Nanotechnologies are characterized by a growing legacy of already marketed and novel manufactured nanomaterials (MNMs) and nano-enabled products with a lack of a coherent risk governance system to address their safety effectively. In response to this situation, a proactive system is needed to minimize the gap between the pace of innovation and the pace of developing nano-specific risk governance. With the Safe Innovation Approach (SIA), we seek to enhance the ability of all stakeholders to address the safety assessment of innovations in a robust yet agile manner. The SIA is an approach that combines a) the Safe-by-Design (SbD) concept, which recommends industry to integrate safety considerations as early as possible into the innovation process, and b) the Regulatory Preparedness (RP) concept which aims to improve anticipation of regulators in order that they can facilitate the development of adaptable (safety) regulation that can keep up with the pace of knowledge generation and innovation of MNMs and MNM-enabled products. SIA promotes a safe and responsible approach for industry when developing innovative products and materials, and stimulates a proactive attitude amongst policymakers and regulators to minimize the time gap between appearance and approval of innovation and appropriate legislation. Here we introduce a SIA framework consisting of creating SIA awareness, developing a SIA methodology (SbD scenarios, SbD methodology including information needs, functionality, and grouping, SIA Toolbox and a nano-specific database), bringing the Trusted Environment and RP concept into an operational level, and the development of novel business for industry and novel governance models for regulators. The SIA framework once implemented will result in a system for MNMs and nano-enabled products that is agile and robust. Current international efforts such as in the OECD are now trying to bring this concept to practice.