Thousands of years ago in China, people started fermenting rice and grapes to make wine. In a sense, they invented bioprocessing, which has since become rather more sophisticated. Today, bioprocessing is best understood to be about the manufacture of biotherapeutics. That may sound as though bioprocessing deserves a pat on the back. Well, yes, it does. But it also needs a nudge in the right direction. Bioprocessing needs to advance technologically if it is to overcome some significant challenges.
According to Bonnie Shum, a principal engineer at Genentech, bioprocessing must cope with healthcare’s growing complexities, which include budgetary pressures, while demonstrating more speed and agility in the development of new products. To meet these challenges, bioprocessing will need to implement new technologies. Doing so is a challenge in itself.
“There are high barriers for the implementation of technology, especially with innovative solutions that don’t fit the current paradigms of health authority regulations,” Shum declares. How might these barriers be overcome? Shum recommends “closer collaboration between innovators, end users, and regulators to define requirements and guidance on often uncharted territory.”
Such sentiments are held across the industry. For example, the need to hasten time to market is also emphasized by Pietro Perrone, PhD, an automation process engineer at Cytiva. “The patient’s needs are evolving with new conditions, and nobody wants to wait, especially when the impact is critical to the quality of life,” he insists. “New therapeutics need to get out of the starting gates faster with excellent quality to keep the industry reputable and the patients healthy.”
Even while adding speed, bioprocessing companies must avoid undue risks. “Applying risk management highlights the critical aspects of projects while identifying activities that have minimal impact,” Perrone explains. Risk management, then, can help companies set priorities when working with demanding timelines.
Accelerating bioprocessing requires investment and innovation. As Perrone points out, “Operations that can be started quickly and converted even faster will be at the forefront for the future.”
To get an overall improvement in speed in bioprocessing, though, more than industry must be involved. “Stronger communications and cooperation between manufacturers and regulators will also play a part in meeting ‘faster everything’ production demands,” Perrone observes.
One way to speed up changes in bioprocessing builds on the use of compartmentalized manufacturing suites. These suites can be set up quickly and modified as needed. Consequently, they allow a bioprocessor to make a quick change from one biotherapeutic to another.
Standardizing processes can also speed up various aspects of drug making. Perrone notes that standardization “will need to start at the drug product development stage for it to be scaled up effectively into manufacturing.”
Continuous and intense
One aspect of tomorrow’s bioprocessing, continuous methods, is already underway, but has a long way to go. Plus, these methods must be integrated into a complete facility.
There will be “an evolution toward what we call the biopharmaceutical manufacturing ‘facility of the future,’ which will be characterized by intensified, continuous, predictive, and autonomous operations,” says Darren Verlenden, head of bioprocessing at MilliporeSigma. “These are the cornerstones of the Bioprocessing 4.0 evolution.” According to Verlenden, MilliporeSigma’s research indicates that by 2025, approximately 30% of the commercial production of molecules will rely on processes that incorporate intensification technologies.
The transition to Bioprocessing 4.0 will require companies to upgrade specific tools. Verlenden notes that 90% of MilliporeSigma’s customers “realize that they need to upgrade their digital capabilities to leverage new process technology in the next five years.”
Continuous methods are also being sought to support the transition to Bioprocessing 4.0. “Continuous processing is one technology that is being developed to support robust, large-scale, and rapid manufacturing,” says Thierry Nguyen, PhD, director of biologics product development at Catalent. “Continuous processing is enabled through using closed systems and rapid microbial testing strategies, but regulatory acceptance needs to be in place to enable real-time release of drug substance and drug product.”
Despite the challenges of transitioning to continuous processing and gaining regulatory acceptance, some experts still see this as the most crucial trend for bioprocessing. According to Claudia Berdugo, PhD, director of process development at Catalent, “Continuous bioprocessing is probably the leading technology in biopharma with the best prospect for higher benefits of implementation.” She adds that the “known benefits include increased productivity, lower cost-of-goods sold, and a smaller facility footprint.”
