Our most recent update from Group Leader Andrew Jordan sharing his thoughts on recent developments in PR&D.
Recently, I attended the 39th SCI Process Development Symposium at Churchill College, Cambridge, with my colleague Paul Shaw. Over the 3-day event, highlights of some of the best process chemistry innovation, advances, and problem solving were presented by leaders in the field.
The real highlight for me was that several more “esoteric” methodologies such as flow-, electro- and enzymatic- chemistry are now becoming mainstream and that by embracing these technologies, you give yourself more options for successful project delivery. Sustainability was also a central theme that ran throughout many of the presentations. Waste costs money and generating more waste than necessary means that there is an inefficiency in your process. Perhaps process chemists are the original “Green Chemists”?
Something that really caught my attention was the drive to utilise biocatalysis in large-scale synthesis. For example, work presented by Shane Mckenna from Bristol Myers Squibb really demonstrated the power of enzymatic synthesis; a two-enzyme cascade was employed for the >100 kg preparation of a prohibitively expensive chiral building block, reducing project costs by 82% and waste generation by 86%! It looks like enzymatic synthesis is here to stay and can, when utilised in specific transformation types, add immense value.
The ground-breaking synthesis of Pfizer’s Nirmatrelvir a.k.a. Paxlovid was also presented. The two 40-minute presentations from Chris Allais and David Daniels really did justice to this PR&D tour-de-force; the API development was accelerated at “light-speed”, going from the first 7 mg in July 2020, to a x5000 fold increase in production by Dec 2021. Such rapid development in API manufacture is unheard of and relied on a combination of mass deployment of resources and a close working relationship with regulators. Normally this type of process would take 9 years, not 9 months.
Finally, the use of flow chemistry to continuously manufacture API intermediates really caught my eye. Previously considered more of an academic curiosity, flow chemistry has come on leaps and bounds in the past 5-10 years. Heena Panchal from AstraZeneca demonstrated elegantly that flow chemistry can be a valuable and impactful tool. The team at AZ transferred a single step of a manufacturing sequence from batch to flow conditions, increased yield by 20%, dramatically improved the purity profile, increased throughput by 100%, and reduced plant time by 15 days! The waste reduction was also phenomenal, calculated to be at least 700 million liters of water and 350 tonnes CO2. The process was run on 400 kg scale and was scaled directly using 1 L glassware.
Having seen the recent developments in the PR&D field at the 39th SCI Symposium, I can confidently say that Charnwood Discovery are well equipped to meet present and future PR&D needs, having made recent investments in DoE, flow-, photo- and electro-chemistry to aid all aspects of route development.
Find out about our process research and development capabilities here.
Andrew Jordan
Group Leader, Chemical Development
