Harnessing flow chemistry in API manufacturing
Flow chemistry has been used in industry for more than 100 years, most commonly in the manufacture of bulk chemicals.1 Compared to batch manufacturing, continuous processing delivers compelling advantages like enhanced efficiency, safety and control. As a complimentary technology to traditional batch manufacturing that has the ability to handle certain chemistries that are challenging in batch, flow chemistry is a promising solution for the pharmaceutical industry.
Today, more and more pharmaceutical and biotechnology organisations are embracing continuous manufacturing for its many advantages, but this effort is not without its challenges. An experienced partner can help to address these considerations in order to unlock the full potential of flow chemistry.
The global flow chemistry market is anticipated to grow at an
11.2% CAGR through 2030.2
In numerous examples, flow chemistry has been utilised to achieve
How it works
Unlike start and stop batch manufacturing, flow chemistry reactions continuously occur in a reactor. Click each part of the diagram below to learn more.3
Small volumes of reactants enter the reactor at a time and the reaction occurs. A catalyst may also be flowed through or contained in the reactor to accelerate processes.4
Reactants are generally flowed into the reactor on a continuous basis. Because the reactor enables enhanced control, hazardous or highly reactive reagents can be utilised safely.4
Barriers to adoption for the pharma industry, and how the right partner can help
While flow chemistry’s potential is powerful, its challenges are also prevalent. Click each box below to discover how the right partner can help you address some of the most common obstacles associated with embracing flow chemistry.
Given that flow chemistry is relatively new to the industry, regulatory requirements can be unclear. Regulatory agencies do not specify strict procedures. Instead, they provide guidelines for best practices.5
A partner that has extensive expertise working with customers in different parts of the world will deliver a deep familiarity of the regulatory landscape to ensure quality and compliance.
Infrastructure and cost
Flow equipment must be carefully cleaned between each project,5 and it can be time consuming to train team members on how to properly handle the equipment. Equipment costs can quickly add up.
Infrastructure and cost
Organisations can save time and resources by working with an outsourced partner who already has the specialised equipment and experienced team members necessary to handle continuous manufacturing. This eliminates the cost of implementing flow equipment internally.
Flow chemistry can be utilised for various chemical processes, including hazardous chemistry and extreme conditions. The right partner can help to identify where it provides the most utility.
An experienced partner can deliver guidance around where flow chemistry may deliver the greatest benefit. They will closely collaborate with customers to optimise processes and advise on best practices.
Because it is more contained and requires smaller volumes of material, flow chemistry can be preferable to batch manufacturing when handling hazardous compounds.4 However, comprehensive hazard evaluation is still necessary to protect the people and product.
A partner that couples robust hazard evaluation capabilities and experience with flow chemistry expertise will ensure that hazardous materials are safely handled in flow.
Realising the potential
Once you select the right partner, you can begin to realise the full potential of continuous manufacturing. Following are some of flow chemistry’s key benefits for pharmaceutical and biotechnology organisations like yours.
Flow chemistry enables improved heat and mass transfer due to the smaller size of reactors. In addition, only a small amount of material is lost in the event of a failure, as opposed to an entire batch.
With smaller reactors and more efficient heat and mass transfer, can deliver significant efficiency gains.4
As opposed to batch manufacturing, flow chemistry enables the safer handling of hazardous intermediates. The smaller volumes utilised at a time in continuous manufacturing limit the operator’s exposure to hazardous material5 and minimise the amount of energy that could potentially be released in a safety event.6
Flow chemistry has been successfully used for reactions involving nitration, azides, cyanides, diazonium compounds and more.6
In addition to enhanced efficiency, flow chemistry can also enable higher yields than batch manufacturing.1 When coupled with the reactor’s ability to run 24/7 without added labour to start and stop operations, continuous manufacturing can create an opportunity for cost savings.
Flow chemistry has the potential to reduce manufacturing costs by up to 40%.7
Once steady state is achieved, continuous reactors can enable greater consistency by manufacturing product to the same quality and yield. It also supports a high level of control over key reaction components.8
Flow chemistry can improve monitoring of reaction parameters like reactant quantity, mixture, temperature, time and solvent amount.1
Partnering to maximise flow chemistry success
At Sterling, our dedicated Centre of Excellence in Continuous Chemistry supports our research into commercial applications of this technology. With expert team members and a commitment to innovation, we are focused on continually expanding our flow chemistry services to empower our customers. All of this is supported by our dedication to serving as true scientific partners, taking the time to fully understand our customers’ needs to help them realise the full potential of their project.
Are you ready to discover how flow chemistry can transform your programme?
- Burange, A.; Osman, S.; Luque, R. Understanding flow chemistry for the production of active pharmaceutical ingredients. iScience [Online] March 18, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867129/ (accessed May 31, 2022).
- Grand View Research. https://www.grandviewresearch.com/industry-analysis/flow-chemistry-market (accessed May 26, 2022)
- Flow chemistry technology. Future Chemistry. https://futurechemistry.com/flow-chemistry-technology/ (accessed May 31, 2022).
- Porta, R.; Benaglia, M.; Puglisi, A. Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products. Org. Process Rev. Dev. [Online] November 26, 2022. https://pubs.acs.org/doi/10.1021/acs.oprd.5b00325 (accessed May 31, 2022).
- Continuous processing: the future of pharmaceutical manufacturing. Manufacturing Chemist, April 27, 2018. https://www.manufacturingchemist.com/news/article_page/Continuous_processing_the_future_of_pharmaceutical_manufacturing/142250 (accessed May 26, 2022).
- Gutmann, B. and Kappe, C. Continuous flow processing in the pharma industry—an unstoppable trend? European Pharmaceutical Review [Online] October 22, 2015. https://www.europeanpharmaceuticalreview.com/article/35936/continuous-flow-processing-in-the-pharma-industry-an-unstoppable-trend/ (accessed May 31, 2022).
- Hartman, R. Flow chemistry remains an opportunity for chemists and chemical engineers. Current Opinion in Chemical Engineering [Online] September 2020. ScienceDirect. https://www.sciencedirect.com/science/article/pii/S2211339820300290 (accessed May 31, 2022).
- Hone, C.; Kappe, C, O. Towards the Standardization of Flow chemistry Protocols for Organic Reactions. Chemistry Methods [Online] September 2021. Chemistry Europe. https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cmtd.202100059 (accessed October 11, 2022).