Cell Culture Dish Podcast

As demand for DNA and RNA therapeutics continues to accelerate, manufacturers are under increasing pressure to improve efficiency, reduce risk, and scale production without expanding facility footprints. One emerging solution is the integration of traditionally separate downstream steps into a single automated platform. Asahi Kasei Bioprocess, has addressed this need with the THESYS® platform, a suite of oligonucleotide manufacturing technologies designed to streamline workflows from synthesis through downstream processing. In a recent podcast, Sagar Bhatt, Senior Project Engineer at Asahi Kasei Bioprocess America, discussed the development of an integrated system within the THESYS C&D/TFF system combines cleavage, deprotection (C&D), and tangential flow filtration (TFF), and why this shift represents a meaningful evolution in oligonucleotide manufacturing. Rethinking a Fragmented Workflow Historically, oligonucleotide production has relied on a series of disconnected unit operations. Cleavage, deprotection, ultrafiltration, and diafiltration are often performed across multiple systems, sometimes even in different rooms. “Cleavage and deprotection are often carried out using fairly basic setups… and in many cases, they still involve a lot of manual handling,” Sagar explained. “They also typically require additional equipment, like separate tanks, which adds complexity to the process.” This fragmented approach introduces several challenges. Material transfers between systems increase processing time and create opportunities for product loss. In addition, deprotection reactions, particularly for RNA, require careful thermal control due to heat generated during acid addition. “If the rate of the acid addition and resulting temperature rise are not controlled carefully, it can negatively impact the product… and damage product quality.” Facility constraints add another layer of complexity. Because oligonucleotide processing often involves flammable solvents, operations must occur in hazardous environments. However, traditional filtration systems are not typically designed for these conditions, forcing manufacturers to physically move material between areas. Recognizing these inefficiencies, Sagar and his team saw an opportunity to simplify. “By integrating these operations into a single physical equipment and related automation, we could potentially streamline the workflow, reduce handling steps, and significantly improve overall manufacturing efficiency.” From Concept to THESYS® Integration The idea of combining reaction-based and membrane-based processes might seem complex, but Bhatt emphasized that the separation of these steps is largely historical, not technical. “Cleavage and deprotection are reaction steps… whereas TFF is a membrane separation process,” he said. “Though there are different mechanisms involved, they can operate on the same product stream and can share the same fluid handling architecture if designed properly.” Within the THESYS® platform, this integration is enabled through automation and system design that bring multiple unit operations into a single, cohesive workflow. Advances such as closed-loop temperature control, precise dosing, and real-time pressure monitoring allow both reaction and filtration steps to be managed within one system boundary. Equally important was designing the platform for hazardous environments from the outset. “That eliminated the need for intermediate product transfers, which made this integration approach much more practical.” Engineering for Efficiency and Scale One of the most significant engineering challenges was balancing performance with practicality. “Designing the combined system to keep the footprint to a minimum while also taking operability and maintainability into consideration was one of the biggest challenges,” Sagar said. The team also focused on minimizing holdup volume, maximizing product recovery, and ensuring cleanability for GMP operations—all within a compact system design aligned with THESYS®’s broader focus on efficient, scalable manufacturing systems. The result is a platform that delivers efficiency gains primarily by eliminating transfers. “In traditional setups, the material moves between different systems and sometimes even between different rooms,” he explained. “Each transfer adds time, manual handling, and potential product loss.” By consolidating operations into a single THESYS-based system, manufacturers can complete processes sequentially without interruption, reducing both time and risk. Improvements in Safety and Process Control Beyond efficiency, integration significantly enhances safety and control. “Operators no longer need to move material between systems in solvent handling environments,” Sagar said. “Keeping everything inside one enclosed physical system significantly reduces exposure risk and handling errors.” From a control standpoint, a unified automation framework governs all stages of the process. “The same system carefully controls dosing and temperature during the reaction phase and also controls pressure and flow during filtration,” he noted. “The unified control improves reproducibility and helps contain the process within validated operating conditions.” Footprint and Operational Savings The benefits extend to facility design as well. “Instead of installing separate systems with their own vessels, pumps, and control panels, manufacturers operate one integrated system,” Sagar said. “This can free up valuable clean room space and reduce infrastructure requirements.” Fewer systems also mean fewer cleaning cycles, fewer validations, and less maintenance, resulting in meaningful operational savings over time. Designing for Flexibility: A “Built for You” Approach A defining characteristic of the THESYS® platform is its flexibility. The system is designed to align with each customer’s process rather than enforce a rigid standard. “The system is designed to adapt to each customer’s manufacturing process rather than forcing the customers to adapt their processes to the equipment,” Sagar explained. For example, the system can accommodate different filtration control strategies. “Some customers perform filtration using transmembrane pressure… while others use permeate flow. The system has the capability to operate on both.” Customer feedback also shaped physical design elements, including vessel sizing, filter configurations, and facility integration. “These kinds of small but critical considerations help the system fit naturally into the customer’s manufacturing environment without major disruptions.” Validation, Compliance, and Integration Integration also simplifies GMP validation. “When you combine multiple operations into a single system, you reduce the number of vessels, process flow paths, and connection points,” Bhatt said. “That means fewer product contact surfaces to clean and validate.” The system uses hygienic design principles and recipe-driven automated cleaning cycles, with electronic batch records supporting compliance. Importantly, the THESYS®-based system integrates easily into existing manufacturing lines. “The upstream synthesis process does not change,” Sagar noted. “After synthesis, the product simply enters this integrated platform.” Because the system is designed for hazardous environments, it can be installed directly where cleavage and deprotection already occur, eliminating the need for downstream relocation. Industry Recognition and Future Impact The system’s impact has already been recognized with an Interphex Innovation Award, which Sagar described as “a strong validation from the industry.” “The award recognized that integrating these steps… addresses real challenges that manufacturers face, like complex workflows and inefficient equipment setups.” Looking ahead, he sees integration—central to platforms like THESYS®—becoming a core design principle in oligonucleotide manufacturing. “As demand for DNA and RNA therapeutics continues to grow, manufacturers will need equipment that supports higher throughput, consistent product quality, and faster batch turnaround.” Integrated, modular platforms will play a key role in meeting these demands. “Over time, we are likely to see more compact automated systems performing multiple process steps… helping facilities scale production more efficiently and accelerate the development of new therapies.” A Shift Toward Smarter Manufacturing The integration of cleavage, deprotection, and TFF within platforms like THESYS® represents more than just a technical advancement, it signals a broader shift toward streamlined, automated, and modular biomanufacturing. By reducing complexity, improving safety, and enabling scalability, integrated systems are poised to redefine how oligonucleotides are produced, bringing the industry closer to faster, more efficient delivery of next-generation therapeutics. To learn more, please see Optimize Your Oligo Manufacturing

