DIAGNOSTICS
Flow chemistry for on-demand production of essential bioreagents
Jean-François Vincent-Rocan of BioVectra discusses how continuous processing can enhance safety while minimising unit operations , increasing yield and speeding up reaction times
Pharmaceutical supply chains are susceptible to sudden changes in demand or disruptions in what is still largely a centralised manufacturing system . This was highlighted during the COVID-19 pandemic , when access to vaccines , medications and test kits was , at times , interrupted . 1 , 2
One example that occurred during the pandemic involved essential diagnostic tools used to identify pathogens . These testing kits rely on bioprocessing reagents that are commonly synthesised using decades-old procedures and technologies , making it difficult to produce material quickly , particularly when demand shifts unexpectedly .
Such was the case for 1,4-dithiothreitol ( DTT , also known as Cleland ’ s reagent ), a critical component in PCR testing kits . To address the limitations of the traditional synthesis , BioVectra has developed a synthetic process relying on flow chemistry that allows for a more efficient and safer protocol .
Additionally , with this intensified continuous flow synthesis , decagram quantities of DTT can be generated in less than 30 minutes from readily available raw materials . This improved process , which has so far proven successful at lab scale , has tremendous implications for the production of bioreagents and allows for a quicker response when the next unexpected event impacts demand .
Benefits of continuous flow
Conventional batch processing , while effective for making large amounts of medications , can lack the flexibility necessary to respond rapidly to sudden changes in demand . Continuous flow chemistry for drug substances could solve this issue by allowing local , on-demand manufacturing . It also has the potential to reduce drug development and manufacturing costs , simplify scale-up , enhance safety and improve process controls .
Sequestering hazardous intermediates within a continuous reaction diminishes the risk to chemists , while process improvements reduce the number of unit operations and reaction time . The apparatus ( such as a pressurised flow reactor ) allows for small-volume
Figure 1 - Published batch synthesis of DTT
reactions under lower temperatures and pressures than what is possible in batch chemistry , increasing the rate of reaction . It also reduces safety risks by preventing the release of hazardous vapours .
Scaling up a batch process means increasing the size of the reaction vessel , which alters the reaction conditions . In contrast , scaling out production with flow chemistry means running identical reactions under the same conditions , in parallel , thus reducing the challenges associated with scale-up .
Reducing the equipment footprint and speeding up synthesis allows more people in more regions to make essential bioreagents and APIs . This road could lead to pharmacy on demand , which uses continuous manufacturing to produce drug products while reducing the number of processing steps and time , all in equipment the size of a refrigerator . It has been used in proof-of-concept
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