Investigational medicinal products submitted over the course of 3 years and authorized at the Clinical Trials Office of the Italian Medicines Agency as part of a request for authorization of clinical trials were scrutinized to identify those encompassing nanomedicines. The quality assessment reports performed on the documentation submitted were analyzed, classifying and discussing the most frequently detected issues. The identification of nanomedicines retrieved and the information on their quality profiles are shared to increase the transparency and availability of information, providing feedback that can support sponsors in optimizing the quality part of the documentation and of the information submitted. Results confirm that nanomedicines tested as investigational medicinal products in clinical trials are developed and authorized in agreement with the highest standards of quality, meeting safety profiles according to the strong regulatory requirements in the European Union. Some key points are highlighted and indicate that the regulatory approach to innovation in a clinical trial setting could potentially be renewed to ride the wave of innovation, particularly in the nanotechnology field, capitalizing on lessons learned and still ensuring a strong and effective framework.