In this podcast, we spoke with Troy Ostreng, Senior Product Manager and David Burdge, Director of Cell and Gene Therapy at CPC about the development of the MicroCNX® aseptic micro-connectors and how they’re helping biopharma teams streamline closed-system operations for cell and gene therapies. What unfolded was a detailed and forward-looking conversation that touched on CPC’s 47-year legacy, the technical demands of advanced therapies, and the company’s plans to drive the future of automation and sterility in manufacturing. A Legacy That Positioned CPC for Today’s Advanced Therapy Boom When asked how CPC’s long history in biologics and hospital environments prepared the company for today’s cell and gene therapy landscape, David took us back to CPC’s roots. “CPC was founded in 1978, so that’s 47 years of innovation within connection technologies,” he said. “The first biologic was released in 1982, synthetic insulin, and we were there supporting the industry with open-format connectors on single-use bags.” From the early development of biologics through the shift to single-use and the rise of stainless-steel/single-use hybrid systems, CPC continuously evolved its connection technologies. They launched steam-through connectors as bioprocessing grew more complex, released their first aseptic connector in 2009, and introduced their first connector specifically targeted for the cell and gene therapy market in 2017. David explained how that history matters today: “Biologics has about a 35-year head start on advanced therapies. So the question becomes, what lessons can we transfer from biologics to cell and gene therapy as that industry grows at three to four times the rate biologics did in its first decade?” That perspective, combining biological manufacturing experience with the needs of new therapy modalities, forms the foundation for CPC’s MicroCNX platform. MicroCNX: The First Aseptic Connector Built for Small-Format Tubing As cell and gene therapy developers began scaling up manufacturing, they quickly discovered a problem: the connectors used for biologics were not designed for small-volume, patient-specific therapies. Troy described it plainly: “Several years ago, we started hearing rumblings that current connectors weren’t meeting what cell and gene therapy required.” CPC responded with a deep Voice of Customer (VOC) initiative, interviewing process engineers, operators, manufacturing leaders, and platform developers. Over and over, the same needs emerged. Operators wanted something simple. “Ease of use was the number one requirement,” Troy said. “Operators needed a product that was easy to use so they could make sterile connections in a short amount of time.” Processes demanded robustness. “Customers needed a connection they could trust—no contamination, no failures, no weak spots in the connection process,” he added. Small-volume precise applications required connectors actually designed for them. With autologous therapies, he noted, “We aren’t talking about 1,000 liters; we’re talking about 250 milliliters. And if there’s a mishap, that could mean the difference between life and death for a patient.” All of this laid the groundwork for MicroCNX, which became the first aseptic connector engineered for small-format tubing. The “Pinch-Click-Pull” Process: Sterility Meets Speed One of the standout features of MicroCNX is its elegantly simple pinch-click-pull operation. Troy explained how simplicity came directly from user feedback. “As operators walked us through their pain points, what they needed was clear: a connector they could learn immediately. So MicroCNX has a three-step process—pinch, click, pull. You can literally do it as fast as I say it.” He continued,“Once someone does it one time, they’re basically an expert. That ease of use dramatically reduces operator error.” For an industry where operator variability remains one of the biggest sources of risk and batch loss, eliminating complexity is critical. Cryogenic Challenges Call for Cryo-Rated Solutions As the conversation shifted to cryopreservation, a critical component of cell therapy manufacturing,Troy introduced the MicroCNX® ULT and MicroCNX® Nano variants. “These were really developed because therapies were being frozen to –150°C, even –190°C. You need a connector that can be frozen to those temperatures, thawed, and still be as robust as it was before.” The ULT and Nano were engineered with: Low-profile geometries to fit inside freezing cassettes Specialized materials to withstand thermal stress Chemical compatibility with DMSO and other cryoprotectants Enhanced durability to survive impacts while frozen Troy emphasized how critical it was to get the materials right: “We searched extensively for a material that could handle those harsh chemicals and temperatures. What we landed on was PPSU—polyphenylsulfone. It’s chemically sound, and it’s incredibly impact-resistant at very low temperatures.” CPC built these connectors because customers repeatedly told them: existing solutions were cracking, leaking, or becoming brittle. MicroCNX was engineered to overcome all of that. True Closed Systems vs. Functionally Closed Systems: Why the Difference Matters A substantial part of the conversation focused on the differences between closed, functionally closed, and open systems—distinctions that are often overlooked but critically important. Troy broke down the differences clearly: “An open system is exposed at some point. A functionally closed system is inherently open but gets closed temporarily to let fluid transfer. In comparison, a closed system is never open at any point.” Examples of functionally closed systems include: Biosafety cabinets (BSCs) Luer-based connections Closed system transfer devices These approaches require: Sanitization Careful environmental controls Operator expertise And, as Troy noted, “a mishap in one of these can mean losing a very valuable therapy.” CPC’s sterile connectors—including MicroCNX minimize these risks: “Our connectors allow the system to remain closed 100% of the time. That greatly reduces contamination risk.” This distinction isn’t merely academic—it has direct regulatory implications as well. David added,“In Annex 1, they refer to intrinsically sterile connection devices—like sterile connectors and tube welders—that allow operations normally requiring Grade A or B to occur in a Grade C or D environment.” That ability to operate safely in lower-grade spaces is increasingly critical as the industry tries to overcome facility and labor bottlenecks. Why Teams Are Moving Away from Tube Welding Tube welding has been part of bioprocessing for decades, but David explained why its era may be ending for CGT. “Tube welding was born out of the blood banking industry when no other solution existed. But sterile connectors don’t require capital investment. They’re faster. They eliminate issues like tubing alignment or pinhole leaks. They’re simply more reliable.” As biologics manufacturers have already done, CGT teams are now transitioning toward connectors like MicroCNX® that provide sterile, consistent, low-burden operations. The MicroCNX® Luer Variant: Supporting Transitional Workflows Not all workflows are ready to move away from luer-based devices. That’s where the MicroCNX Luer variant fits in. Troy described how it works.“You connect a syringe or bag with a luer inside the BSC, but then because the MicroCNX® connector itself is sterile, you can take it outside the hood and make a sterile connection elsewhere.” This capability bridges legacy workflows and fully closed systems—critical during process development, technology transfer, or when working with specific devices. Co-Development: The Heart of CPC’s Innovation Process As the conversation returned to CPC’s broader philosophy, David highlighted how important customer collaboration is. “It’s all about the customer for CPC,” he said. “We start with Voice of Customer. Our business and applications managers are out in the field understanding real applications and guiding them to the right products.” This feedback fuels CPC’s two major development tracks: Catalog product development (platforms like MicroCNX) Custom-engineered solutions for unique applications David added: “We maintain a full new product introduction roadmap. Some products will be released broadly. Others will be developed specifically for one customer. But both are driven by real application requirements.” This process ensures CPC’s products evolve in lockstep with the needs of advanced therapy teams. Looking Ahead: Designing Connectors for Robotics and Automation Toward the end of the conversation, David turned to one of CPC’s biggest focus areas: the future of automation. “The ultimate customer in this industry is the patient,” he said. “And right now we face barriers—capacity, speed, accessibility, cost. Process automation can significantly reduce those barriers.” Automation requires connectors designed not just for human hands but for robotics: Predictable geometries Features optimized for machine vision Forces and actuation steps compatible with robotic grippers Designs intended for automated loading and unloading David summarized CPC’s future direction: “We’re taking a fresh look at our connectors, reimagining them as something designed for robotic manipulation. It’s a high priority for us.” Troy echoed the sentiment: “Our connectors are awesomely designed for humans. But automation is coming, and we’re focused on the features robots need.” A Future Built on Innovation and Patient Impact The interview closed with both guests reflecting on CPC’s mission. “We’re incredibly passionate about innovation and meeting the needs of our customers through thoughtful product development,” Troy said. David agreed: “Every improvement in sterile connectivity bri

