Cell Culture Dish Podcast: Recent Episodes
Brandy Sargent
The Cell Culture Dish (CCD) podcast covers areas important to the research, discovery, development, and manufacture of disease and biologic therapeutics. Key industry coverage areas include: drug discovery and development, stem cell research, cell and gene therapy, recombinant antibodies, vaccines, and emerging therapeutic modalities.
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 SelectionThermo 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 ToolThe 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 ToolThe 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 LabsThe 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,
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 TherapyThe 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 TherapyCellino’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 AutomationRyan 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 TrendsDespite 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.
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 LandscapeIn 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 CostShe 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 EnvironmentThe 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.ReimbursementOrganizations 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,
In this podcast, we spoke with Luca Alberici, Senior Vice President and General Manager, Milan Facility, AGC Biologics about the road to their recent EC and FDA approval to commercially manufacture Lenmeldy™ and their future plans in cell and gene therapy. What is Lenmeldy?We began the podcast by talking about AGC Biologics’ Milan site and their FDA approval to commercially manufacture Orchard Therapeutics’ Lenmeldy. Luca explained that Lenmeldy is a gene modified cell therapy product for the treatment of Metachromatic leukodystrophy (MLD), an ultra-rare hereditary disease characterized by accumulation of fats that causes neurodegenerative symptoms. It is a pediatric disease, and patients generally die by the age of five. With this therapy the patient’s stem cells are collected and modified through the use of a lentiviral vector to add a gene called ARSA that encodes for the right form of the enzyme that these patients are encoding wrong. These modified stem cells are then administered back to the patient so they can immune reconstitute not only the immune system, but the cells will also cross correct through secretion of the right form of the enzyme. After just a single shot of the therapy, there is an improvement in their condition and they develop normally, especially if treated in a pre-symptomatic phase. This is the power of gene therapy at its best. The Pathway to FDA Approval for Commercial ManufactureWe then discussed the pathway for receiving approval to commercially manufacture this product and how the AGC Biologics Milan team navigated this process. Luca described that it was quite a long journey. AGC Biologics were manufacturing this product at preclinical and clinical phases dating back roughly 15 years. They worked with a series of different sponsors, it was developed by the San Rafaelle Telethon Institute for Gene Therapy in Milan Italy, then GSK continued the clinical development before it was acquired by Orchard Therapeutics. AGC Biologics remained the manufacturer during this time and in 2020 received approval for commercial manufacture of the product in Europe, but FDA requirements are different so over the last two years, they partnered with Orchard Therapeutics and worked to meet the FDA requirements for approval. Luca explained that approval required a great deal of work on the process, the analytics, the quality system, supply chain, and raw materials. One of the most transversal aspects of the validation of a product is getting it ready to be manufactured for the market and it was great to go this last mile with a strong partner like Orchard Therapeutics. He also credits the infrastructure of AGC Biologics, which is a multi-site global organization and provided the Milan site great support in terms of general quality, standards, procedures, and simply by having faced multiple FDA inspections before. The combination of all these factors was what carried them to the finish line, it required extensive teamwork, not only at the Milan site but also the entire organization. The Only Site to Receive EC and FDA Commercial Manufacture ApprovalI followed up by mentioning how with approval from the European Commission and the FDA, the AGC Biologics Milan facility is the only one in the cell and gene therapy industry to have commercial manufacturing authorization from both the FDA and the EC for LVV and cells. I asked Luca why there are so few CDMO's who have achieved this and what makes the FDA and EMA approval process so challenging? He explained that the Milan site was the first site to receive clinical manufacturing approval for an ex vivo gene therapy in 2003, 21 years ago, when cell and gene therapy was almost nonexistent at the time. They were the first facility to receive approval for commercial manufacturing in Europe for a marketed product in 2015/2016, 10 years ago. Now they are the only site who can do viral vector and cell therapy, both approved from the main authorities,
This panel discussion was originally published in the eBook “ Monoclonal Antibody Manufacturing Trends, Challenges, and Analytical Solutions to Eliminate Bioprocessing Bottlenecks”You can download all the articles in the series, by downloading the eBook. Panel discussion members:Carrie Mason - Associate Director, R&D at Lonza BiologicsLaura Madia - Independent Industry ConsultantAlan Opper – Director of HaLCon Sales at RedShiftBioDavid Sloan, PhD – Senior Vice President, Life Sciences at RedShiftBioBrandy Sargent, Editor in-chief, Cell Culture Dish and Downstream Column (Moderator)In this panel discussion, we talked with industry experts about antibody process development and manufacturing. Specifically focusing on current antibody titer expectations, analytical challenges and how real time titer measurement is a game changer for bioproduction moving forward.Where is the industry at today with titer expectations and what are the best practices for measuring titer?Laura MadiaWith respect to expectations regarding titer over the years, what we’ve seen is a need for increased titerwithin the upstream development of a drug. As an industry, we have moved from the 80s where titers were closerto .2 to .5 grams