Small molecule *API manufacturing* \\Adrian La Porta
Small molecule APIs remain the backbone of global medicine, but the manufacturing systems behind them are decades old, inefficient, and increasingly unable to keep pace with what the science is producing. In this film, Technical Director Adrian La Porta explains why the conventional batch manufacturing model is failing and sets out a practical alternative built on miniaturisation, automation, and systemisation.
When we go small, we can go flat:
The question is straightforward: can the manufacturing networks for these molecules produce higher volumes of more complex products, for more patients, faster, at lower cost, while eliminating their environmental harms? The honest answer, as Adrian sets out in this film, is that they cannot – at least not in their current form.
A model that hasn't changed in decades
The factories that make small molecule APIs still rely on batch chemistry in large, multipurpose vessels. The model persists because of its flexibility – the same vessel can be used for reaction, distillation, extraction, and crystallisation. But that flexibility is largely theoretical. In practice, changeovers between products require dismantling, cleaning, and inspection that can consume 40% of plant capacity. The vessels are optimised for none of the operations they perform. And because the entire system is predicated on manual operations – people loading solids to start and end every batch – there is a structural incentive to make batch sizes as large as possible, which in turn drives vessel size upward in a vicious cycle of diminishing efficiency.
Larger vessels hold larger quantities of hazardous solvents, requiring more extensive safeguards. They need larger utilities, larger chemical supply systems, larger waste treatment systems, and larger bespoke industrial buildings. The fluid volume of the process becomes a small fraction of the volume of the facility it sits in. Process equipment cost becomes a small proportion of the overall capital cost. The building, not the chemistry, is where the money goes.
The alternative: miniaturisation, automation, and systemisation
Adrian's argument is that scientific and engineering advances already provide a new paradigm – if the industry is willing to discard preconceived ideas about how pharmaceutical manufacturing should work.
Process intensification – including but not limited to continuous processing – enables smaller, faster, more efficient operations that reduce waste and improve quality. Miniaturisation of batch processing, integrated into hybrid facilities, removes the scale, cost, and hazards of conventional plant. And automation is the crucial enabler: it breaks the link between the number of batches and the number of people, eliminating the structural incentive to scale up.
The benefits cascade. Smaller equipment is safer and easier to move. When pipes become small, their design and fabrication become simpler and cheaper. Whole process trains can be built off site. As high-value process systems shrink, they can be decoupled from the buildings they sit in – greatly reducing complexity and cost. Utility loads shrink. Single-level operations become possible, easing maintenance and enabling automated guided vehicles.
Miniaturisation also opens the door to distributed production. API supply is currently super-globalised, with many APIs made in just one or two plants worldwide. Smaller, standardised, skid-mounted manufacturing units – factory built, transportable, reusable from process to process – offer a more resilient model that can help address medicine supply security.
As Adrian puts it: when we go small, we can go flat.
Why it matters
The need for affordable, sustainable medicines is urgent and growing. The advantages of integrating the best of chemical manufacturing and automation technologies are compelling. The challenge is not technical – it is cultural. Every system, facility, organisation, and regulatory framework in the industry has been built on the assumptions of batch processing. Changing those assumptions is hard. But the case for doing so is no longer optional.
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