From molecule to API: Faster and controlled scaling up with flexible reactor technology

Hastelloy(r) cover plate of glass lined HPAPI reactor system | Photo: Büchi AG

FlexyCUBE for parallel synthesis | Photo: Systag System Technik AG

Kiloclave pressure reactor | Photo: Büchi AG

ChemReactor | Photo: Büchi AG

Process equipment | Photo: Büchi AG

Glass valves for HPAPI process equipment | Photo: Büchi AG

Developing and manufacturing Active Pharmaceutical Ingredients (APIs) faster, more efficiently, and in a controlled manner requires a modern, agile approach. Traditionally, process development and manufacturing are separated by rigid systems, but the pharmaceutical and chemical sectors are rapidly shifting towards flexible, scalable reactor solutions suitable for cGMP and cleanroom conditions.

The changing dynamics in API production
The requirements within process development are changing significantly. Where fixed, large-scale production systems were previously the norm, the market now benefits from intelligent solutions that can respond quickly to new molecules, smaller batch sizes, and changing market conditions. A successful route from the initial idea to commercial API production relies entirely on the right combination of parallel synthesis, in-depth process understanding, and scalable reactor platforms.

Controlling critical process parameters
When scaling up chemical and pharmaceutical processes, the greatest challenge lies in maintaining process stability. Controlled scaling up places high demands not only on reliable reactor technology, but also on process knowledge and flexibility. Reaction conditions that succeed at lab scale must be seamlessly and reproducibly translated to larger volumes. Parameter deviations in temperature, pressure, mixing, or heat transfer can lead to unwanted by-products or yield losses.

For R&D and process engineers, it is therefore essential to build process understanding from the earliest development phase:

• Parallel synthesis: Enables multiple reaction conditions to be investigated simultaneously, providing faster insight into optimal process parameters.
• Step-by-step scale-up: Offers a safe, well-founded transition from small volumes through pilot scale to representative production.

Flexible reactor solutions from R&D to controlled production
Because the boundary conditions vary significantly per development phase, equipment agility is essential. Modular reactor platforms allow technology to grow alongside process maturity, across three consecutive phases:

• Screening & process optimisation: In the initial phase, the focus is on testing multiple reaction conditions simultaneously. By conducting parallel reactions, parameters such as temperature, pressure, and reagent ratios can be efficiently compared and fine-tuned.
• Scale-up & pilot scale: Once the process is stable, the step to larger volumes follows. By utilising scalable (pressure) reactors, the process is investigated under increasingly representative conditions while maintaining precise control over mixing and heat transfer.
• cGMP & cleanroom production: For the final step towards commercial API manufacturing, equipment must comply with stringent quality and cleanliness requirements. Specific reactor configurations and controlled conditions ensure a safe and reproducible transition.

From initial screening to final production, controlled scaling up hinges on deploying the right reactor technology at the right time.

Partners and technologies
To support this development chain, Suurmond offers modular reactor platforms. This involves utilizing SYSTAG’s parallel synthesis technology (such as the Flexycube) for the R&D phase, and BÜCHI reactors (including the miniPilot, midiPilot, and medium-scale pressure reactors) for further scale-up and cGMP production.

Written by

Suurmond BV

Read more