An ITS represents a Cyber-Physical System (CPS), which will involve information exchange at operational level as well as potential explicit collaboration between separate entities (systems of systems). Specific emphasis is required to manage the complexity and safety of such future CPS. In this paper we focus on model-based approaches for these purposes for analyzing and managing safety throughout the lifecycle of ITS. We argue that: (1) run-time risk assessment will be necessary for efficient ITS; (2) an information centric approach will be instrumental for future ITS to support all aspects of safety management – a “safety loop”; (3) a formal basis is required to deal with the large amounts of information present in an ITS. We elaborate these arguments and discuss what is required to support their realization.