Active pharmaceutical ingredients (APIs), their metabolites and transformation products (TPs) occur in the environment around the world. They endanger the environment and human health. These alarming circumstances highlight the urgent need for effective action, which is also reflected in EU strategies on sustainable chemicals and pharmaceuticals in the environment. The design of active ingredients that mineralize in the environment according to the Benign by Design (BbD) concept is a promising approach to meet this challenge. However, their implementation in the industrial API discovery process has not yet been discussed. To stimulate such discussion and better understand the applicability and limitations of this approach, the generic API discovery process will be reviewed, including procedures, principles, and paradigms based on publicly available information. In addition to the concept of BbD itself, workflow scenarios such as de novo design and re-design are presented in order to enable a better understanding of the feasibility. If we bring both aspects together, we come to the conclusion that the optimization phase within drug discovery seems to be the most suitable point to implement environmental aspects. At this early stage, the cost is low and the potential impact of design and variations in structure on the outcome is high. We have found that the pharmacological parameters required for its application sometimes even correspond to the biodegradability in the environment, since the conditions in the human body and in the environment are different. However, the effects on the biodegradability of active ingredients in the environment by optimizing pharmacological parameters such as toxicity and stability must be taken into account along with design rules for biodegradability. Understanding the feasibility of BbD can mitigate the concerns expressed by stakeholders and encourage them to invest in research and development, as well as help pharmaceutical companies prepare for upcoming regulations as the above-mentioned EU strategies herald further policy regulations. We have also found that the successful implementation of BbD depends on the availability of suitable tools and methods as well as incentives for research and development in constructive cooperation between industry, science and authorities.


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