Both, the Green Chemistry principles as well as the Safe and Sustainable by Design (SSbD) framework consider biodegradability as a crucial property of chemicals and promote design for degradation to reduce their environmental impact. The development of active ingredients for application in human and animal health as well as crop protection already comprises the investigation of multiple environmental safety parameters including persistence. However, existing methods to assess environmental biodegradability are often time-consuming, costly, and focus on a single development candidate. In addition, their limited throughput renders them impractical for use in the drug discovery (i.e., research) process to inform API design and optimization towards better degradability. Therefore, the ACS GCI Pharmaceutical Roundtable’s focus team on API Biodegradation strives to develop practical workflows and tools to measure and predict API biodegradation or persistence and build a structural understanding of biodegradability to allow optimization of the property prior to preclinical candidate selection.