FLOW CHEMISTRY
Corning AFR G4 Reactor installation used in Angelini Pharma’ s trazodone HCl process
process became the first continuous manufacturing process started up at Aprilia site, marking a broader step in the company’ s flow chemistry.
The implementation also unfolded over several stages. Work on AFR G1 reactor trials began in late 2015. The first AFR G4 was ordered in early 2016, installed in late 2016 and brought into commercial operation in late 2017.
Angelini later ordered a second AFR G4 to increase product capacity, indicating that the process continued to deliver value at production scale over time. It also described the work as part of a broader platform covering R & D, pilot activities, scale-up and GMP production.
Key outcomes
The benefits were both technical and operational. One important gain was the ability to combine two chemical steps in a single reactor, helping to simplify the process by reducing the number of handling and transfer steps.
The continuous process also allowed operation under more controlled thermal and mixing conditions, with reactions carried out at around 90 ° C in an intensified environment. Just as importantly, process transfer from laboratory to industrial production became more straightforward through staged scale-up across the reactor family.
Angelini saw measurable reductions in the consumption of solvents( 30 %), 1-bromo-3-chloropropane( 50 %) and electricity( 23 %). The project also demonstrated a clear path to increased production capacity, first through scale-up to a single reactor and later through numbering-up with a second reactor, while still requiring lower plant volumes to reach the desired productivity.
The process was also addressed from a regulatory standpoint, with the pathway managed successfully in reference to both Italian Medicines Agency( AIFA) and US FDA requirements. That is significant because continuous manufacturing in pharmaceuticals also depends on a regulatory pathway that supports industrial implementation.
Implications for the sector
This example highlights a point that process teams already know well: flow chemistry is most useful when it is applied to a defined bottleneck. That may be a reaction limited by heat transfer or mixing, a process made difficult by intermediate isolation, or a process that works in the laboratory but becomes dangerous in production.
In each case, the value comes from solving a real problem. For that reason, continuous flow processes work best when they are evaluated as part of a broader manufacturing strategy, rather than as a direct substitute for batch.
The practical questions are more specific and determine whether a flow project moves beyond laboratory promise. Which steps genuinely benefit from lower hold-up volume or tighter thermal control? Where does removing an isolation stage simplify the process enough to matter? Which chemistries become easier to industrialise once the process is reorganised around continuous operation?
Corning AFRs have a role in that assessment as it supports process transfer across stages rather than at a single point in development. From early laboratory evaluation to pilot work and industrial manufacturing, the technology provides a framework for carrying suitable processes forward without completely redefining them at each scale, helping development and manufacturing teams work together.
Outlook
Flow chemistry’ s further adoption will continue to depend on where it offers a clear technical advantage. The strongest candidates will remain processes where batch introduces avoidable complexity, where reaction control is difficult or where the process can be materially improved by changing how it is executed.
Seen this way, the journey from lab to production is about timing as well as scale. When decisions are made early enough, flow chemistry can move from an interesting laboratory tool to a workable manufacturing platform. ●
*- Also contributing: Guillaume Gauron, manager at Corning and William Herbert Gazzo, R & D funding manager at Angelini Pharma
Corning Inc.
k + 1 607 442 2680 J reactors @ corning. com j www. corning. com / reactors
38 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981