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With the modernization of existing analog instrumentation and control (I&C) systems in nuclear power plants through digital I&C technology, and the implementation of digital I&C systems in new plants, the industry is faced with significant challenges. These challenges appear in the form of difficulties in managing the necessarily incremental transition, highly integrated (and interdependent) architectures, the flexible configurability enabled by digital technology, and uncertainty and inconsistency in licensing digital I&C systems and equipment in the different Member States. This publication discusses 17 major issues that utilities, developers, suppliers and regulatory stakeholders need to consider, so that the industry can capture and benefit from shared experience, recent technological developments, and emerging best practices.