Continuous manufacturing for supply chain security
Dr Charlotte Wiles , CEO of Chemtrix , and Dr Eric De Vos , VP of global innovation and R & D director EU at Ajinomoto Bio-Pharma Services , share their collaboration on a project in the area of continuous manufacturing
Global events continue to highlight the risks associated with the reliance on global chemical supply chains and an increasing number of countries are now actively ‘ bringing back ’ the manufacture of critical raw materials , intermediates and products . This comes with challenges after decades of outsourcing , with local production infrastructure often unavailable , or needing to be reestablished or expanded . As a result , small modular continuous flow plants are gaining attention as an appropriate solution to secure these local supply chains while ensuring safe , sustainable processes are implemented . With the uptake of continuous manufacturing growing in the fine , speciality and pharma sectors , the number of projects that are actively scaling up from proof of concept towards manufacturing continues to increase . Collaboration has been a key factor in realising this growth and can take many forms , ranging from crossdepartmental activities to external collaboration with service providers , hardware suppliers and regulators through to working groups with industry peers . In this article , Chemtrix and Ajinomoto Bio-Pharma Services present their collaboration on a project in the area of flow chemistry that took a diazomethane process from batch into continuous flow at a scale of 500 tonnes / year , facilitating the supply of a specific cyclopropanated product for which demand was growing .
Why ‘ go with the flow ’?
Important process advantages arise when you reduce the size of
Lab-scale flow process development in Protrix , enabled by FTIR PAT
a reactor . Mixing can be achieved in the milliseconds to seconds range and a high surface-to-volume ratio ( typically thousands of times larger than batch ) enables rapid heating or cooling of the reaction mixture , resulting in safer operation of exothermic processes and the formation of cleaner products . Reaction temperatures above a solvent ’ s atmospheric boiling point are routinely used to intensify processes , leading to shorter reaction times , increased product selectivity and high unit productivity . When optimising a process , the small hold-up volume in a flow reactor is advantageous as it allows rapid parameter screening in terms of time , temperature , concentration , stoichiometry and pressure , while using small quantities of material . For production , a small hold-up volume enhances process safety , as only a small quantity of reactive or unstable intermediate is present at any one time and leaving the process running 24 / 7 delivers the required quantity of material .
For close to two decades , the US FDA and other regulatory bodies have encouraged the adoption of emerging technologies that aim to ensure high quality materials for patients and to mitigate against drug shortages . 1 The release of ICH Q13 ‘ Continuous Manufacturing for Drug Substances and Drug Products ’ is anticipated within the year .
Continuous growth
In recent years we have seen the reasons for a company to change from batch to flow vary , depending on the sector , process type of interest and scale of operation . Supply chain security and improvements in process sustainability are strongly emerging drivers for the wider adoption of continuous manufacturing .
The ease of unit replication ( scaleout ) enables multiple identical set-ups to be deployed , providing either an onsite increase in output or on-demand production in different locations , as a means of securing supply chains . With the product requirements at the centre of any process development ,
42 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981