The calls for the pharma industry to adopt continuous processing has been an ongoing one, whether it comes from regulators or from industry analysts, the topic is never far away when discussing improving the efficiency of manufacture.
As other improvements to processes also filter through, such as the growing uptake of single-use technology and the increasing digitalization of manufacture, the adoption of continuous bioprocessing could be facilitated.
A report by Deloitte suggested that the advantages of the technology for biologics are the smaller footprint and lower scale-up requirements once the process has been adopted. The report did note that there are challenges to address in the form of quality control.
However, when BioPharma-Reporter (BPR) spoke to Peter Levison (PL), executive director of business development for Pall Biotech, he suggested that with the amount of data generated and captured through continuous bioprocessing can benefit the final quality of the product.
BPR: What have been the major changes recently in the industry and how does this influence adoption of continuous bioprocessing?
PL: The intensification of processes, the higher titers, the greater potency of the drug – this has really reduced the numbers of liters of cell culture pharma companies need per year. The consequence is that bioreactor sizes, in many instances, are dropping and that then enables single-use applications and continuous applications. In essence, 2,000L single-use bioreactors, and multiples thereof, are well-designed to handle single-use batch and single-use continuous operations.
BPR: How can companies look to implement continuous bioprocessing?
PL: We suggest to clients that rather than go down a traditional approach of an end-to-end process, which could be all stainless steel or could be a single-use batch, or fully continuous, that perhaps they start looking at hybrid approaches – where you select the most effective unit operation for each individual stage of the process. By mixing and matching continuous techniques with batch techniques this will provide a more efficient and effective process solution.
With the portfolio of process tools available today, the toolbox is very large and probably never before has the process development community had as many technology platforms to choose from. So, hybrid processing is really an area to focus on and Pall Corporation, as a company, offers scalable process solutions for stainless steel applications for single-use batch applications and single-use continuous applications.
BPR: How do you see bioprocessing evolving in the coming years?
PL: In terms of moving forward, with the advent of Industry 4.0 and the trend towards automation and digitalization, we see that manufacturing strategies are going to move towards process optimization. This should improve facility utilization and productivity, which leads to improved product quality and enhanced patient safety. This is really where we see the major benefits of continuous bioprocessing.
BPR: Specifically, what technologies are already being used that are changing the process?
PL: Virtual reality and digital twins are being used to design facility layout and optimize equipment, to evaluate various production scenarios and create risk mitigation strategies. We use virtual reality to create a digital twin of a process facility and then you can enter these facilities in virtual reality and take a tour – you can see equipment layout and footprint; you can establish the ergonomics and the fit within the facility to ensure that the operators can work in a suitable environment. You can also build in space for additional equipment because these virtual reality technologies that we use are all to scale. So, you can start to design a facility with expansion in mind, if you need to put some additional equipment in there, as part of your risk mitigation strategy, then this can be done.
Analytics and control will add to that vision. In our Westborough, Massachusetts facility, we have put automation and control into the lab. This provides us with equipment and instrumentation control and data collection. Additionally, the system has the capability to provide shutdown control and information about any consumable changes. The system can perform multivariate data analysis to analyze the large number of data sets that we get in continuous chromatography.
BPR: How is data generation different between batch and continuous?
PL: In batch processes, the amount of data generated is relatively finite because the process has a very defined time period and you collect data at set time limits. Whereas continuous is running 24/7, for as long as you determine you want to run it for. So, there is a need to collect data as frequently as possible and as close to line as possible. So, a lot of efforts are being made to do inline monitoring or atline monitoring, and data can be generated pretty much in real time. The number of data points that will be generated is going to rise significantly.
The data has to be captured, it has to be stored and it has to be analyzed. If it isn't, the data becomes redundant and this really defeats the objective – but by having more data, you actually have more control over the process. The quality should improve because you know what is really happening in real time. And if quality improves, there should be benefits in terms of patient safety. So, it's a win-win situation.
BPR: What are the questions you hear most frequently from the industry on continuous?
PL: ‘What is the adoption and acceptance curve to these sorts of technologies and what might be the advantages?’ I think the way we present and position it is twofold. Firstly, not trying to advocate one technique only, we're saying you can use this big toolbox of techniques, which you can pick and mix from to give you incremental improvements. It's not all or nothing, you can do it in incremental stages.
We can offer a fully continuous solution, but that may not be necessary in everyone's application. There could be certain stages of a process that need not be done continuously. In that instance, it may be more comfortable and easier to handle the risk by working with the conventional processes. So, the toolbox we have and the portfolio premise at Pall is a great enabler for this.
The other aspect that we may get asked as well is: do we have evidence that it all works? We are very much a data driven company and we do have our continuous laboratory and application scientists generating technical data – both with our customers but also our own use to support our commercial activities. And this, if you like, provides the confidence that these technologies do actually work, because it is important to demonstrate that.
Peter Levison is executive director of business development for Pall Biotech and is responsible for developing strategic partnerships within the biotech community through the management of a network of global thought leaders, working with key industrialists and academics around the world.