Transitioning to next-generation biomanufacturing is a strategic objective for large Biopharma
The demand for biopharmaceuticals continues to grow. Populations are aging in the mature markets such as North America and Europe. They need medicines to maintain their health and manage chronic conditions. With unprecedented amounts of information via digital technology, patients in growth markets are more aware of, and demanding access to, the latest medical technologies. There are many opportunities for biopharmaceutical companies to increase revenues but the path to success is not straightforward. The demand from patients is leading to escalating healthcare costs that many analysts fear are unsustainable. Policy makers in mature markets are grappling with the challenge of making patient care affordable and are increasingly asking pharmaceutical companies to demonstrate the value of their products. Rapidly growing markets across the globe have diverse medical needs and differing policies that determine how companies receive payment for their biopharmaceutical products.
Larger biopharmaceutical companies are experiencing increased competitive pressures. Biosimilars are likely to erode the margins of products that were once ‘cash cows’. Expensive drug development programs have not always delivered the blockbuster innovator drugs that would offset the revenues lost to generics. Large pharmaceutical companies have spun-out biotech business units to increase their market focus. Small start-ups with specific expertise and focus on new therapeutic approaches such as cell therapies have the chance to disrupt the industry.
There is plenty for biopharmaceutical executives to reflect upon. Investors have called for greater discipline in product portfolio management, measures to cut bloated cost structures and even further break-ups. Optimizing a firm’s global biomanufacturing network will be one piece of the jigsaw through which they can achieve competitive advantage.
Process innovation driven by the changing needs of global networks
Companies need increasingly efficient manufacturing processes to reduce their Cost of Goods. Such improved efficiency must come without a detrimental effect of product quality, which is under ever-greater scrutiny. A firm must be able to modulate its global manufacturing capacity and avoid drug shortages. It must ensure it can supply its products to markets that are further than ever from home. The larger quantities of biologics needed to support increased patient demand are stretching current production technologies to their limits. These necessities are stimulating process innovation and is the context in which engineers are investigating continuous or intensified biomanufacturing techniques.
Biopharmaceutical companies will be hoping that through process intensification they can avoid having to build and operate large-scale, stainless steel manufacturing facilities with multiple bioreactors having a capacity 10,000 liters of or more. Building these large facilities is both expensive and risky. Design and construction must start before uncertainties around the quantities of the product a biotech company intends to manufacture are fully resolved. If the product fails at one of the final hurdles before commercialization then there is a danger they will have squandered their investment. These large facilities are relatively inflexible and difficult to repurpose to produce a different product. Scaling processes up to such a big scale can be fraught with challenges for engineers.
Process intensification will help
Developing intensified processes can help avoid these challenges. Perfusion-based production platforms provide companies with the opportunity to produce both stable proteins like monoclonal antibodies and labile-proteins that could degrade in a batch culture. This option increases agility within a firm’s global manufacturing network if a company’s pipeline contains both types of drug modality. Companies increase production capacity by adding additional production modules of the same scale rather than larger scale production equipment.
Perfusion cell cultures performed in 1,000 liter or 2,000 liters can produce large quantities of protein over a 30 to 60 day period. Using bioreactors with a smaller size enable the utilization of flexible, single-use technologies and a reduction in scale-up risk. Single-use bioreactors, even at the 2000L-scale, are now capable of providing such high oxygen-transfer rates that they permit lower gas flow rates than stainless steel vessels and provide comparable cell culture performance.
Intensified, multi-column chromatography technology allows this quantity of protein to be captured without recourse to large-diameter columns while providing efficiencies in both resin and buffer consumption. The industry is experimenting with other approaches such as Sanofi’s Accelerated, Seamless Antibody Purification strategy that the company can perform with membrane adsorber technology permitting single-use processing.
What could hold back the widespread adoption of highly intensified processes?
Although a more continuous approach seems likely to lower operating costs when annual drug demands are high, the reduction in operating costs may not be so significant in cases where the amount of drug required is smaller. Perfusion processes, for example, typically require large volumes of expensive cell culture media. Additional infrastructure requirements required to keep upstream operations running continuously may partially offset the decrease in process footprint.
It will take time for companies to adapt to the more sophisticated equipment and control systems that continuous processing is likely to require. They will need to understand where processing risks are likely to occur and how they can mitigate them.
Yet, as an industry insider recently pointed out to me, continuous processes should be more predictable even if they require equipment that is more complex. Perfusion cultures that reach a steady-state should be less prone to those variations engineers experience in fed-batch cultures that can affect product quality.
Different approach to implementing continuous processing platforms
Companies will differ in their readiness to adopt significant changes to bioprocess configurations. Some industry players with experience of perfusion culture will be more comfortable applying the production technique across their networks. Those with less experience will find more incremental improvements to existing platforms that increase productivity without creating purification bottlenecks.
A platform-based approach seems to be the most promising strategy and will reduce development times, increase speed-to-clinic. It reduces engineering costs and helps standardize operations even for companies with complex pipelines. Companies will continue to investigate robust continuous or intensified bioprocess platforms that will allow them to provide patients around the world with lifesaving medicines and gain competitive advantage through optimized biomanufacturing networks. No doubt, exciting times for every bioprocess engineer!