Green Chemistry Challenge: 2019 Greener Synthetic Pathways Award
Merck & Co.
Innovating for a Greener Future: Development of a Green & Sustainable Manufacturing Process for ZerbaxaTM
Merck Research Laboratories is being recognized for redesigning the manufacturing of the antibiotic ZerbaxaTM. Key to the redesign is a crystallization-based purification process that reduces the process mass index by 75%, reduces raw material costs by 50%, and increases the overall yield by more than 50%. Merck estimates that the new process will save approximately 3.7 million gallons of water annually and reduce the carbon footprint and energy usage by 50% and 38%, respectively.
Summary of Technology:
Ceftolozane sulfate is the cephalosporin antibiotic component of ZerbaxaTM used to treat gram-negative bacterial infections that have become resistant to conventional antibiotics, especially urinary tract and intra-abdominal infections. The existing manufacturing process for ceftolozane sulfate was comprised of three stages and included the use of hazardous chemicals, an unacceptably high process mass index, long cycle times, and low yields.
Merck achieved innovations in both synthetic chemistry and process development leading to a truly sustainable second generation (Gen 2) manufacturing route to ceftolozane sulfate. Key to the development of a sustainable process was crystallization-based purification, the invention of which dispelled the traditional belief that chromatography was the only method capable of purifying β-lactam antibiotics.
This discovery of the sustainable crystallization-based purification process led to a revolutionary new process that reduces the process mass index by 75%, reduces raw material costs by 50%, and increases the overall yield by more than 50%. Merck estimates that the new process will save approximately 3.7 million gallons of water annually, which equals enough drinking water for approximately 21,000 people per year. In addition, life-cycle assessment data shows that the new process is expected to reduce environmental impact by decreasing the carbon footprint and energy usage by 50% and 38%, respectively.
This patented process was successfully implemented, demonstrated, filed, and approved in the US and EU in 2018, and is currently being used on commercial scale to manufacture ceftolozane sulfate for ZerbaxaTM.