Fondaparinux Sodium Injection (ARIXTRA), originally developed by Aspen Pharma, was listed in the United States in 2002. It is used to prevent venous thromboembolism, which is prone to occur during orthopedic surgery of lower limbs, such as hip fracture, major knee surgery or hip replacement. In cooperation with West China School of Pharmacy, Sichuan University, the extreme difficult synthesis of Fondaparinux Sodium API was conquered by an 8-year development. In the preliminary study, through our novel synthetic route, the known complicated 70-step synthesis was reduced to 52 steps, and the linear step was reduced to 23 steps, which sets the solid foundation for industrialization. Our synthetic strategy, with fully independent intellectual property rights (CN201510591442.2), not only achieves great stereoselectivity and regioselectivity, but also avoids column purification in most steps.

Though two-year process research and development in large batch production in Sichuan Aupone Pharmaceutical R&D Center and production base, we have solved the problems of process stability, equipment compatibility, safety and environmental protection issues in large-scale production. To ensure the process stability and product quality, we have also accomplished the research on related impurities and quality control. In terms of quality, the purity of our API product is more than 99.7%, with single impurity less than 0.10% and the total impurity less than 0.3%, which is obviously better than the competitors’ and fully meets the requirements for quality consistency evaluation for injections. Besides, our API’s cost advantage is significant, due to well-designed synthetic strategy, purification optimization, and workshop lean management. In terms of production capacity, there are 3 GMP-standard workshops, with another 2 workshops under construction in our API production base. In the future, the annual output of Fondaparinux Sodium API is anticipated to be 50-100 kg/year. Thus, we are looking forward to establishing long-term strategic partnerships with customers globally.