Getting to all of those benefits, though, requires considerable effort. “Companies need to work on different aspects of continuous bioprocessing, including N-1 perfusion, production perfusion, continuous chromatography steps, and process analytical technologies,” Berdugo asserts. “Another area of innovation is in the analytical tools and technologies that offer rapid turnaround for development and characterization programs that facilitate moving quickly in the lifecycle of the product.” She adds that “cell line development technologies targeting higher productivity with potential for use in continuous processes are also being developed.”
Digitalized and data-wise
Many of the transitions ahead for bioprocessing will depend on collecting more data and using it in more effective ways. “The next great leap of evolution in bioprocessing will likely be driven by digital transformation,” Shum says. “The foundational changes have been building up significant momentum in the industry for the past few years.”
Shum welcomes the advances she has seen in digitalization, interconnected instrumentation, automation, and data-driven decision-making. She expects that these advances will bring about “significant improvements in overall productivity, reliability, and understanding of the processes.”
Most of the experts interviewed here maintain that doing more with bioprocessing data will require applications of artificial intelligence (AI). For example, Nguyen says that in the next decade or so, AI will facilitate operational improvements. “With digitization and AI-assisted operations,” he elaborates, “it will be possible to fully utilize metadata and generate predictions, enabling timely interventions and increasing the chances of success.”
Verlenden adds, “In the next decade, the technology evolution will be driven by intensified and continuous processing technologies, as well as data analytics and further integration of machine learning and AI in bioprocessing.” Methods for collecting this data are also changing. As Verlenden mentions, “We continue to search for innovative sensor technologies that allow for direct and indirect measurement of product quality attributes and process performance to enhance process control and understanding.”
In many cases, that data will be collected automatically. In fact, automation will change many steps in bioprocessing. “Automation will be a constant consideration for bioprocessing,” Perrone says. He also points out that the “needs, techniques, and approaches available in this industry will drive the implementation of automation from the laboratory to the production line and fill/finish operations that will transform best practices.”
Plus, once-isolated automated processes will be brought together to form an interactive whole. “As we move toward connected processing, individual unit operations will have the ability to communicate directly with adjacent systems, rather than in isolated batch processes as ‘islands of automation,’” Verlenden explains. “This orchestration of the control scheme across multiple operations allows for enhanced control of a manufacturing process, resulting in improved product quality and yield, while decreasing process time and labor cost.”
Since the detection of SARS-CoV-2, the virus behind COVID-19, it has never been clearer that the pharmaceutical industry must be as agile as possible. At any time, the industry may be called upon to expedite the development, manufacture, and distribution of entirely new biotherapeutics or vaccines.
“Despite the remarkable advances in biopharma,” Berdugo emphasizes, “there is still a need for accelerated programs to respond to the high demand for specific products.” She adds that in the future, such demand will be met with “flexible facilities and operation models, continuous training and improvement, and scheduling tools and operation software for monitoring and data management.”
Even the methods for delivering tomorrow’s biotherapeutics will evolve. According to Perrone, these methods will evolve, in large part, through the influence of nanotechnology. “Nanotechnology allows for more focused treatments,” he says. “It enhances the ability to target specific treatment sites rather than the whole patient.” Perrone suggests that if treatments are better targeted, they may be administered at lower doses, reducing the incidence of side effects.
More and better therapeutics
As the bioprocessing industry implements some of the changes described here, what will be the big-picture improvements? Nguyen says, “These changes should lead to increased success, increased efficiency, and reduced waste, enabling the real-time release of products.” In addition, Nguyen notes that these improvements “would aid in speedy deployment for emergencies, remote areas, and new plant commissioning.”
To reach the productivity levels expected in tomorrow’s bioprocessing, companies must “leave behind paper-based bioprocessing, data silos, manual process control, and instruments that cannot communicate with each other,” Verlenden says. “In its place will be a manufacturing ecosystem, seamlessly connected via uninterrupted data acquisition and analysis and characterized by information transparency and decentralized decision making.”
Ultimately, a patient’s experience determines the real success of bioprocessing. That’s exactly what Perrone emphasizes: “The patients should receive significant benefits from these changes, and these changes should result in better quality therapeutics and more availability of specialized therapeutics for conditions that exist in small patient populations.” Developing better therapeutics should always be the main goal of bioprocessing—in the present, in the near future, and beyond.