Asymchem Takes New Step on Application of Continuous Reaction

This scheme represents typical operations comprising many integrated flow processes.

Asymchem has become a global leader in the pharmaceutical CDMO industry. Asymchem has been committed to the development and commercial application of green pharmaceutical technologies for many years.

The pharmaceutical industry is now facing new challenges in controlling and preventing environmental pollution as it is expanding. “Greening” of pharmaceutical processes is adopted as a goal by many national governments; “green chemistry” is vigorously integrated to the business strategies of many pharmaceutical companies. Green chemistry represented by continuous reactions and bio-enzyme catalysis is expected to be an efficient way to increase production efficiency and reduce waste generation, energy use, and production cost. 

The batch production is usually adopted for traditional drug synthesis, in which large amount of solvents is used, with problems of low yield, high energy consumption, and serious pollution. As a new alternative route, continuous reaction has been applied through which materials being processed are continuously in motion in the whole production process, undergoing chemical reactions or subject to mechanical or heat treatment; online monitoring appliance is also used to monitor and evaluate the probability or impact of risks to avoid accidence. Converting the traditional batch operation to continuous operation has many advantages including, but not limited to higher safety, environmental protection, more throughput in shorter time at less cost, and accelerated drug launch.

Through continued R&D investment over the past 20 years, Asymchem has successfully applied the continuous reactions to commercial production of the key intermediates and APIs of the third line penem antibiotics, second line anti-HIV drugs, anti-cancer drugs and other innovative drugs. The successful application of continuous reaction has become a powerful tool to realize the large scale production in the pharmaceutical industry.

4-AA is a critical starting material for the synthesis of penem antibiotics and is in high demand. Ozone, commonly used as oxidant in traditional production process, is highly risky and the temperature and homogeneity of product is hard to precisely control. The process of continuous ozonolysish reaction developed by Asymchem is safer and more environmentally friendly. The fluids and ozone can be continuously injected to the device; waste gas and products can be continuously discharged from the device; online monitoring and PLC auto-control system is applied with multiple interlock to ensure safety. The output of one set of equipment alone can produce 40mt/year. The equipment has many prominent advantages including full automatic control, space saving, higher degree of safety, shorter life cycle, high yield and purity, less cost and energy use, green.

Moreover, Asymchem developed a new synthetic route for commercial EP production– only 3 steps is needed the shortest route of synthesis. The EP flow chemistry equipment for commercial production has completed the test and will be verified soon. The equipment is equipped with continuous immobilization reaction column and PFR, used respectively for continuous cyclization reaction and continuous esterification reaction. The set of equipment uses HPLC to monitor the drug quality and DCS system to achieve precise automatic control. The equipment has advantages of space saving, high productivity of >60mt/year/one set, less catalyst and easy recycle. The large scale production of EP was realized through combination of blocks and automatic control, an example of End-to-End green production.

Asymchem has received many awards and qualifications for the company’s contribution in the R&D and application of continuous reaction technology. Asymchem was awarded with “the Excellent Award for Chinese Patented Invention”, “Special Award for Green Pharmaceutical Technology in 2017/2018” and others. Asymchem was recognized as “State-certified Enterprise Technology Center”, “National and Local Green Chemistry Collaboration Laboratory”, “Tianjin Municipal Enterprise Key Laboratories of Green Synthetic Technology”, as well as a member of “ACS GCI Green Chemistry Roundtable”. Moreover, Asymchem has also established the International Green Chemistry Collaboration Laboratory with Professor K. Barry Sharpless, Nobel Prize winner in Chemistry, Prof. Jin-Quan Yu, MacArthur Genius Award winner, and Prof. Phil Baran, MacArthur Genius Award winner from Scripps Research Institute, with an aim to promote the green pharmaceutical technology to the production of innovative drugs and blockbuster drugs in major therapeutic areas.

Asymchem will continue to invest resource and committed efforts to develop green pharmaceutical technologies. The philosophy of “Green Chemistry Is the Future” is at the forefront of everything Asymchem does in its mission to promote the innovation and aid in the progress of the global pharmaceutical industry.