Surfactants are indispensable in the production of biologics, vaccines, and cell therapies. Yet for years, they’ve posed a persistent challenge: they are notoriously difficult to monitor accurately and in real time. That challenge is now being addressed by Nirrin and its groundbreaking Atlas platform, a real-time spectroscopy solution that is reshaping how biomanufacturers measure and manage surfactants. In this episode of The Cell Culture Dish podcast, Editor Brandy Sargent spoke with Bryan Hassell, Founder and CEO of Nirrin, and Hannah Furrelle, Analytical Scientist at the company, to discuss the science behind Atlas and its implications for bioprocessing. Real-Time Data Without Compromise At the core of Atlas’s innovation is its ability to provide high-quality quantitative data in under a minute—without any sample preparation. “The real breakthrough with Atlas is speed with confidence,” explained Hassell. “Time to market for biopharma is increasingly critical, yet a lot of critical decisions still rely on data from assays that take days or even months. Atlas changes that.” Unlike traditional techniques, which often require significant sample manipulation and suffer from matrix interference, Atlas uses high-precision tunable laser spectroscopy to directly analyze samples in their native form. “What makes Atlas so powerful is that we’re looking at the sample without altering it,” Furrelle explained. “That means the data we get is true to the process—there’s no distortion from prep steps or artifacts introduced by the method.” Moving Beyond PLS: A New Modeling Approach One of the technological breakthroughs enabling this leap in performance is Nirran’s move away from PLS models in favor of an iterative optimization framework. This approach eliminates the need for extensive training data, reducing model complexity while increasing robustness and flexibility. “Where a PLS model might need 20 to 30 bioreactor runs to build a dataset, Atlas delivers data on the fly,” Hassell said. “It’s not only faster, it’s more robust, more compliant, and more versatile—especially for applications like scale-up or tech transfer, where traditional models often break down.” Applications Across the Biomanufacturing Workflow Atlas is already being integrated into real-world bioprocessing environments, including both batch and continuous manufacturing. In batch processes, manufacturers use Atlas to confirm critical parameters—like protein and excipient concentrations—before proceeding to the next unit operation. This enables earlier course corrections and helps prevent downstream failures. “In the past, you either waited days for lab results or moved forward at risk,” said Hassell. “Atlas provides the immediate answers needed to make confident decisions in the moment.” For continuous manufacturing, the value is equally profound. Atlas provides the real-time, quantitative feedback necessary for dynamic process control. “You can’t have continuous processing without real-time data,” he said. “Atlas gives you the insights needed to support real-time decisions at every step.” Eliminating Risk with No-Prep Analysis One of Atlas’s standout features is its ability to deliver no-prep analysis. This eliminates sources of variability that often arise during sample handling and processing. “We’re scanning samples in their native form,” said Furrelle. “That means what we’re measuring reflects what’s actually in the process—without distortion from dilutions or centrifugation.” This no-prep capability also speeds up workflows and eliminates risk by allowing operators to verify component concentrations instantly before committing to the next step in production. Laying the Foundation for Smart Biomanufacturing Nirrin sees Atlas not just as a data tool, but as a stepping stone to smart biomanufacturing. Although full automation isn’t yet widespread, Atlas is helping to lay the groundwork by delivering trustworthy real-time data, something most operations have historically lacked. “Right now, we’re focused on validating the technology and educating the industry,” said Hassell. “Without sensors like ours, you can’t have smart manufacturing. But once real-time data becomes available, everything else,automation, digital twins, AI,can start to fall into place.” Furrelle agreed, adding, “You can’t automate without sensors. Atlas gives you real-time insights that teams can actually use, not work around.” From QC Tool to Strategic Platform As teams adopt quality-by-design (QbD) approaches, Atlas is being used well beyond its initial QC role. It’s becoming a platform for optimizing surfactant levels, improving batch-to-batch consistency, and proactively preventing formulation issues. “You can’t have quality if you don’t start from a place of quality,” Furrelle said. “Validating components before you use them is no longer just ideal, it’s achievable.” Supporting Regulatory Compliance and GMP Readiness With growing expectations around regulatory compliance, Atlas offers distinct advantages for GMP workflows. By capturing data directly from the process, without modification, it ensures traceability, eliminates method error, and delivers reproducible results. “Getting data that wasn’t previously accessible is foundational to compliance,” said Furrelle. “Most of the time, we assume buffer concentration is correct based on scale readings and signatures. With Atlas, you can actually measure and prove it.” Hassell added that Atlas’s direct-measurement capability enhances confidence in audits and inspections. “When you can take a sample straight from the line and analyze it without modification, you eliminate layers of error. That’s critical for compliance and it’s something our customers are really gravitating toward.” Built for Sustainability and Greener Excipients Atlas also aligns with the industry’s increasing focus on sustainability. Its optical system requires no consumables, a rare feature in today’s single-use-dominated industry. “We deliberately avoided a consumables-based model,” Hassell said. “Our customers want tools that align with their long-term goals and sustainability is a big part of that.” The platform also supports real-time validation of novel excipients, including greener alternatives. Its broad spectral range is packed with chemical information, enabling confident measurement of even chemically distinct surfactants. “We’ve had great success supporting teams developing new excipients,” said Hassell. “The system’s flexibility and depth of information make it future-proof.” Real-World Impact: Surfacing Hidden Issues Early use cases illustrate the power of the platform. In one of the first beta tests, a biopharma team used Atlas to trace a suspected surfactant stability issue. “They didn’t know where the problem started, but within minutes, we helped them pinpoint exactly where the formulation went off track,” said Hassell. “It was a powerful example of real-time debugging.” Furrelle recalled a similarly impactful use case involving ultrafiltration and diafiltration (UF/DF). “Traditionally, you wouldn’t know if you lost or enriched an analyte until after the step was complete. Atlas allows you to monitor the process live and optimize it. That’s a huge advance.” A Broader Role in Process Development With increasing adoption, Atlas is quickly evolving into a comprehensive process platform. “I’ve always thought of it as more than QC,” said Furrelle. “It’s helping teams move from retrospective quality control to proactive process design.” More teams are now asking not just whether a step worked, but how to improve it. Atlas provides the data needed to make those decisions in real time. What’s Next for Nirrin and Atlas As of now, Nirrin is focused on validating the technology and supporting its integration into real-world workflows. With backing from the NIH and a growing customer base, the company has no shortage of momentum. While the current focus is on protein-based therapeutics, Nirrin is already preparing for broader applications. “We have line of sight into other modalities, like cell and gene therapies,” said Hassell. “But first, we want to solve the problems in front of us really well and help the industry move forward with confidence.” Looking Ahead: The Future of Surfactant Analytics Both Hassell and Furrelle are confident that Atlas will play a central role in the future of surfactant monitoring. “We want Atlas to be the go-to instrument for companies developing new formulations,” said Hassell. Furrelle emphasized the importance of robust analytics during tech transfer. “Right now, that hand off is often based on assumptions and broad specs. With Atlas, you can measure exactly what’s happening and that changes everything.” Conclusion Atlas isn’t just solving an old problem, it’s setting a new standard. With its speed, accuracy, and no-prep design, it’s enabling smarter biomanufacturing, better compliance, and more sustainable practices. As the industry moves forward, Atlas stands poised to become an essential platform for quality, innovation, and transformation in bioprocessing. See Atlas in Action: https://www.nirrin.tech/nirrin-atlas-evaluation-contact-us/