per liter to the early 2000s where concentrations of titer production rose to 3 to 5 grams perliter. What we see today is a continued increase in titer concentrations, which creates a challenge to make surethat you have technologies that can accurately measure titer concentration without introducing any errors.The other thing that we have seen within the industry is the need for more data to not only understand what ishappening in the tank, but also to be able to make decisions about the product as the process is running orshortly after.Lastly, it is important to consider people and resources. It has been exacerbated by COVID, but it is difficultto find people to work within the industry and there are fewer people within a production suite. This has helpedto drive the need for online and remote monitoring and automation to make it easier to get the necessarymeasurements.David SloanTo follow up on the lack of workers, one of the things that we constantly hear from the customers we areworking with is that training employees can be a real challenge and a very time-intensive process. Technologiesthat are easier to use and require less expertise help get people up and running and minimize errors amongst newusers of a technology.Laura MadiaAs for the current best practices for measuring titer, HPLC is the gold standard. But HPLC presents somechallenges including training and HPLC requires a highly skilled person to get accurate results. There is a needfor something that is simple and easy to use when it comes to measuring titer. You will still need HPLC resultsfor approval and decisions at the end, but to be able to monitor titer throughout the process is important.What are the challenges associated with the way that titer is measured today and what can we do as an industryto improve?Laura MadiaOne of the challenges is that most of the assays available today are batch processes, so that lends itself toproviding a retrospective look and means that most people don’t run samples throughout the process. This isbecause most people save these tests until the end when they can run a batch and make it more cost effective,and it is typically a long time to result so running it during the process isn’t helpful. Systems today are morefor batch process and are not set up for at-line measurement, unless you are lucky enough to be able to have anHPLC that’s dedicated to that tank.Another challenge is speed and accuracy. Many of the techniques that are offline today are longer assaysbecause they’re running as a batch. You must wait for the entire batch, which is a long time to first result.
In this podcast, we spoke with Nainesh Shah, Senior Application Engineer at Asahi Kasei Bioprocess about buffer management including the benefits of inline buffer formulation, and single use inline buffer formulation systems. Buffer Management We started the podcast by talking about how critical buffer management is to bioprocessing. Mr. Shah discussed how buffers are required in large quantities during the biomanufacturing process and that traditionally buffers were made in large tanks, stored, and used as needed. However, now real estate in the bioprocessing industry is at a premium and companies are looking to utilize new technologies that can reduce facility footprint. For buffer management, it makes sense to create buffer on demand to reduce the footprint dedicated to buffer production in the past. Inline buffer formulation is a hot topic with companies who require a large quantity of buffer because it provides a way to create buffer on demand in a much smaller footprint. The interesting thing is that it is now also a hot topic among small R&D scale buffer users as well. Inline buffer formulation systems are ideal for users who need 200 to 500 liters of buffer at a time. The system takes the concentrate and adds clean water to provide just the right amount of buffer on demand. Another benefit of inline buffer formulation is that you can achieve a quick process changeover and move on to the next buffer formulation without spending valuable time cleaning the tank, taking samples, and readjusting the critical parameters. Recently, any new manufacturer, whether it's a large scale or small scale tends to move into this field of buffer management and operates one or two Inline Buffer Formulation (IBF) systems like the MOTIV™. They then use these systems to make all sorts of buffers needed for their various processes. The MOTIV Family of Inline Buffer Formulation SystemsNext, I asked Nainesh if he could talk a bit more about the MOTIV family of inline buffer formulation and fluid management systems that Asahi Kasei Bioprocess America (AKBA) offers. He explained how the award-winning MOTIV family has evolved into a series of inline buffer formulation systems designed to help companies move past downstream bottlenecks by driving buffer productivity. The product family includes 3-pump, 5-pump, and custom IBF configurations that can fit most any space, cost, or performance requirements. The MOTIV is a leader in buffer production with a range of scale from 4,500 liters per hour to 10 liters per minute to fit an entire range of volume requirements. He went on to say that they have added a new feature where MOTIV can fill up bags with buffer and monitor the quantity in the bag to make buffer on demand even easier. MOTIV SUThen we talked about the new MOTIV SU, a single use inline buffer formulation system, built to produce complex buffers on-demand effectively and efficiently, all from one pump head, and without the need for CIP/SIP procedures between batches. The innovative design modulates flow through control valves while simultaneously integrating buffer solutions and mixing. As with all the MOTIV systems, OCELOT System Control ensures precise blends every time, controlled by pH and conductivity feedback or flow. The MOTIV SU is perfect for a biomanufacturer who does not want to spend time with cleaning and validation. It is great for one time use as it does not require time spent in cleaning, validation, and making sure that it is free of all the contaminants and all the buffers which may be harmful for the next process. Another benefit would be if a biomanufacturer used a buffer which had a chemical or ingredient which would be problematic for other processes, and they wanted to eliminate any risk of contamination. Since the MOTIV SU has replaceable parts, which come as a pre-built unit, it is easy to replace the components and then the system is ready to run again.
