Industry Insights with… Samuel Bourne
Welcome to the latest blog in our Industry Insights series, where we ask our experts to share their extensive expertise on topics within the pharmaceutical industry. We recently asked our Process Development Chemist and in-house flow chemistry expert, Samuel Bourne, to discuss the advantages of continuous flow for API manufacture.
Flow chemistry is a technique that has been used in the fine chemicals and petrochemicals industries for many decades. The pharmaceutical industry is now embracing continuous flow technology for the efficient synthesis of APIs. Samuel’s insights provide an overview of flow chemistry and explains the benefits of incorporating flow reactors for drug substance development.
Please can you provide an overview of continuous flow and the advantages of its use in the pharmaceutical industry.
Flow chemistry is a smarter way of manufacturing complex molecules. The technology offers many advantages over traditional batch methodology for the development and manufacture of APIs, including greater control of process parameters and online analytics. Flow chemistry enables accelerated process optimisation and scale-up, resulting in a compressed drug development life cycle. Moreover, the employment of flow technologies is providing a cleaner and more efficient way to produce pharmaceuticals.
How does continuous flow differ from a batch approach?
Traditional batch processes are performed in large tank reactors whereas flow processes involve running chemical reactions in a continuously flowing stream. While batch methodology has proven to be a simple and effective way of containing and running reactions, a flow process can produce the same quantity of material using a reactor only a fraction of the size. This is possible as flow systems are able to process many times their volume in a continuous, uninterrupted fashion. Continuous flow provides a major advantage in terms of process safety as inventories of reactive or hazardous intermediates can be kept to a minimum.
Which types of chemistry are particularly suited to flow?
There are several classes of reaction that benefit significantly from continuous flow. These include fast reactions such as lithiation-borylation chemistry. Reactions that require cryogenic conditions can be more precisely controlled using a flow reactor. Risks associated with highly hazardous or potentially explosive chemistries can also be mitigated due to the smaller reactor volume. High temperature thermal rearrangements can be performed in super-heated solvents, expanding the list of solvents and conditions available to flow chemists. In addition, we are seeing a resurgence in photo- and electro-chemistry thanks to innovations in flow reactor design.
What factors should be considered when choosing between flow and batch?
Flow chemistry is not the answer to everything – the suitability of a process to batch or flow methodology should always be considered on a case-by-case basis. The key determining factors are the reaction time and the solubility of reagents and products. In terms of throughput, the choice will also depend on the assets available and the space-time yield of a specific process in those assets.
What are Arcinova's capabilities in these two areas?
At Arcinova, our investment in modular continuous flow technologies, alongside state-of-the-art batch reactors, provides our customers with the greatest degree of flexibility and capability for their processes. Many companies have heavily invested in batch technology and have a limited capacity to add new capabilities in flow manufacturing. Arcinova can develop flow processes by first intent, which allows us to optimise and scale-up quickly while delivering larger quantities of drug substance efficiently and cost effectively.
Which technological advances in continuous flow manufacturing are set to revolutionise the industry?
At the moment there is a huge drive towards full process automation with a lot of work going into the computational side of predictive process control. Machine learning and AI will start to provide powerful tools for process optimisation and control. These tools go hand-in-hand with the development of new types of flow reactors for handling more exotic chemistries. All these technological advances will certainly widen the chemical space in which we operate and will hopefully lead to new discoveries in the field of organic chemistry.
If you would like to learn more about flow chemistry and the work of our Drug Substance development team, please get in touch here: https://arcinova.com/contact-us