In this podcast, we spoke with Nainesh Shah, Sr. Application Engineer, Asahi Kasei Bioprocess America, about how inline buffer formulation and their MOTIV® system offers a more efficient, scalable, and cost-effective approach to buffer preparation. Traditional methods require large storage spaces, pose risks of leakage, and create inefficiencies that can disrupt production. In contrast, inline buffer formulation enables real-time mixing of concentrated ingredients, eliminating storage constraints and allowing for dynamic adjustments based on demand. With benefits like reduced waste, lower costs, and improved regulatory compliance, this technology is streamlining operations while ensuring precision and adaptability. As the industry shifts toward smarter manufacturing solutions, inline buffer formulation is paving the way for the future of pharmaceutical production. How Inline Buffer Formulation is Changing the Industry Nainesh, who has over 40 years in the pharmaceutical industry and six years at Asahi Kasei, highlights the evolution of buffer preparation. "Traditionally, buffer dilution involved a concentrate formulated in advance, which was then diluted with water to achieve the desired solution.” Modern inline buffer formulation transforms this process by enabling real-time mixing of individual components. "Instead of storing pre-made buffer solutions, MOTIV allows for real-time formulation using individual components. The system precisely combines these ingredients on demand, ensuring accuracy and eliminating storage-related inefficiencies," Shah explains. Enhanced Efficiency, Cost Savings, and Waste Reduction The advantages of MOTIV extend beyond storage and formulation flexibility. "With traditional methods, production can be delayed if pre-made buffers aren’t readily available. If a change in concentration or formulation is required, additional time is needed for sourcing and preparation," Shah notes. "With MOTIV, you can use a single concentrated solution to create multiple buffer variants by adjusting the dilution ratio. This eliminates the need for multiple pre-concentrated stocks, reducing storage space, waste and increasing efficiency." Cost efficiency is another crucial factor. "Return on investment (ROI) depends on whether the facility has an existing buffer preparation setup or is installing a fresh system. For existing setups, ROI typically takes around two years due to transition considerations. However, for new installations, ROI can be achieved within 1.5 years," Shah states. He adds that Asahi Kasei provides an easy-to-use ROI calculator to help companies assess their financial benefits. Additionally, inline buffer formulation improves sustainability by minimizing waste and reducing the environmental impact of excess buffer storage. By eliminating the need for large buffer stockpiles, facilities can lower their material costs and optimize resource utilization. Scalability and Customization for Diverse Production Needs One of the standout advantages of the MOTIV inline buffer formulation system is its scalability. "Our smallest system supports up to 1,200 liters per hour with three inlets—one for water and two for concentrates like acid, base, or salt solutions. On the higher end, we can scale up to 5,000 or even 12,000 liters per hour, completely customizable with multiple inlets based on customer requirements," says Shah. This flexibility is particularly valuable for pharmaceutical manufacturers with varying production demands. Facilities producing multiple types of buffers can benefit from the system’s adaptability, allowing them to switch formulations with minimal downtime. Instead of maintaining separate storage tanks for different buffer types, inline buffer formulation enables dynamic adjustments based on real-time requirements. Addressing Complex Formulations and Space Constraints MOTIV is particularly beneficial for high-volume buffer requirements and complex formulations. "As pharmaceutical processes advance, buffers require multiple ingredients, not just simple acid-base-salt combinations. MOTIV automates these complex formulations with precision, ensuring consistency while reducing human error," says Shah. Moreover, these systems help optimize space usage. Traditional buffer preparation requires large storage tanks, which can be a logistical challenge for facilities with limited space. By replacing bulky storage units with a compact inline formulation system, pharmaceutical companies can free up valuable floor space for other critical operations, leading to improved overall facility efficiency. Streamlining Global Operations and Regulatory Compliance MOTIV enables pharmaceutical companies to streamline global operations. "A single facility’s buffer formulation data can be easily transferred to other locations, reducing the need for redundant validation and documentation. This simplifies global production expansion while maintaining quality and compliance," says Shah. The ability to standardize buffer preparation across multiple facilities also aids in regulatory compliance. Pharmaceutical companies must adhere to stringent guidelines set by agencies such as the FDA and EMA. Inline buffer formulation ensures consistent production parameters, reducing variability and ensuring that each batch meets regulatory standards. By integrating real-time monitoring and control systems, manufacturers can also enhance traceability and data integrity, which are essential for compliance. Overcoming Misconceptions and Ensuring Adaptability Shah also addresses common misconceptions about inline buffer formulation. "Some worry that once the system is set up for a specific product, it can't accommodate new formulations. However, as long as the flow capacity and analytical requirements remain compatible, new buffers can be integrated seamlessly. Even additional analytical technologies can be incorporated if planned ahead." Another concern among industry professionals is whether inline buffer formulation can maintain the same level of accuracy as traditional methods. Shah assures that modern inline systems are equipped with precise monitoring technology to ensure consistency. Real-time adjustments can be made to maintain optimal formulation parameters, eliminating the risk of deviations. The Future of Buffer Preparation: Embracing Innovation Asahi Kasei’s MOTIV system is setting a new standard in buffer preparation. As pharmaceutical manufacturing continues to evolve, adopting innovative solutions like inline buffer formulation is becoming essential. By offering flexibility, cost savings, and process optimization, inline buffer formulation provides a robust solution for modern pharmaceutical production. "The industry is shifting towards efficiency and adaptability. With advanced inline buffer formulation, companies can future-proof their operations while ensuring consistent quality and regulatory compliance," Shah concludes. In an era where precision and efficiency are paramount, inline buffer formulation stands out as a transformative technology. As industries evolve, solutions like these ensure that production remains agile, scalable, and ready to meet the demands of the future. Upgrade to Better Buffer Management: Inline Buffer Formulation Systems | MOTIV®

In this podcast, we spoke with Dr. Jorge Escobar Ivirico, Product Manager, Bioprocess Solutions at Eppendorf, about the fascinating world of induced pluripotent stem cells (iPSCs), exploring their groundbreaking potential in regenerative medicine, personalized therapies, and drug development. Our guest explained how iPSCs, created by reprogramming adult somatic cells, can differentiate into virtually any cell type, making them invaluable for research and therapeutic applications. We delved into the importance of consistency, quality control, and reproducibility in iPSC production, alongside the challenges of culturing these cells, such as maintaining pluripotency and scaling production for clinical use. The discussion highlighted exciting advancements, including the development of organoids and universal T cells, as well as the ethical considerations distinguishing iPSCs from embryonic stem cells. Looking to the future, Jorge envisioned iPSCs becoming a cornerstone of standard medical practice, while acknowledging the need to address safety, scalability, and regulatory hurdles to fully realize their potential. What are Induced Pluripotent Stem Cells (iPSCs)? "Induced pluripotent stem cells are a type of stem cell created by reprogramming adult somatic cells, like skin or blood cells, back into an embryonic-like state," explains Jorge. This process involves introducing specific transcription factors, often called Yamanaka factors, to transform these cells into a versatile state. Once reprogrammed, iPSCs can differentiate into almost any cell type, making them invaluable tools for research, drug development, and potentially life-changing therapies. The Growing Importance of iPSCs iPSCs offer a range of advantages, particularly their ability to sidestep ethical concerns tied to embryonic stem cell use. “What makes iPSCs so important today,” Jorge notes, “is their versatility and potential applications. Researchers can create patient-specific cell lines, which are essential for drug screening, disease modeling, and personalized medicine.” This technology is pivotal for regenerative medicine, offering hope for repairing damaged tissues and organs. “From neurodegenerative diseases to heart damage, iPSCs open the door to innovative treatment possibilities,” he adds. Mastering the Production Process Producing iPSCs is a meticulous endeavor. "Consistency is key," emphasizes Jorge. Researchers must ensure that each batch of cells meets strict criteria to avoid unpredictable outcomes, especially when precision is vital in both