The objective of this Safety Guide is to provide recommendations for the design of new nuclear power plants related to defense in depth and the practical elimination of plant event sequences that could lead to an early radioactive release or a large radioactive release. It also provides recommendations in relation to design aspects of defense in depth, in particular on those aspects associated with design extension conditions. Since the introduction of the term "practical elimination" in the early 90's and the recognition that accident conditions could include design extension conditions without significant fuel degradation and design extension conditions with core melting, those topics have been the subject of extensive discussions and several publications. The purpose of this publication is to facilitate international consensus on the understanding of those topics among regulators and designers and to provide recommendations for their consistent implementation in relevant nuclear power plant designs. In particular, this Specific Safety Guide gives recommendations related to the demonstration of the implementation of the practical elimination concept for those plant event sequences that could lead to an early radioactive release or a large radioactive release, which relies on the physical impossibility or on the high-level confidence that they are extremely unlikely to arise.