The biopharma industry can be cautious when it comes to change and new manufacturing technologies, which is understandable given the temperamental nature of cells and the inherent difficulties of biopharma manufacturing. Single-use systems offer a range of benefits including reduced cleaning, increased flexibility and decreased footprint, but many in the industry were wary when the concept was first introduced many years ago. As use has increased, the technologies have become well accepted by users and regulators alike.
Perhaps the main challenge is the limits of scale; single-use systems are generally more suited to small-scale production, but this also makes them highly appropriate for continuous bioprocessing operations. Continuous bioprocessing is a relatively new concept that allows more economical production – but flexible technologies are key to its implementation. Pall recently announced its intent to focus on continuous bioprocessing and has been exploring options and technologies. We speak to Mario Philips, Vice President and General Manager of Single-Use Technologies at Pall, to find out why single-use systems are key to making continuous bioprocessing a reality.
How have single-use technologies evolved?
Single-use bags have been used in a number of industries for storage, but the biopharma industry has taken this one step further by performing operations, such as mixing, directly inside the bag. At the end of the day, single-use bags are just plastic, but this plastic is highly complex and must also be delivered at a high degree of quality for biopharma applications.. Over the last 60 years, Pall has built up a huge credibility in filtration and has gradually moved into single-use technologies. Initially, the company started out with sterile connectors before moving into storage and downstream single-use processing. In 2013, Pall also acquired ATMI’s life sciences business, which gave the company access to a portfolio of upstream single-use technologies. More recently, we’ve gotten involved with continuous bioprocessing and have launched systems for continuous purification (BioSMB), continuous clarification (Cadence Acoustic Separator) and tangential flow filtration (Cadence Inline Concentrator). The biopharma industry can be quite conservative when it comes to adopting new technologies, but there is no question that single use is getting more mature and is here to stay. Single-use systems are usually combined with stainless steel in a hybrid approach, but some new factories are being built to use single use almost exclusively. In the early days, the biggest challenge for the single-use market was uptake – it’s difficult to change the way that the industry does things; the fact that the ultimate end user of biopharma products is the patient means that changes in biopharma are never taken lightly. Today, however, the value proposition of single use is well understood and companies are very comfortable with the technology. In particular, Pall has focused on ensuring that single-use technologies are fit for purpose, as well as being reliable and easy to use; after all, if an operator cannot use and install the system correctly then it’s meaningless. When talking about single use, we shouldn’t forget about connectors, which also need to be reliable and easy to use.What are the next steps for single use?
Single-use bioreactors have gained a lot of momentum over the past few years. To some extent, single-use tangential flow filtration is seeing more interest too. We’re also at the point where some people in the industry are talking about single-use facilities. The market is filled with different customers with different visions and single use is a great way to create more flexibility in a facility. Although some small customers may buy a complete single-use factory, I don’t think that large companies will give “the keys of the factory” to just one vendor. When using single-use technologies, you become reliant on vendors for ongoing supply of bags and other components. Most companies don’t like to rely on just one vendor, so they typically divide the process up and use different vendors for various upstream and downstream processes, as well as retaining some independence with stainless steel. That said, as single-use technologies have matured and gained greater acceptance, many customers have realized that relying on a large vendor is nothing to be nervous about. A big company like Pall isn’t just suddenly going to disappear and is also experienced enough to help ensure a consistent supply of consumables. However, there is still a lot of work to be done in terms of modular design. As a vendor, we supply the equipment and we can recommend that the company places a bioreactor here, a mixer there, tangential flow filtration here, and so on, but the customer still has to figure out how to connect everything. The next step will be for vendors to help with modular design via pre-fabricated manifolds that allow customers to easily connect everything to get the process up and running quickly. In turn, this will also lead to standardization.
How is single-use affecting continuous bioprocessing?
Continuous bioprocessing has been discussed on and off in the industry for over a decade and there have even been dedicated conferences where everyone came together to discuss the problem – but then nothing happened. Neither manufacturers nor vendors were committing – but this is starting to change. As my colleague, Michael Egholm, discussed in a previous article (https://themedicinemaker.com/issues/0616/breaking-the-bioprocessing-mold/), Pall has taken the decision to try out continuous bioprocessing because we believe in its potential. As a first mover in this field, we are learning a lot and solving many problems, which will help us to be even more innovative in the future. Single-use technologies are a real enabler in moving forward with continuous processing because they can help to make processes more flexible and modular, and are essential for connecting different operations. At the moment, I don’t think most companies are ready to go continuous. We are introducing our continuous bioprocessing systems gradually to allow customers to get used to them. At first, I think our customers will use the systems as unit operations but as they become more confident they will start to consider full bioprocessing. The “sweet spot” for single use is around 2000 liters because larger bags are tricky to handle. Some companies need large volumes, but producing a product continuously means that smaller equipment can do the job. The industry won’t need 10,000-liter bioreactors anymore, which saves a lot of factory floor space and capital investment.What are your thoughts on the future of biopharma?
Continuous bioprocessing will only be used for new products. I don’t believe there will be a market for retrofitting an old batch process to a continuous process for a marketed product. For single use, it’s a different story because it’s relatively easy for companies to replace certain stainless steel unit operations with single use. I’m sure we all agree that biopharma is a fantastic industry. At the moment, it’s very exciting because we are seeing a shift not only in manufacturing technologies, but also in how we look at treatment versus cure. For example, there is a lot of hype around next-generation gene and cell therapies, which can cure patients. There is now a huge need for us, as suppliers, to help scientists realize their dreams. We can never impact the life of a patient in the way that a biopharma manufacturer can, but we can help those manufacturers scale up their operations. I genuinely believe that the future of biopharma manufacturing lies in flexibility – and that means single-use technologies and continuous processing. Pall is no longer a filtration company; we have become a bioprocessing company and our role is to help our customers from a process perspective, so they can concentrate on the science and clinical trials for their treatments.Newsletters
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