research and therapeutic applications. Standardized protocols and quality control measures are essential to achieve consistency. These involve monitoring for contamination and verifying the cells' ability to differentiate into various cell types. “Imagine developing a therapy based on a specific batch of cells, only to find that subsequent batches behave differently,” he warns. “Such inconsistencies can jeopardize patient outcomes.” Tackling Challenges in Culturing iPSCs Culturing iPSCs presents its own set of challenges. High cell numbers are often needed for large-scale research or therapeutic applications, but scaling up production without compromising quality is no small feat. Maintaining the cells’ pluripotent state is another hurdle, as they can easily differentiate prematurely under certain culture conditions. "Environmental parameters like temperature, pH, oxygen levels, and nutrient availability must be rigorously controlled," Jorge explains. “Even minor fluctuations can negatively impact cell health and their ability to remain pluripotent.” Innovations Addressing Culturing Hurdles To overcome these challenges, researchers are turning to advanced techniques like 3D culture systems and bioreactors. These provide a more natural growth environment for the cells, enhancing their viability and functionality. “By transitioning from traditional 2D cultures to 3D systems, we can better mimic the natural environment, significantly improving outcomes,” Jorge shares. 3D systems also increase growth surfaces for cell attachment and allow for higher cell density, which is critical for producing the large quantities required for therapies. "It’s not just about quantity," he notes. "These systems help maintain the quality of the cells, ensuring consistent results across labs and facilities worldwide." Transformative Applications of iPSCs One of the most exciting applications of iPSCs is in creating universal T cells for therapies like CAR-T cell treatments. “Traditional CAR-T therapies require harvesting a patient’s cells and modifying them—a time-intensive process that isn’t suitable for all patients,” Jorge explains. "With iPSCs, we can create a bank of genetically modified T cells that can be used across multiple patients, reducing risks like graft-versus-host disease and speeding up treatment timelines." Balancing Potential with Risk Despite their promise, iPSCs come with risks. “If iPSCs are not fully differentiated before transplantation, they can form teratomas—tumors containing various cell types,” Jorge cautions. Prolonged culturing can also lead to genetic instability, raising concerns about mutations that could affect therapy outcomes. Additionally, advanced techniques like CRISPR gene editing, while revolutionary, carry risks of off-target effects that could lead to unintended consequences. “Ensuring the safety and efficacy of iPSC-derived therapies requires rigorous preclinical testing and long-term monitoring during clinical trials,” he emphasizes. The Role of Embryonic Stem Cells While iPSCs offer an ethical alternative, Jorge argues that embryonic stem cells still have a role in research. "They provide unique insights into early human development and serve as important controls for studying pluripotency and differentiation," he explains. "Each type of stem cell has its own advantages, and we should leverage them where they are most effective." A Glimpse into the Future Looking ahead, Jorge envisions significant advancements in iPSC-based therapies over the next 5-10 years. “We’re likely to see more approved treatments for conditions like neurodegenerative diseases, heart disease, and certain cancers,” he predicts. Improvements in manufacturing and scaling processes will make these therapies more accessible, potentially transforming them from experimental solutions to standard medical practices. Remaining Challenges Achieving these milestones will require addressing several hurdles. "Safety and standardized production protocols are critical," Jorge stresses. Regulatory frameworks also need to evolve to keep pace with these advancements. “The future of iPSCs is incredibly promising, but we must remain diligent in overcoming the scientific, logistical, and ethical challenges ahead.” The field of iPSCs continues to inspire hope for groundbreaking medical treatments, making this an exciting time in regenerative medicine and stem cell research. “iPSCs are truly a testament to human ingenuity,” Jorge concludes.

In an era where industries are increasingly driven by data and automation, the bioprocessing sector is embracing digital transformation to streamline workflows and improve productivity. However, blending the complex and highly regulated world of bioprocess with digitalization poses unique challenges. In this podcast, we talk to Dr. Simon Wieninger, Head of Portfolio and Applications at Eppendorf SE about how the journey toward digital integration requires well-defined goals, user-centered design, cross-industry learning, and, crucially, trust. Setting Clear Goals: Purpose-Driven Digitalization “Digitalization shouldn’t happen for digitalization’s sake,” Dr. Wieninger advises. While the temptation to adopt cutting-edge technology is high, each digital tool or system must serve a specific purpose. For bioprocessing organizations, establishing these objectives upfront is critical to ensure that digital investments yield meaningful results. Whether the aim is to boost productivity in production facilities, refine R&D processes, or improve operational efficiency in support functions like HR, having clearly defined goals anchors digital efforts in purpose. This intentional approach is especially significant for production and R&D sectors within bioprocessing. Here, digitalization can streamline processes such as real-time data monitoring, automated adjustments to culture environments, and improved reporting and compliance tracking. By aligning digital goals with broader business objectives, organizations can make more effective use of resources and ensure that digitalization contributes positively to organizational growth. Bridging Skill Gaps and Building Trust: Making Digital Tools Accessible A successful digital transformation relies on the people who will use these tools day-to-day. However, not everyone in bioprocessing has a background in software or programming. Simon points out that for digital tools to be effective, they must be intuitive and accessible to all team members, from scientists in the lab to technicians on the production floor. "We need to design solutions that everyone can use," he says, noting the importance of user-friendly interfaces that require minimal technical knowledge to operate. Part of building an accessible digital framework is understanding the varying comfort levels with technology within the workforce. Some employees may be tech-savvy, while others are less familiar with digital tools. Recognizing and accommodating these differences is crucial to creating a smooth transition. Moreover, as Simon explains, trust is fundamental—not only trust in digital tools but also in the partnerships with vendors and technology providers who support this transformation. Organizations should leverage the expertise of these partners, building collaborative relationships to create solutions that meet specific needs and ultimately make bioprocess workflows more efficient. Learning from Other Industries: Adopting Best Practices in Automation and Standards The bioprocess industry has much to learn from sectors like automotive, finance, and telecommunications, which have long relied on automation and standardized processes to boost efficiency. In automotive manufacturing, for instance, high levels of automation allow for the production of thousands of vehicles with minimal human intervention. Bioprocessing, by contrast, has historically been more manual and labor-intensive, particularly in R&D and small-batch production. According to Simon, one of the greatest opportunities for bioprocessing is to adopt industry standards that facilitate automation and improve interoperability across devices. One such example is the OPC (Open Platform Communications) standard, widely used in other sectors for seamless communication between devices. Applying such standards to bioprocessing could simplify data integration across lab instruments and production equipment, allowing researchers to capture and analyze critical information more efficiently. Additionally, industry leaders could set standards for digital protocols and automation practices, which would pave the way for faster digital adoption across the field. Addressing Regulatory Challenges: Transforming Compliance through Digitalization The bioprocess industry operates under stringent regulatory standards, which some view as an impediment to digital innovation. However, Simon argues that regulatory requirements shouldn’t be seen as obstacles but rather as factors that digital solutions can help address. In industries like finance and insurance, also highly regulated, companies have successfully incorporated digital tools to streamline compliance. Similarly, in bioprocessing, digital platforms could help standardize and organize the data needed for regulatory filings, potentially reducing the time and resources required for compliance. Digital solutions, including cloud-based platforms and automated data management systems, could be particularly