This article was originally published by Bioprocess Online on October 13, 2022.
As the range of applications for cell and gene therapies expands from rare diseases affecting hundreds of patients to more common illnesses affecting millions, biopharmaceutical companies need scalable technologies to meet the growing demand for cells and cell products, particularly viral vectors.
Scaling production to meet demand often requires therapy developers to make a choice between adherent and suspension cell culture platforms. Each has advantages and disadvantages depending on cell type, desired output, timing, available production space and labor, cost, and other factors.
Adherent platforms offer advantages including superior cell productivity but scaling adherent platforms to meet production requirements can involve burdensome manual manipulation of a large number of cell culture vessels, increasing the risk of human error, and require extensive incubator and cleanroom footprint. On the other hand, suspension systems, such as stirred tanks, offer high capacity and automation, but they may require time-consuming and costly conversion of attachment-dependent cells and more downstream processing.
The preferred solution for many applications would be a system that combines the productivity advantages of adherent cell culture and the scalability, automation, and control of a suspension system.
For years, the Corning Research and Development team has applied its innovation process to address this customer need. This process begins with customer intimacy — dynamic engagement with customers’ scientists to understand their challenges, pain points, and desires. Corning field applications scientists, sales representatives, and scientific support personnel gather intelligence and discuss challenges and bottlenecks to customer productivity. We then leverage Corning’s many decades of materials science expertise and deep understanding of cell biology and behavior to develop potential solutions.
As we explore multiple paths to a potential solution, Corning’s engineers and scientists consider questions like, “What facilitates efficient cell attachment to a surface?”, “How do we dramatically increase cell density while ensuring cell health and productivity?” and “How can customers scale production from the lab to commercial scale with minimal technology transfer?” Brainstorming sessions eventually lead to internal testing of design prototypes, which are presented to collaborating customers for feedback: what helps solve their problem, will or will not fit their workflow, and what opportunities are there for improvement?
This iterative process continues throughout the development cycle. Once the product nears final design, the Corning team’s focus shifts to testing the consistency and repeatability of the new product or component, which can result in changes to the original design. Again, those changes undergo internal and customer testing. It is critical that we translate our understanding of each customer’s need into our products’ manufacturing design.
Corning uses engineering models to further streamline and refine the process, ensuring the product’s design delivers measurable and controllable performance results. A real-time feedback loop is initiated with internal teams and customers to confirm the product’s value proposition while bolstering our relationship with our customers, building trust, and instilling familiarity with the final product.
When a prototype is sent to customers for testing, they apply their own processes and systems to validate the product. Because Corning Life Sciences supports scientific research and cell production across numerous application areas, we often bring a different perspective than our partners in academia and industry. We work in synergy with these collaborators to provide mutually beneficial interactions throughout the development process. For example, a customer-informed redesign may help the product fill a gap in a specific process or can help better define areas for improvement in a customer’s workflow. This context applies not only to product design, but to manufacture, quality, shelf life, and/or storage conditions, with the outcome resulting in a win-win for both Corning and our customers.
This is a continuous process in the typical product lifecycle: even after a product has launched, a second-generation version is frequently already in the works to address emerging challenges or opportunities for improvement. As product usage increases, nice-to-have features are identified and prioritized for implementation, as are product improvement ideas and concepts fueled by emerging technologies and areas of research.
A recent example of this collaborative process is the development of the Corning® Ascent® FBR System. Developed to address the challenges of cost-effectively manufacturing large quantities of adherent cells to support advanced therapies, this novel fixed bed bioreactor platform is designed to deliver significant surface area intensification and high-yield bioproduction capability in a platform that scales from benchtop process development to commercial production. The collaboration with customers through alpha and beta testing resulted in valuable design improvements, resulting in a completely closed system with integrated controller, media conditioning vessel, bioreactor vessel and sensors.
One of the key unique features of the Ascent system that is also the result of multiple iterations is its woven PET mesh bioreactor substrate. This allows uniform flow of media, nutrients and transfection reagents throughout the reactor resulting in homogenous cell distribution and growth, as well as high rates of transfection, cell recovery and cell viability. Designed to produce linear scalability, this same substrate technology is used across bioreactor sizes from 1 m2 to 1,000 m2.
Another customer pain point that the development process addressed is the desire for flexibility—the ability to support multiple vector types and cell types, including the ability to harvest viable stem cells, for example. The harvest capability is also useful for seed train applications.
Customer collaboration, along with Corning’s experience and knowledge of materials science and cell biology has been vital to creating this sophisticated cell culture system and will continue to be integral to the final development of the larger scale Ascent Pilot and Production systems to be introduced in 2023.
Why does this approach work so well for Corning? It comes down to culture. Corning has a long history of innovation resulting from its investment in R&D and close relationships with customers. The organization remains committed to continuous innovation and prioritizing our close customer relationships. This is what enables this type of incubator environment to function successfully.
Corning has been a leader in cell culture for nearly a century. We understand the nuanced nature of various cell types and their different requirements. Moreover, as a material science-based company, we understand how to utilize the unique properties of materials to meet specific needs. All of this has coalesced to enable the engineering of novel product designs to support scale-up of adherent cell culture while maintaining an ideal environment for cell growth, functionality, and productivity. Corning’s broad knowledge base and depth of experience in R&D and manufacturing, covering a variety of industries — combined with the passion to enable life-changing medical breakthroughs — is key to our success.
