VPH-HF: A software framework for the execution of complex subject-specific physiology modelling workflows

•Presentation of new open source software, the VPH Hypermodelling Framework (VPH-HF), which overcomes the limitations of most workflow execution environments.•The Computational overhead of VPH-HF is small, and tends to be flat regardless of the complexity and the computational cost of the hypermodel being executed.•VPH-HF also provide an automatic caching system over the execution of every hypomodel, which may provide considerable speed-up when the orchestration is run repeatedly over large numbers of patients or within stochastic frameworks, and the input sets are properly binned.•The caching system also makes it easy to form large input set/output set databases required to develop reduced-order models, and the framework offers the possibility to dynamically replace single models in the orchestration with reduced-order versions.