Green Chemistry and Engineering

Safe and Sustainable by Design

Safe and Sustainable by Design (SSbD) is a new framework for assessing the development of new chemicals and the design of products (Apel et al., 2024). It encourages process and product designers and manufacturers to introduce elements of Green Chemistry and Green Engineering, preemptive risk assessment (hazard avoidance), and life cycle assessment early in the development stages. Product and process design should meet sustainability objectives by significantly minimising environmental footprint of the whole ‘system’ in a wider sense, which is achieved by taking a complete life cycle perspective (Caldeira et al., 2022; EC, 2020).  

As such, SSbD aims to avoid a lack of safety and sustainability at the start-of-pipe (i.e. the design phase of a system) by adequately addressing safety and sustainability at the earliest opportunity and embedding this into the design. This is considered more effective than trying to find solutions for a lot of problems at the end-of-pipe (i.e. minimising the adverse effects of the chemicals you have produced, rather than avoiding them in the first place). The holistic design approach of SSbD addresses the complexity and variety of safety and sustainability parameters through whole systems thinking (Mahaffy et al., 2019), from production to eventual fate in the environment to avoid rebound effects and to identify and minimise trade-offs with other safety and sustainability aspects where possible. For example, there may be a trade-off between low energy costs (e.g. stable pharmaceutical products will not require an energy-intensive cold chain) and impact on ecosystems at end-of-life (e.g. stable pharmaceutical products may persist in the environment).  

SSbD is structured as a generic stage-gate process, meaning it is not specific to pharmaceuticals. Within each stage, a (re)design phase and an assessment phase are iteratively performed. This results in a go/no-go decision being made on reaching the next stage. Design principles for safety and sustainability are proposed during the (re)design phase as early as possible. There is overlap with the Benign by Design concept as it is a building block of SSbD. In total, 8 design principles have been proposed (see below) (EC, 2022).

The safety and sustainability assessment consists of 5 sections, each one expanding in scope (Caldeira et al., 2022). Firstly the inherent hazards of the chemicals being used are assessed. These can be ranked and alternatives sought where available. The second step considers the exposure to chemical substances in the production phase. The risk to workers is a function of hazard and exposure. This covers:

• Physical hazards such as flammable or explosive substances;

• Chemical hazards such as toxicity or allergic reaction;

• Environmental hazards are also considered, e.g. ecotoxocity, ozone depletion.

Step 3 expands the safety assessment to consumers and the environment. Exposure is calculated based on the type of product and the quantities of any hazardous substances within. For pharmaceuticals, the intended use of the product inevitably results in high human exposure and so the inherent hazards of the API and excipients must be minimised. Factors determining the fate of pharmaceuticals in the environment are covered later. Step 4 is life cycle assessment, also covered in a subsequent section, which introduces environmental sustainability into the assessment. Step 5 considers social and economic sustainability but there is much work still to be done in defining appropriate and robust indicators. As such, the guidance for step 5 is currently limited.

The assessment process depends strongly on the availability of information about the system. As the product/process design evolves and matures, more information becomes available (Caldeira et al., 2022). This requires a screening cascade with increasing complexity for safety and sustainability parameters next to function related parameters. Screening methods and tools on safety and sustainability parameters are currently under further development. Prediction tools play a very crucial role for an early screening. 

For pharmaceuticals, there are multiple function related properties that are interconnected with properties regarding the fate and effects of the pharmaceutical in the environment. This demonstrates the importance of considering the various parameters simultaneously. All properties need to be balanced (Puhlmann et al., 2024).