Continuous flow chemistry

Leveraging our extensive expertise in pharmaceutical manufacture and complex and hazardous chemistry, we apply continuous flow chemistry in our customers’ API manufacturing programmes to help them unlock cost savings, mitigate risk, and improve process control.

Continuous flow chemistry has proven advantageous in the pharmaceutical industry for its ability to enable greater control over processing conditions, facilitating the safer handling of hazardous processes and reducing costs associated with API manufacturing. 

At Sterling, we have worked to develop our continuous flow chemistry capabilities for several years. Today, we are successfully running continuous processing projects in the lab through to multi-kilo scale.

Ready to discover how we can support your flow chemistry program? Speak to an expert. 

While there are many advantages to adopting flow chemistry in biopharmaceutical development and manufacturing, it also comes with several challenges. 

An experienced outsourced partner can help organisations overcome flow chemistry challenges including: 

• Regulatory considerations: Since the pharmaceutical industry has largely relied on batch manufacturing in the past, regulatory guidelines around continuous processing can be more challenging to interpret. At Sterling, we have 50+ years of GMP manufacturing expertise and a deep knowledge of global regulatory guidelines to ensure ongoing quality and compliance. 

• Infrastructure investment: Flow chemistry necessitates specialised equipment with specific cleaning procedures. With the appropriate flow reactors in place, we at Sterling help organisations get their flow chemistry projects up and running rapidly.

• Scale-up and downstream processing: Most available flow chemistry equipment is designed for the lab scale, requiring the team performing production to purpose-build GMP-ready flow equipment for scale-up. With full-lifecycle API manufacturing capabilities, we proactively plan for scale-up from day one while considering safety and engineering implications.
• Hazard evaluation: Flow chemistry can be useful for reactions involving hazardous reagents or intermediates, but handling such materials requires specialised expertise. We deliver years of experience in hazard evaluation to ensure any process we design will work safely and effectively on the plant. 

Flow chemistry’s applications in the pharmaceutical industry are widespread. Here are just a few examples of how we’re leveraging flow chemistry at Sterling today.

Harnessing flow chemistry to optimise THF waste treatment

Tetrahydrofuran (THF) is a useful solvent in many pharmaceutical processes, but can generate waste streams that contain epichlorohydrin, which must be neutralised. 

To remove the epichlorohydrin from waste, Sterling has worked to develop a flow chemistry process to bring the waste within specification for treatment and recovery. This process allowed for more efficient waste treatment, while freeing up batch reactors on-site. 

Read more about how we are harnessing flow chemistry to improve waste treatment.

Hydrogenation reactions in flow chemistry

Hydrogenation reactions are fundamental in pharmaceutical manufacturing, and are traditionally conducted in batch reactors. 

Sterling’s North Carolina site developed a continuous flow chemistry process for hydrogenation reactions that circumvents some of the challenges associated with large-scale hydrogenolysis reactions. 

The new process allows for the use of higher pressures and temperatures while ensuring greater control and mitigating safety risks. 

Read more about hydrogenation reactions in flow chemistry.

At Sterling, our expertise and track record in route selection and development of industrial processes enables us to knowledgably select the most appropriate reactor solutions to meet our customers’ requirements in their flow chemistry programs. 

We provide expert advice on appropriate route design, along with guidance to ensure safety and compliance throughout each stage of the manufacturing process.

Following are some of the things that contribute to our strength in continuous processing:  

• Expert partners: Our work in continuous processing is supported by our Technology and Innovation Programme, which focuses on developing partnerships with industry and academia to bring the latest innovations and technologies to our customers’ projects.
• Specialty in hazardous chemistry: The flow chemistry solutions we deliver are a natural complement to our range of expertise and proven track record in pharmaceutical synthesis and hazardous chemistry.
• Robust solutions: We utilise various flow-based reactors, which by design contain only a small amount of reactive material in the reactor at a given time. This enables us to deliver robust continuous processing solutions, increasing flexibility in manufacture whilst improving safety and reducing waste.
• Ongoing development: We have successfully handled continuous processing for a range of development projects at the lab scale, and we are actively expanding our capabilities to support continuous processing at the multi-kilogram and larger manufacturing scales.

Our work in continuous processing builds upon an established track record of handling the most complex and hazardous chemistries, supported by a proven hazard evaluation approach. 

Continuous processing enables us to expand our processing capabilities and further improve the safety and stability with which we handle hazardous processes and compounds.

Continuous flow chemistry is a chemical process where reactions are performed in a continuous stream, as opposed to in batch reactors. 

In addition to its rising prevalence in biopharma development and manufacturing, flow chemistry is widely used in food and beverage, fine chemicals, petrochemicals, and other industries.

Flow chemistry delivers several compelling advantages in biopharmaceutical development and manufacturing, including:  

• Risk mitigation: With less exposure to extreme conditions, flow chemistry enables greater control over hazardous and unstable intermediates.

• Enhanced efficiency: Continuous flow chemistry enables 24/7 operations and eliminates the need to clean down equipment between batches. It also gives added advantages with respect to changing demand based upon manufacturing time rather than batch sizes.

• Cost-effectiveness: Process intensification leads to reduced processing time, higher throughput, and more efficient resource utilisation, making flow chemistry a powerful opportunity for cost savings.
• Waste reduction: The use of flow reactors eliminates the need to waste large batches of unusable material in the event that anything goes wrong.

Flow chemistry has widespread utility across different stages of development and types of synthesis. Some key applications include: 

• Early stage discovery: Flow chemistry can accelerate discovery by enabling rapid synthesis of compound libraries for streamlined hit-to-lead optimisation.
• API synthesis and manufacturing: Continuous flow chemistry is particularly useful in the manufacture of toxic or potent compounds, such as high-potency APIs, as it helps to minimise exposure to these hazardous compounds.
• Peptide synthesis: Flow chemistry can be utilised to enable more precise control and save time in both solid-phase and liquid-phase peptide synthesis.
• Drug conjugates: Continuous flow chemistry can be leveraged for linker synthesis and conjugation in advanced therapeutics such as antibody-drug conjugates.  

While there are many advantages to adopting flow chemistry in biopharmaceutical development and manufacturing, it also comes with several challenges. 

An experienced outsourced partner can help organisations overcome flow chemistry challenges including: 

• Regulatory considerations: Since the pharmaceutical industry has largely relied on batch manufacturing in the past, regulatory guidelines around continuous processing can be more challenging to interpret. At Sterling, we have 50+ years of GMP manufacturing expertise and a deep knowledge of global regulatory guidelines to ensure ongoing quality and compliance. 

• Infrastructure investment: Flow chemistry necessitates specialised equipment with specific cleaning procedures. With the appropriate flow reactors in place, we at Sterling help organisations get their flow chemistry projects up and running rapidly.

• Scale-up and downstream processing: Most available flow chemistry equipment is designed for the lab scale, requiring the team performing production to purpose-build GMP-ready flow equipment for scale-up. With full-lifecycle API manufacturing capabilities, we proactively plan for scale-up from day one while considering safety and engineering implications.
• Hazard evaluation: Flow chemistry can be useful for reactions involving hazardous reagents or intermediates, but handling such materials requires specialised expertise. We deliver years of experience in hazard evaluation to ensure any process we design will work safely and effectively on the plant.