transformative in regulatory processes. By harmonizing data and ensuring accuracy across workflows, digital tools can make compliance not only faster but more consistent. Additionally, some regulatory bodies are already engaging in discussions about how to incorporate technologies like AI and machine learning into compliance filings. Although these innovations may require time to be fully accepted, regulatory agencies are increasingly open to exploring how new technologies can support safe and efficient bioprocessing. The Power of Digital Twins: Small Steps Toward Big Goals A popular concept in many industries, "digital twins" offer exciting potential for bioprocessing. These digital replicas of physical systems enable real-time monitoring, predictive maintenance, and even scenario modeling. Yet, as Simon notes, digital twin technology is still relatively new to bioprocessing, and its implementation will require gradual steps. In the construction industry, for example, a similar concept known as BIM (Building Information Modeling) integrates all data related to a building project, from design specifications to material inventories, making it available to all stakeholders. While bioprocessing might not yet be ready for an all-encompassing digital twin platform, companies can start small—implementing digital twins for specific workflows or equipment and gradually expanding over time. This incremental approach can yield immediate benefits while setting the foundation for larger-scale digital initiatives. Embracing Cloud Technology and Real-Time Monitoring: Moving to Industry 4.0 Cloud platforms and AI have been at the forefront of Industry 4.0 for years, but only recently has the bioprocessing industry begun to fully embrace these technologies. Cloud storage allows for centralized data management, enabling teams to access information from any device, anywhere. This flexibility has profound implications for researchers and technicians, who can now monitor processes remotely. “Imagine checking on a bioreactor’s status from your phone while you’re out with your family,” Simon explains. This real-time access not only enhances convenience but also provides peace of mind to scientists who can verify that their cultures are growing as expected. AI-powered real-time monitoring and data analysis tools also have significant benefits for process efficiency and productivity. By automating data capture and analysis, these technologies enable faster decision-making and reduce the likelihood of errors. Over time, the integration of cloud-based tools and automation could lead to smarter, more efficient bioprocessing workflows. With every iteration, companies will gain a better understanding of how to refine and optimize these processes, driving the industry toward more consistent and scalable digital practices. The Future of Bioprocessing: A Hybrid of Digital and Analog Looking ahead, Simon envisions a future where bioprocessing laboratories achieve a balance between digital and analog technologies. While complete digitalization may not be feasible—or even desirable—within the next five years, incremental advances in data processing and automation will help researchers and technicians become more efficient and productive. Automation, particularly in areas like sampling, data integration, and real-time monitoring, will streamline lab work, allowing scientists to focus on research rather than routine tasks. Ultimately, the goal of digital transformation in bioprocessing is to bring life-saving therapies, such as cell and gene therapies, to market faster. By reducing time spent on data management and process optimization, digital solutions empower scientists to concentrate on breakthrough discoveries. As data standards and digital infrastructure improve, the industry may also see an increase in collaborative projects, as cloud platforms make it easier for teams from different locations, and even different companies, to share data securely. A Call to Collaboration: Sharing Knowledge for a Digital Future Closing with a call to action, Simon invites bioprocess professionals to reach out, share insights, and learn from each other’s experiences with digitalization. “Digital transformation has incredible potential to accelerate progress in the bioprocess industry, and I’m excited to be part of that journey,”. By fostering a collaborative spirit and supporting each other in the quest for effective digital solutions, bioprocess organizations can collectively improve human health outcomes and bring new treatments to the world more rapidly. In the end, bioprocessing’s journey toward digital transformation is not just about adopting new tools—it’s about building an industry that is faster, more resilient, and better equipped to meet the challenges of tomorrow.

In this podcast, we spoke with Dr. George Wang, Vice President of Discovery and Preclinical Services at WuXi Biologics about the importance of identifying potential manufacturing, stability, and scalability challenges early to mitigate risks, reduce costs, and streamline drug development timelines. By evaluating factors such as solubility, stability, and manufacturability during initial candidate screening, companies can avoid costly setbacks later in the process. Advanced tools like high-throughput assays, computational modeling, and AI-based predictions are now essential for these evaluations. What Is Developability? Dr. Wang began by defining developability as the assessment of whether a drug candidate possesses the necessary attributes to be scaled up for production during Chemistry, Manufacturing, and Controls (CMC) development and, ultimately, for clinical trials and commercialization. He explained, “It’s about identifying potential red flags early on—issues like aggregation, degradation, or manufacturing inefficiencies—that could derail a candidate further down the line.” Why Focus on Developability During Discovery? Traditionally, discovery efforts have focused on identifying antibodies with the highest efficacy and safety profiles. However, the increasing complexity of biologics, including bispecific antibodies and antibody-drug conjugates, has shifted industry focus. Dr. Wang emphasized the costly consequences of overlooking developability in the discovery phase. “Imagine investing millions into a molecule, only to discover insurmountable stability or manufacturability issues during development,” he said. “Performing these assessments early is like an insurance policy, mitigating risks and saving time and resources.” The Economic Case for Early Developability Assessments Dr. Wang highlighted the economic rationale for incorporating developability assessments during the initial discovery phase. “The cost of discovery is less than 1% of the total development cost. Spending a bit more upfront can save millions in reengineering or restarting development,” he noted. He also pointed out that superior developability attributes can provide a competitive edge, enabling faster clinical trial entry or product approval. Key Challenges and Industry Solutions Despite its benefits, the integration of developability assessments in discovery labs faces challenges. Labs often lack the tools, materials, and expertise required for systematic evaluations. “Developability attributes must be assessed using a robust combination of computational methods, analytical tools, and high-throughput assays, which many labs are not equipped to handle,” Dr. Wang explained. Companies like WuXi Biologics have stepped in to bridge this gap. “Our Discovery unit collaborates closely with our CMC team to identify and address developability issues early on,” said Dr. Wang. WuXi’s “WuXiDEEP™,” platform has become a cornerstone of their success, helping fix more than 50 problematic molecules and guiding hundreds of projects through the development pipeline. A Stepwise Approach to Developability Dr. Wang outlined a stepwise approach to developability assessments, starting with high-throughput evaluations during the initial screening of hundreds of candidates. “We use computational analysis to identify red flags such as post-translational modification hotspots or aggregation risks,” he explained. Promising candidates then undergo more detailed assessments, requiring larger material quantities and lower-throughput methods. Even when issues arise, solutions like protein engineering can salvage candidates with strong biological functions. “It’s not about discarding problem molecules outright but addressing and optimizing their developability profiles,” Dr. Wang emphasized. The Role of AI in Developability Assessments Artificial intelligence (AI) is playing an increasingly significant role in drug discovery, and Dr. Wang underscored its potential in developability assessments. “AI-based modeling and prediction tools enable us to anticipate developability challenges early, optimizing the process even further,” he said. Practical Impact and Case Studies Dr. Wang discussed the webinar he gave, Developability Assessment and Optimization in Antibody Drug Discovery, in which he shared case studies that demonstrated the transformative power of early developability assessments. From rapid decision-making to optimized engineering solutions, these examples illustrated how WuXi Biologics helps clients navigate the complex landscape of biologics development. Final Thoughts As the biologics industry continues to evolve, developability assessments have become indispensable for reducing costs, saving time, and maintaining competitive advantages. Dr. Wang’s insights underscore the importance of integrating this approach during the discovery phase, laying a strong foundation for successful drug development. To learn more, please listen to the full podcast and watch Dr. Wang’s webinar, which provides a detailed guide to implementing developability assessments. Developability Assessment and Optimization in Antibody Drug Discovery

