Cheaper synthesis route for COVID-19 drug: A collaboration with M4ALL
Molnupiravir (MK-4482, EIDD-2801) is an experimental drug that has been demonstrated to be effective for the treatment of COVID-19 in human clinical trials. The M4ALL, a non-profit organization, is working on a low-cost, two-step process to allow the production of Molnupiravir, with the aim of having affordable medicine for everyone. In this insight, we will discuss on this cheaper synthesis route for COVID-19 drug and the contribution of the Rotating Bed Reactor (RBR).
Medicines for All Institute (M4ALL) is located at Richmond, Virginia dedicated to reducing the cost of producing high-quality medications so that they are available to everyone. The M4ALL platform enables the manufacturing of active pharmaceutical ingredients (APIs) and enhances the safety of the supply chain of medicines around the world by optimizing API production. Bill & Melinda Gates Foundation funded M4ALL in 2017.
The unique approach of M4ALL combines novel chemistry with the fundamental elements of process intensification. These elements include:
- An integrated approach to developing advanced starting materials based on commodity chemicals
- Using a minimum of unit operations with common solvents and limiting intermediate isolation to combine high-yielding reactions.
- Evaluation of alternative manufacturing platforms.
Work done by M4All
M4ALL recently published an article on low-cost, two-step process developed a new enzyme, cytidine aminotransferase, to allow the production of Molnupiravir intermediate as a COVID treatment drug, with the aim of having affordable medicine for everyone. This article is titled "Molnupiravir: Enzyme Recycling Information for M4ALL’s Two-Step Enzymatic Process". This M4ALL project aimed to reduce costs and cut waste with the use of Rotating Bed Reactor (RBR). Read the article here.
Enzyme Recycling Lowered the Overall Raw Material Cost in M4ALL’s Enzymatic Route to Molnupiravir
M4ALL recently disclosed a low-cost, two-step process to molnupiravir starting from cytidine with the following properties:
- The total raw material costs for this process was estimated to be $260/kg
- A significant cost driver was the polymer-supported lipase enzyme Novozyme 435 (50% of the total raw material cost)
To further lower raw material costs, the critical process parameters that were necessary to recycle the enzyme were identified, and an Rotating Bed Reactor (RBR) was used.
Use of RBR
RBR is an innovative technology designed by SpinChem, Sweden. This technology was explored to mitigate cost and waste issues in production of Molnupiravir. With the RBR, it was possible to have stir rates of up to 1000 rpm without significant physical degradation of the catalyst.
Before using RBR, the total raw material cost for this process was estimated to be $260/kg. With the use of RBR, the total raw material cost could potentially be reduced to $160/kg, assuming three reuses of the enzyme.This helped in reducing the cost of production and cutting waste by 38%, thus contributing towards enabling affordable medicines.
It was possible to reduce the mechanical breakdown of the catalyst caused by a conventional stir blade with RBR.
Enzyme Recycling Experiments: Key Findings
Extremely slow stirring speeds was required to avoid mechanical decomposition of the supported enzyme by the stir blade. By using the RBR a solution to this issue was provided. Stirring rates of up to 1000 rpm were tested without significant degradation of the catalyst.
With the use of RBR, the total raw material cost could potentially be reduced to $160/kg, assuming three reuses of the enzyme. reducing overall cost of production and cutting waste by 38%
Thus, use of RBR proved beneficial here.
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2022-03- 15 06:30