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Continuous manufacturing

The term ‘continuous manufacturing’ doesn’t sound particularly efficient or environmentally friendly. You’d think switching something off once in a while would be the best way to be greener.

But actually, when it comes to manufacturing the active ingredients in medicines, continuous manufacturing can be environmentally friendly. In fact, by keeping machines running 24 hours a day, we’ve found that waste can be dramatically reduced. And that’s not the only benefit.

This continuous process – which we have been experimenting with since 2003 - is essentially a different way of making the active ingredients in medicines. The traditional method uses large-scale industrial processes - involving heavy machinery - to manufacture an active ingredient in batches of up to 1000 kilo batches at a time.

In the traditional process, the main piece of machinery is the batch reactor. This is where the synthesis of the active ingredient occurs. Typically, we would use a reactor of about 4000 litres, and after each batch is produced, the reactor, which weighs around five tonnes, would need to be cooled, cleaned and recharged - using up time and energy and producing waste.

With continuous manufacturing, we can make lower volumes but much more quickly, in smaller reactors based on flow through a pipe. Indeed, one of our test reactors has been reduced to about the size of a pen. And because production is continuous, we don’t need to stop, cool or clean the reactor.

Image: Left - one of our new 'continuous' reactors. Right - a traditional vat-style reactor

 

a small reactor and a large reactor

 

By using this approach, tiny flows of 1 to 200ml per minute (to put that in perspective - 1 ml/min is a few tear drops once a minute) can be as productive as a 4000 litre traditional reactor if operated 24 hours a day for 300 days a year.

How it works

The simplest way to think about traditional manufacture of active ingredients is like cooking on a large scale. You add pre-weighed chemicals together in a controlled way (a recipe) to a large stirred reactor (cooking pot), and react (cook) for a set time. In this mode of manufacture, the actual manufacture of the product is only a small part of the cycle time - the rest is lost adding your ingredients, heating them up, and getting them out.

In a continuous manufacturing system the chemicals are pumped continuously into a small channel or tube, typically a few mm in diameter. This is designed to precisely control the chemistry so that by the time it leaves the tube your product is made, so no time is lost heating, cooling and discharging.

Making products in this way will help shrink the size of our factories, dramatically reducing the amount of resources consumed to make every kg of product.

Andrew Rutter, one of our engineers, is working with a multidisciplinary team in R&D and manufacturing to make the technology a reality. “Applying this technology can dramatically change our factories. As an example, in one of the processes we are developing; the water use is reduced by 83% and solvent by 42%, leading to a 52% reduction in conversion carbon footprint. The precision and speed that continuous reactors provide also allows for consistent control of product purity. At the same time we are making product in days rather than the months or years it takes to make to the product the traditional way. Ultimately, this will allow us to respond much more quickly to patient needs.”