Ditch batch: continuous is the future

Hosted by UK consultancy firm Scientific Update, the roundtable discussion considered whether the benefits promised by continuous processes can be effectively exploited by the fine chemical and pharmaceutical sectors. Trevor Laird, founder and CEO of Scientific Update, commented that a key factor deterring these industries from adopting continuous processes is the flexibility that batch processing offers. "The question is whether there is enough new technology around that will allow these processes to be converted into continuous manufacturing,"​ Laird said. The US Food and Drug Administration (FDA) has been relatively scathing in its criticism of pharma's apparent lack of willingness to convert to potentially more efficient processes, stating in a white paper on pharmaceutical manufacturing improvement that "pharmaceutical manufacturing operations are inefficient and costly…Low efficiency is predominantly due to 'self imposed' constraints in the system…These constraints keep the system in corrective action mode."​ As part of the session on continuous processing and its potential in pharmaceutical/chemical manufacturing, Laird suggested that processing equipment such as microreactors could present an effective solution. Eliminating the problem of costly, dedicated plants required by traditional continuous processing, small continuous microreactors retain the flexibility of batch manufacturing whilst bringing a host of added bonuses such as better selectivity a high temperatures, high throughput, and are suitable for fast reactions and reactions with unstable intermediates. Laird also highlighted that the often-problematic task of scale-up could be less of a challenge using microreactor technology: "What it allows is instead of scaling up…is the idea is that you 'number up' - i.e. that you have a multitude of reactors rather than a larger scale operation,"​ he said. "This gives you the advantage of moving quickly from laboratory through to pilot plant and manufacture." Several companies have already taken the initiative and started on the continuous processing path. Lonza, particularly, has thrown its weight behind the technology, working directly with microreactor manufacturers to develop flexible systems that can be used on the multi-kilo and ton scale, and successfully scaling up some of the resultant processes. French/Swiss firm AETDEV has also developed reactor technology in this area, with DSM and UK firm Phoenix Chemicals also achieving the yield and efficiency improvements that continuous processing technologies can bring. While it is fine chemicals firms that seem to be leading the pack and driving forward with continuous processing technologies, pharma companies are keeping their eyes on developments as well. With firms such as Organon and AstraZeneca already beginning to use microreactors for some processes, and the recent $65m hook-up between Novartis and MIT to 'revolutionise' pharmaceutical production with continuous manufacturing, the sector looks ripe for growth over the coming years. Despite the apparent promise continuous processing seems to offer, Laird cautions that it is likely to be some time before the technology is widely implemented in pharma manufacturing practices. The new technology still has some way to go before is it sufficiently developed to lure manufacturers away from their comfort zone of batch-based manufacture, but Laird seems to think that the challenges that lie ahead can be overcome.. "We're really just at the start of this and there are a lot of problems still to be solved,"​ he said. "What we're seeing at the moment is individual steps in the synthesis being done continuously, but the rest by batch. I think to get the whole lot integrated is going to be quite tricky, but it's something to aim for."