From Bottleneck to Breakthrough: Developing a Sustainable and Scalable Manufacturing Process for a Complex ADC Drug-Linker

The Merck team, consisting of Patrick Fier, Patrick Moon, Scott McCann, Tao Liang, Greg Estrada, Marc Poirier, Reed Larson, Lu Wang, Gao Shang, and Fuh-Rong Tsay, received this award for their work, “From Bottleneck to Breakthrough: Developing a Sustainable and Scalable Manufacturing Process for a Complex ADC Drug-Linker”. They demonstrated the impact of applying green chemistry principles in the manufacturing process of the linker for the antibody-drug conjugate (ADC) Sacituzumab tirumotecan (MK-2870). Originally, the manufacturing process had long lead times due to the 20-step synthetic sequence and faced a major bottleneck with the final purification that limited production to less than 100 g per month even with 24/7 operation in a high-potency chromatography suite. Major improvements were achieved by developing a synthesis from a widely available natural product that cut seven potent steps down to three. The Process Mass Intensity (PMI) was reduced by approximately 75%, and the amount of energy-intensive chromatography time was decreased by >99% compared to the original route. This work highlights the advantages of investing in greener and more sustainable processes that naturally improve the global supply of medicines to patients.