The chemical sector contributes significantly to anthropogenic impacts on planetary health. Thus, there is a need for a green transformation. The same holds for the pharmaceutical sector. To assist with this transformation, European Commission's Joint Research Centre (JRC) developed a framework on Safe and Sustainable by Design (SSbD) for chemicals and materials (“SSbD framework”). The general structure of the SSbD framework leaves room for sector-specific priorities and practices. This study explores the applicability of the SSbD framework to the pharmaceutical sector; more specifically to the development, production and use of Human Medicinal Products (HMPs). We show that the stage-gate process in R&D of HMPs fits very well with the design-assessment process of the SSbD framework, making the framework conceptually applicable to pharmaceutical R&D. Future efforts should focus on the development of i) methods to predict environmental safety and sustainability based on the limited data available during R&D, ii) a pragmatic procedure integrating SSbD into HMPs innovation, and iii) a weighing system considering also environmental safety and sustainability parameters alongside patient safety and medical efficacy. Although the assessment phase of the JRC's SSbD framework has specifically been developed for innovation purposes, we propose an expansion of its scope to pharmaceutical products already on the market. The reason is its applicability by healthcare actors to guide safer and more sustainable choices regarding the use of marketed HMPs. We call this approach Safe and Sustainable by Comparison (SSbC) and show that the assessment principles of the SSbD framework can be applied to SSbC.