathways towards safe and sustainable design

Smart biomanufacturing is central to the European Union’s Green Deal ambitions, yet its integration of digital and autonomous technologies introduces complex uncertainties. While these technologies promise enhanced sustainability and efficiency, they also pose risks to integrity, equity, safety, and security that are poorly understood. Through surveys, workshops, and interviews within three Horizon Europe project consortia, this study captures multiple perspectives from automation, computer, and data science experts, and biotechnologists. Findings reveal recurring concerns around standardisation, infrastructure, error traceability, and sustainability paradoxes. We emphasise the critical role of cross-sectoral collaboration, interdisciplinary training, and maintained digital infrastructures to ensure smart biomanufacturing supports, rather than undermines, sustainability and societal goals. This study presents the first comprehensive scan of smart biomanufacturing challenges and proposes early strategic pathways towards responsible innovation in this transformative field. • Gaps in digitalisation standards, infrastructure and security persist and traverse disciplines. • Green transition tools may paradoxically increase sustainability and equity risks. • Automation and digitalisation risk loss of tacit knowledge and safety oversight. • Co-creation enables early risk detection in smart biomanufacturing innovation. • Regulation and frameworks ( e.g. , SSbD) must adapt to bio-digital convergence. • Shared FAIR infrastructures will prevent siloed and redundant data systems.