Continuous Manufacturing: Novartis' experiment in the future of drug production

Continuous manufacturing has long been touted as the future of drug production. Pharmafile approached Novartis for more details about its successes in the area, and the challenges, of developing the new process.

Why did Novartis decide to take the step to experiment in continuous manufacturing processes? 

In a rapidly evolving industry climate, Novartis is leading the drive for more innovative production and manufacturing solutions. Current drug manufacturing – the "batch method" – can be a laborious, segmented process, requiring significant time, resources and financial investments. Before reaching a patient, products often pass through multiple phases of manufacturing at various facilities across hundreds of miles before being ready for distribution. Novartis – recognising the need to deliver treatments to patients faster and more efficiently, and the limitations of the current manufacturing process to meet those needs – is working to transform the pharmaceutical development and manufacturing process through continuous manufacturing.

What are the advantages to continuous manufacturing?

The innovative continuous manufacturing process integrates all steps of production from start to finish into a single process in one location, allowing for strong quality control, lower costs and better production speed. Additionally, when compared to the batch method, continuous manufacturing:

• Runs 24 hours, seven days a week with very brief throughput times. By comparison, the current method is continuously interrupted and requires roughly a year just to produce one batch of pharmaceutical products. Continuous manufacturing shortens the development and manufacturing time, which means medicines get to patients sooner and production costs are reduced
• Strengthens product quality and reliability through the sequential but continuous processing of small amounts of material rather than simultaneous processing of a few large amounts, which allows for much more stringent process control throughout each step
• Uses smaller equipment, infrastructure, and buildings, removing costly and inefficient heavy machinery from the production cycle. The entire operation can be completed in one room
• Reduces carbon footprint by eliminating process interruptions, intermediate storage needs, and material transport

There was a lot of talk and speculation regarding continuous manufacturing last year but it seems to have gone quiet recently. Is this due to companies working on the actual technology and infrastructure involved, or is progress stalling?

At Novartis, we remain more committed than ever to the continuous manufacturing process, and continue to see progress in this area. This continues to be an area of great priority to our company, and is the wave of the future of manufacturing. We don’t feel that progress has in any way stalled or that the excitement surrounding this field has lessened, rather we work in an industry that is highly regulated, and with that comes a certain pace of progress – a pace which most people feel we are on track with.

Novartis entered a 10-year research collaboration programme with the Massachusetts Institute of Technology (MIT) back in 2007 – have there been tangible outcomes to this collaboration?

The partnership established the Novartis-MIT Center for Continuous Manufacturing (CCM). The goal of this ongoing collaboration is to research and develop novel pharmaceutical production techniques. In pioneering this field, we challenged ourselves to be creative and move beyond the traditional ways of manufacturing drugs, and we knew we needed a partner that embodied that outside-the-box style of thinking. That is exactly why we chose to work with MIT to concept this process for the pharmaceutical development sector. We then implemented their learnings, creating our cGMP-compliant pilot facility to produce and supply clinical-trial materials, which includes approximately 3,200 square feet of cGMP space and all newly designed equipment.

You now have a continuous manufacturing facility in Basel – what have you learnt from getting the facility up and running?

The learnings from operationalising this system are vast. For example, every piece of equipment in our facility required varying levels of modification to meet the unique needs of continuous vs batch methodology. However, perhaps the greatest wisdom gained from this process has been the true value of partnership and collaboration across our industry and outside of it. We spearheaded new ways of thinking by partnering with and learning from MIT; we continued to succeed in progressing this approach because we worked with regulators at every step of the way; and we’ve kept our approach open to anyone interested in learning from or using it, so that everyone in our industry can benefit from it, to the ultimate benefit of patients. Open-mindedness in the face of disruption is absolutely critical to succeed when you’re taking on a project of this calibre and with this scale of potential change to the ecosystem.

Being at the forefront of new types of production will always mean that you will encounter difficulties – what has been the most challenging aspect of getting the facility functional?

Disruption of any kind requires open-mindedness, and the ability to be bold and take risks while understanding that you will need to learn and adapt constantly. The healthcare industry is one of the most highly regulated in the world, and we have a tried and true way of producing drugs, which makes some people uncomfortable with changing our operational structures and norms. At Novartis, we are constantly challenging ourselves to ask those tough questions, always with the goal of driving better outcomes for our patients by delivering innovation as effectively and efficiently as possible. While change of this scale can be a challenge to overcome, the response from all parts of the healthcare ecosystem has been positive and accepting when it comes to adopting continuous manufacturing approaches. The ongoing challenge and opportunity comes from continuing to expand the network of people and companies joining us on this journey in order to disrupt not just a handful of companies, but the whole ecosystem.

It has been mentioned that the facility was being out-licensed, meaning that others could learn from what Novartis had developed. This could be viewed as unusual in an industry that is usually highly secretive about its innovations – what was the reasoning behind this?

From the inception of our programme, it was understood that a core function of our strategy would be to build first-class capabilities in an open manner, to the benefit of our entire industry. While we retain rights to the technology, we not only enable, but encourage others to enter this arena with us so that we as an industry can make this important step towards more efficient and effective processes. At Novartis, we felt that this was a critical step to ensure this approach is successful. We need to be coordinated with many others from our industry to make headway, as we cannot do it alone. We are and intend to remain a leader and catalyst for progress in this space, but want to work in collaboration with the rest of the healthcare industry to ensure that what we do ultimately delivers benefit to as many patients as possible around the world.