Green Chemistry Challenge: 2024 Greener Synthetic Pathways Award

Merck & Co. Inc.

Merck & Co., Inc. is being recognized for developing a new “continuous process” for manufacturing its PD-1 therapy, KEYTRUDA® (pembrolizumab). Pembrolizumab is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Typically, these types of proteins are produced in large batches. Merck now uses a continuous process to produce pembrolizumab, in which the protein is filtered away from the cells continuously instead of performing a one-time filtration step at the end of a batch. This process can produce substantially more pembrolizumab per reactor volume, which allows Merck to use smaller equipment and thus shrinks the facility’s physical footprint, reducing the facility’s energy use. The continuous process also reduces the energy and water needed, as well as using consumables (such as filters) more efficiently. Reducing the amount of energy and water the facility uses prevents pollution by leading to fewer air emissions.

Summary of Technology

Merck & Co., Inc. is being recognized for developing a new synthesis for its PD-1 therapy, KEYTRUDA® (pembrolizumab). Pembrolizumab is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Typically, these types of proteins are produced in batches from cells that are engineered to produce the desired antibody. Cells are placed in a large vessel where they are allowed to grow for several weeks. The cells and other impurities are then filtered away, leaving the desired protein product. Merck now uses a “continuous process” to produce pembrolizumab, in which the protein is filtered away from the cells continuously instead of performing a one-time filtration step at the end of a batch. The continuous process can produce substantially more pembrolizumab per reactor volume, which allows Merck to use smaller equipment and thus shrinks the facility’s physical footprint. The smaller physical footprint of the facility helps prevent pollution because Merck is able to reduce energy consumption and therefore air emissions. 

Merck estimates this continuous manufacturing single-use process reduces energy consumption for Keytruda synthesis by about 4.5-fold; reduces water use by 4-fold; and reduces raw material usage by about 2-fold, thus reducing energy use and greenhouse gases for the facility.  

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