In this podcast, we spoke with Isha Dey, Senior Scientist, Cell Biology R&D, at Thermo Fisher Scientific about the challenges researchers face in selecting appropriate cell culture conditions due to variability in cell lines, lack of standardized protocols, and inconsistent reagent quality. Thermo Fisher Scientific's new Cell Culture Select Tool was developed to address these challenges by providing specific recommendations for media, FBS, and cultureware for over 150 cell lines, backed by extensive R&D data. Understanding the Challenges in Cell Culture Selection Thermo Fisher Scientific's new Cell Culture Select Tool addresses a persistent challenge in laboratory science: identifying the appropriate cell culture conditions and selecting the right media, supplements, and reagents for different cell lines. The process is complicated by factors like cell line variability, lack of standardized protocols, and inconsistent reagent quality. These issues can introduce variability and impact experimental results, posing a challenge for scientists across labs. “Different cell lines have unique requirements,” explained Isha. “It’s challenging to pinpoint optimal culture conditions due to variability in cell line responses. Additionally, there isn’t always a standardized protocol across labs or comprehensive information on specific culturing needs. This can make it difficult to select the most appropriate media, supplements, and other materials.” Ensuring a consistent supply of high-quality products is essential for reproducibility in experiments. Thermo Fisher Scientific's trusted brands, such as Gibco, Nunc, and Invitrogen, are known for their quality, which is critical for minimizing variability in experimental readouts. The Inspiration Behind the Cell Culture Select Tool The idea for the Cell Culture Select Tool originated from an update to Thermo Fisher Scientific's online technical reference library. Previously, the website listed recommended media types segmented by cell line culture methods—adherent, semi-adherent, or suspension. While helpful, this list was lengthy and lacked interactive functionality. Isha said, “We realized that we could streamline this information into a user-friendly tool”. “In our R&D labs, we culture over 150 cell lines using various media, supplements, and equipment. By making this data accessible to other researchers through an interactive tool, we hoped to eliminate the guesswork and enable reproducible cell culture success.” The tool now provides recommendations for specific media, supplements, and cultureware for culturing, passaging, and freezing over 150 cell lines. With in-house data supporting 75% of these lines, researchers gain access to the resources and insights gathered from Thermo Fisher’s extensive R&D experience. Selecting Cell Lines for the Tool The team started with cell lines listed in their technical reference webpage and expanded the list based on the lines frequently cultured in their R&D labs. These labs conduct heavy cell culture work for various applications, including media development, fluorescence imaging, Western blotting, flow cytometry, transfection, transduction studies, and more. “We wanted to make our R&D data available to researchers for convenience,” shared Isha. “This effort involved many scientists across R&D sites who contributed data and images showing how each cell line appears in recommended media.” Quality and Verification in Thermo Fisher’s Labs The tool’s data is backed by rigorous testing in Thermo Fisher’s R&D labs. Cells are grown in their respective media, culture plastics, and consumables over multiple passages to ensure accuracy. For cancer cell lines, STR profiling and mycoplasma testing are conducted regularly, while stem cell cultures are assessed for pluripotency and purity using imaging and flow cytometry. “Representative images of cell lines, captured using our EVOS imaging system, are available in the tool to help users understand how cells should look in the recommended media,” said the spokesperson. This visual support is particularly helpful for researchers new to specific cell lines, as it aids in verifying successful cultures and maintaining reproducibility. Future Updates for the Tool Thermo Fisher plans to continuously update the tool by adding new cell lines and products as they become available. Recent updates included new products like the Gibco CultureCEPT Supplement and Nunc cultureware with Nunclon Supra surface. “The Gibco CultureCEPT Supplement, for example, reduces cellular stress and improves viability during handling and processing steps where cell damage and death could occur,” explained the representative. “Meanwhile, the Nunclon Supra Surface simplifies work with complex cell lines and primary cells by enhancing attachment and morphology.” These updates reflect Thermo Fisher’s commitment to innovation, responding to evolving research needs with products that simplify and improve cell culture work. A Collaborative Effort with Researchers in Mind The development of the Cell Culture Select Tool was a collaborative project involving many different teams at Thermo Fisher. The goal was to create a one-stop solution for researchers to understand cell culture requirements for any cell line, offering a resource that combines convenience and scientific rigor. “We hope that researchers around the world find this tool useful,” the Thermo Fisher spokesperson said. “We also welcome feedback to further improve the tool and ensure it continues to meet researchers’ needs.” The Cell Culture Select Tool is available at thermofisher.com/cellcultureselect, where researchers can explore its features and contribute feedback for future enhancements. Conclusion Thermo Fisher’s Cell Culture Select Tool represents a significant advancement for researchers in the field, combining the company’s R&D expertise with an easy-to-use, interactive format. By addressing the challenges of cell culture variability and consistency, Thermo Fisher is enabling more reproducible research and helping scientists achieve better outcomes in their work. To try the Cell Culture Select Tool for yourself, please see thermofisher.com/cellcultureselect

In this podcast, we spoke with Ryan Bernhardt, CEO of Biosero and Jesse Mulcahy, Director and Head of Automation at Cellino about the importance of utilizing automation in cell therapy research and production and the potential of these technologies to transform the healthcare landscape and improve patient access. The Challenge of Accessibility in Cellular Therapy The traditional methods of creating induced pluripotent stem cells (iPSCs) are notoriously laborious and expensive, often costing hundreds of thousands, if not millions, of dollars per patient. This high cost poses a substantial barrier to accessibility for many patients in need of personalized cell therapy treatments. Cellino is leveraging advanced automation, AI, and linear technology to dramatically redefine and improve on traditional production processes. Advancing Automation in Cell Therapy Cellino’s approach employs its innovative technology, known as NEBULA. This system utilizes self-contained units, referred to as cassettes, to cultivate personalized cell therapies directly in hospitals. NEBULA uses AI to monitor cell growth while incorporating laser technology to selectively eliminate unhealthy cells. This level of automation has the potential to reduce the manufacturing costs of personalized stem cell therapies by at least tenfold, making treatments more accessible to a broader range of patients. Supporting automation for Cellino is Biosero’s Green Button Go software suite, which plays a crucial role in automating the workflows of life science organizations. Ryan explained how their technology empowers life science organizations to automate essential scientific processes, facilitating the scheduling of workflows and direct communication with lab instruments. With the capability to run processes continuously—day or night—labs can maintain and cultivate cells without the constraints of a conventional workweek. This 24/7 operational capacity allows for the rigorous demands of cellular therapeutics to be met more efficiently. Bridging Gaps with Integrated Automation Ryan describes how lab automation can no longer be seen as merely robotic arms and conveyor belts; it integrates three key elements: physical, logical, and data. By orchestrating these components, automation streamlines and accelerates research across labs that were traditionally siloed and specialized in specific areas. This approach connects different labs, unifying knowledge, expertise, and data systems, enabling real-time decision-making and data-driven insights. Automation enhances workflows by eliminating delays and optimizing project timelines. It serves as a performance tool for scientists, improving efficiency, consistency, and the ability to address complex challenges, while