Life Sciences Focus: Process Development
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Continuous manufacturing and the personalized medicine revolution
As the pharmaceutical industry moves towards the development of personalized medicines, manufacturing processes must adapt to match demand. This article explores how continuous manufacturing, combined with digital technologies, is providing the flexibility to produce on-demand, specific therapies for small patient populations.
N
o two people are exactly alike and, as a consequence, the vast majority of drugs are
effective in just 30-50% of the population. [1] In spite of this, two patients with completely different pathologies will often be prescribed the same treatment for a given illness. Advances in genomics and biomarker identification in recent years have driven the pharmaceutical industry away from a ‘one size fits all’ trial-and-error approach to medicine. Increasingly, the focus is on
creating therapies that are specially tailored to the patient. Biomarker research constitutes an important part of the personalized medicine revolution, allowing medical professionals to predict disease progression, identify the class of drugs that a patient will respond to best and create a customized treatment plan. In order for patients to fully benefit from personalized medicine, however, the whole pharmaceutical industry must adapt its processes to enable specialized drugs to be manufactured and distributed in smaller volumes than is currently the norm. From reconfiguring supply chains to implementing new technologies, such as continuous manufacturing and artificial intelligence (AI), it is clear that a number of changes are on the horizon.
The manufacturing process is evolving to meet demand Advances in continuous manufacturing technologies have emerged as one solution to the challenge of manufacturing drugs cost-effectively on a relatively small scale. In contrast to traditional
22 Dr Gareth Jenkins, CSO, Arcinova
batch manufacturing, in which drugs are manufactured through a stepwise process, continuous manufacturing is more flexible and allows drugs to be manufactured non-stop as reagents and solvent continuously flow through a reactor. When applied to the production of personalized medicines, the benefits offered by continuous flow are manifold. For example, continuous manufacturing often eliminates the need for chemical engineers to develop a series of ever- larger, specialized reactors to accommodate scaled-up production – which can be highly labour intensive. Instead, drug manufacture can be tailored to demand. If a personalized medicine is targeted at only a small percentage of patients, fewer or smaller reactors need to be dedicated to the task of manufacturing it. Equally, if demand goes up, it is a simple matter to run the process for longer, or devote more reactors in parallel to the production of that particular drug. This capability can help to accelerate the drug to commercial
manufacture and deliver it into the hands of patients more quickly. In addition, continuous manufacturing technology enables chemical engineers to safely access much more challenging reaction conditions, including hazardous reagents and extreme temperatures. Using continuous manufacturing can enable chemists and chemical engineers to produce a wider range of molecules and unlock new synthesis routes to complex personalized medicines. Furthermore, a continuous process also lends itself to continuous monitoring, which can help increase confidence in product quality. Finally, continuous manufacturing can facilitate a reduction in the requirement for high volumes of organic solvents. This not only improves cost-effectiveness, but also reduces waste. As the industry moves towards greener manufacturing principles, this important environmental benefit can help drug manufacturers to reduce the footprint associated with drug production.
Reconfiguring supply chains
The current pharmaceutical supply chain is based around delivering large quantities of a given drug for widespread use. Switching to small-scale production of more specialized drugs presents logistical challenges. Creating personalized medicines on a small scale means manufacturers will not be able to benefit from the economies of scale, and it is expected that CDMOs that have invested in cost-effective solutions such as continuous manufacturing technology will have an advantage in this area.
Another challenge is ensuring
that specialized drugs are correctly delivered to the intended patients, despite the increased complexity of a supply chain that involves shipping customized products directly to specific individuals. Consequently, as the personalized medicine sector grows, logistics providers may adopt techniques that will improve efficiency and visibility to prevent any errors of this sort from arising. To this end, advanced GPS tracking and automatic alarm systems, should the delivery go off-track, may be of benefit in future. [2]
AI, Pharma 4.0 and the future of drug manufacture Pharma 4.0, a popular buzzword for the incorporation of the latest digital advances (such as self- learning machines and smart data management) into processes within the pharmaceutical industry, offers up numerous exciting opportunities for personalized medicine manufacture. In particular, the increasing level of automation can facilitate the creation of intelligent networks across the development pipeline. Machines may be able to predict failures, and trigger essential maintenance automatically, to sidestep issues before they arise. [3] Currently, production managers can spend significant amounts of time troubleshooting quality control errors that occur during manufacture. For example, if the raw materials used are of insufficient quality, using traditional methods this may not be detected until the batch of product had been completed. Continuous manufacturing combined with
Summer 2020
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