Healthcare systems around the world are undergoing an organizational, methodological and technological transformation towards personalized, preventive, predictive, participative precision (5P) medicine ecosystems. These ecosystems consider individual health status, conditions, genetic and genomic dispositions in personal social, occupational, environmental, and behavioural contexts. For designing and managing the resulting highly interdisciplinary, complex, distributed and dynamic ecosystem, we must formally and consistently represent the system and its components at necessary granularity levels from the perspective of all actors including the subject of care. As those actors from different domains have different education, skills, and experiences, using different methodologies, languages and terminologies, communication and cooperation, i.e. interoperability, must advance from the data level (data sharing) to the knowledge level (knowledge sharing). To understand the business system, it must formally represent each considered use case structurally and functionally. Therefore, the design, implementation and management of intelligent and ethical transformed ecosystems must be realized, using a system-theoretical, architecture-centred, ontology-based and policy-driven approach, developed by the author over the last 30 years. The related model and framework has been meanwhile standardized, written by the author, as the ISO 23903 Interoperability and Integration Reference Architecture and is used in many standards and projects of ISO, CEN, IEC, IEEE, OMG, HL7 etc. Meanwhile, the standard is defined as mandatory for any specification or project at ISO/TC215 and CEN/TC251, addressing more than one domain. Thereby, it manages also security, privacy and trust in detail. The Keynote introduces necessary standards and methodologies for designing and managing 5P medicine ecosystems as well as practical examples. The presented approach is deployed in multiple domains beyond health and social care, such as nanotechnology, astrophysics, environmental sciences, education, etc.