also incorporating AI and machine learning for smarter, continuous processes. Jesse Mulcahy, Director and Head of Automation at Cellino emphasized the significance of Biosero’s orchestration software in improving efficiency by optimizing scheduling, reducing downtime, and maximizing throughput in cell therapy production. The Green Button Go orchestrator improves consistency by automating key steps and minimizing human intervention, ensuring reproducible results for quality control. The software is flexible and modular, allowing for easy adaptation of workflows as needs evolve, whether adding new instruments or changing protocols. This scalability is crucial for producing personalized cell therapies more efficiently and at a larger scale. Addressing Pain Points and Future Trends Despite the advancements, there are still hurdles to overcome in the biologics’ development landscape. Ryan notes that the field is evolving rapidly, with significant advancements in cell culturing, automation, and decision-making processes. Traditional cell culturing is being automated to assess key factors like cell viability, confluence, and other qualitative aspects, aiding decisions on feeding, splitting, and harvesting. While improvements are still needed, especially for various cell lines and techniques, the integration of cryopreservation and storage/retrieval is also advancing. Newer technologies like spheroids, organoids, and gene/protein therapies are driving automation efforts, with a focus on achieving robustness, cost-effectiveness, and higher quality outputs in life science organizations. Looking ahead, both Ryan and Jesse envision a future of enhanced modularity and integration of AI in biologics development. As more laboratories adopt decentralized manufacturing systems, the potential for on-site production of personalized therapies will drastically reduce costs and time associated with transporting and scaling these treatments. The integration of advanced imaging and robotics technologies will also allow for unprecedented precision in monitoring and manipulating cells, opening new avenues in cell and gene therapy. A Bright Future for Automation in Biologics The future of automation in biologics development appears promising, with the potential to transform the industry and enhance patient access to innovative therapies. Ryan’s parting words capture the excitement of this new era: “It’s hard to think about science being done in the absence of automation.” Meanwhile, Jesse advises organizations to approach automation strategically, starting small and focusing on areas that promise immediate benefits while ensuring team involvement to facilitate smooth transitions. As these technologies continue to evolve, the collaboration between companies like Cellino and Biosero will be pivotal in shaping the future of healthcare, making groundbreaking treatments more accessible to patients in need. To learn more, please see: Cellino's website at https://www.cellinobio.com/ Biosero's website at https://biosero.com/

In this podcast, we spoke with Fran Gregory, Vice President of Emerging Therapies at Cardinal Health about the cell and gene therapy landscape, innovative solutions to reduce cost, the regulatory environment, and reimbursement. Fran Gregory brings extensive experience in the biologic drug sector. As a pharmacist, she has worked across various areas, including payer PBM, pharmaceutical manufacturing, and now at Cardinal Health. Gregory oversees the advanced therapy solutions and biosimilars business units, which focus on cell and gene therapies and cost-saving biologics, respectively. Cell and Gene Therapy Landscape In the cell and gene therapy landscape, there are about 25 FDA-approved products in the U.S., split into 35% cell therapies and 65% gene therapies (at the time of the interview, now 38). This field has rapidly evolved since the approval of the first CAR-T cell therapies in 2017, and the FDA continues to support innovation, with a pipeline of around 1,500 products under development. The agency aims to approve over 100 products by 2030, potentially benefiting more than 100,000 patients. Therapeutic areas include oncology, hematology, neurology, diabetes, and even conditions affecting vision and hearing. Gregory notes the unique challenges in this field, such as conducting clinical trials with small patient populations, complex manufacturing processes, and stringent cold chain logistics for distribution. The high cost of these therapies also poses a challenge, as some treatments can cost millions. However, opportunities abound as the healthcare system innovates to improve regulatory processes, distribution methods, and patient experiences. Reducing Cost She explains that the high cost of cell and gene therapies is due to the intensive research, development, and manufacturing requirements, particularly for treatments targeting rare diseases. Although the upfront cost is high, these therapies can offer long-term savings by reducing ongoing medical expenses for patients. New payment models, such as outcomes-based agreements, annuities, and warranties, are being developed to increase patient access and manage costs. One innovative approach is the Cell and Gene Therapy Access Model, inspired by President Biden’s 2022 executive order on lowering prescription costs. This model enables CMS to negotiate with manufacturers on behalf of states, enhancing access for patients and encouraging manufacturer participation. The first products under this model, aimed at sickle cell disease, are expected to launch in early 2025. Gregory expresses optimism about the future of these therapies and their potential to drive further healthcare innovation. Regulatory Environment The regulatory environment for cell and gene therapies is evolving quickly as the FDA is committed to expediting the market availability of these products. The agency offers pathways like accelerated approval, where manufacturers can bring products to market based on indicative clinical outcomes and continue gathering real-world evidence post-approval. The FDA’s regenerative medicine advanced therapy (RMAT) designation also addresses the small patient populations in cell and gene therapy trials, focusing less on traditional statistical significance. Looking ahead, the FDA will increasingly emphasize outcome measures and closely monitor manufacturing processes to ensure safety and efficiency as technologies evolve. Reimbursement Organizations like the Institute for Clinical and Economic Review (ICER) will also play a significant role in evaluating both clinical and economic outcomes, influencing pricing and reimbursement discussions between manufacturers, governments, and insurers. As the landscape grows, these evaluations will guide not only regulatory decisions but also payment models, ensuring that gene therapies offer value and affordability. Cardinal Health is deeply involved in the commercialization of cell and gene therapies, providing end-to-end support from regulatory consulting and market access preparation to logistics and patient services. The company assists manufacturers with FDA processes and market readiness, including payer and provider engagement well before a product’s launch. Cardinal Health’s expertise in distribution, particularly with cold storage and just-in-time delivery, ensures that products reach the right place at the right time. They also offer financial risk management and patient support services, including benefits verification and travel logistics, ensuring that patients can access and adhere to their treatments seamlessly. Biosimilars In the biosimilars space, there are currently over 50 FDA-approved biosimilars (at the time of the interview, now 60), with a pipeline promising even more competition in coming years. Biosimilars are expected to deliver significant healthcare savings, estimated to reach over $180 billion by 2027. Cardinal Health emphasizes that optimizing the adoption of biosimilars is essential for reallocating resources to fund new, innovative therapies. Uptake has been strong in oncology but slower in other areas like immunology, mainly due to provider education gaps and pharmacy benefit manager (PBM) formularies. Cardinal Health works to influence biosimilar adoption through provider and patient education, streamlining processes, and addressing regulatory complexities unique to the U.S. market, such as the interchangeability designation. The organization emphasizes the importance of PBM placement of biosimilars on formularies and the removal of reference products to accelerate adoption. By simplifying processes and ensuring healthcare providers understand biosimilars, Cardinal Health aims to expand access, reduce costs, and create opportunities for more innovative treatments. The biosimilar adoption is crucial for the healthcare ecosystem as it offers a rare opportunity to reduce costs, especially in biologics. By leveraging biosimilars, the healthcare system can reinvest savings into groundbreaking treatments like cell and gene therapies, ultimately improving patient access and outcomes while managing the economic burden. In summary, optimizing biosimilar use and integrating innovative gene therapies are pivotal to the future of healthcare. Cardinal Health is positioned to facilitate both, ensuring the healthcare system remains sustainable and capable of accommodating new treatments as they emerge.