Conventionally, designing of a technical system is completed in the product development phase in terms of all details and aspects. This can be done if the expected behavior and the conditions of operation are known in advance and can be validated before the product is launched on the market. Validation is typically based on a predictive analysis or simulation of the designed operation. However, this contradicts with the case of smart systems, such as smart cyber-physical systems (CPSs), which self-manage their operation or at least a part of it. Being able to adapt at run-time and evolve over time, smart CPSs cannot be validated using conventional deterministic approaches. This is especially true for smart CPSs used as instrumentation in the medical field. This gave the stimulation of our background research, the results of which are concisely summarized and critically concluded in this paper. The literature has been found fairly narrow in terms of novel validation approaches for self-managing smart systems. The main finding is that the tasks of operational and behavioral validation should be shared among the system designers and the designed systems. Designers need prognostic approaches, while systems need to construct validation plans and execute them at run-time. This needs validation-specific functionalities and context dependent mechanisms such as run-time validation frameworks or meta-models, objective-sensitive self-monitoring mechanisms, self-constraining and self-supporting mechanisms, and other enablers. Extensive foundational research and system prototype testing are deemed to be indispensable. To make the first small step in this direction, this paper proposes a concept for validation of smart medical CPSs. This relies on the following hypothesis: If a system has freedom for self-adaptation, then it should also be equipped with selfcontrol mechanism, meta-knowledge and a supervisory controller. It all together enables a purpose-and context dependent semantic reasoning about the operational and behavioral objectives. The paper suggests a number of topics for future research towards a run-time validation engine.