In this podcast, we spoke with Margherita Neri, Director of Vector Process Development, Milan Site at AGC Biologics, Andrew Laskowski, Global Product Manager Bioreactors at Cytiva and Andreia Pedregal, Upstream Applications Specialist Manager at Cytiva about large-scale viral vector manufacturing. Our conversation included discussions around scalability, AAV (adeno-associated virus) and lentivirus production platforms, adherent culture, and next generation bioreactor improvements.I began the interview by asking Margherita about her work at AGC Biologics. She explained that as the Director of the Vector Process Development Unit, her team is responsible for process development of large scale viral vector production for gene therapy applications. Her team is also the first point of contact for new clients.Next, we talked about the types of viral vector platforms that AGC Biologics operates. Margherita described that at their Milan site, they offer AAV (adeno associated virus) and lentiviral vector production platforms in adhesion and in suspension, at 50-to-200-liter scale with expansion planned for up to 1,000 liters.I then asked her about some of the differences between adherent cell culture and suspension cell culture paths to commercial manufacturing. Margherita said that the first consideration is that most clinical trials in gene therapy have been sustained with vector produced from adherent cells, typically via processes performed using Cell Factory™ or Cell STACK®. Now that those gene therapy products are being commercialized, manufacturers need to increase scale and demonstrate comparability using a minimal comparability exercise. So, systems that allow adherent scale up are very useful in this process.Suspension processes are appealing from a scalability point of view because historically they were used for traditional protein bioproductions which can be scaled up to 20,000 – 30,000 liters. Of course, this scale still needs to be demonstrated for vector production that is performed mainly using transient transfection at 200-500 liter scale for lentivirus and between 500-to-1,000-liter maximum scale for AAV. Margherita went on to say that another important aspect in comparability between adherent and suspension systems is quality of the vector in terms of impurity profiles. She said that with adherent processes, cells are attached to the growth support, and the levels of host cell protein and cell DNA are lower when compared to suspension processes. This is very important for lentiviral vector production that is used in vivo where the requirements for impurity levels are very challenging, especially considering that for lentiviral vectors there is currently no affinity step for purification.I followed up by asking her how AGC Biologics can help customers that want to stay in adherent culture to scale up from current processes, for instance, from flatware to larger-scale production. She explained that when customers ask for a scale increase, they usually offer the iCELLis™ platform. First, they demonstrate at small scale the feasibility of the transition from flatware to the iCELLis bioreactor using the iCELLis Nano bioreactor. Using the iCELLis Nano bioreactor, AGC Biologics has developed a full upstream and downstream process that is highly representative of their process using the full-scale iCELLis bioreactor.AGC Biologics can then propose that customers use the vector produced in the iCELLis scale-down model to perform a comparability study between a clinical vector and the future commercial or large-scale vector. This comparability should be based not only on the comparison of titers, residuals, and all the CQA, but also AGC Biologics suggests performing a test of cell transduction on the target cells (i.e. CD34 or T cells) and evaluation on these cells of transfection efficiency – vector copy number, residuals and functionality.I followed up by asking Margherita about whether the iCEL...
In this podcast, we talked with Dr. Ma Sha, Head of Bioprocess Applications at Eppendorf SE about advancements and challenges in cell and gene therapy production along with solutions for scale up and transition to stirred-tank bioreactor suspension culture.We began the interview by talking about the biggest advancements in cell and gene therapy, including CAR T-cell therapy development, clinical results and FDA approvals. Another area of great advancement is induced Pluripotent Stem Cell (iPSC) Culture technique. Dr. Sha explained that it used to be very difficult to culture iPSCs until it was possible to culture iPSC suspension spheres in stirred-tank bioreactors, which was a big breakthrough in the cell and gene therapy area.I followed up by asking Dr. Sha what he sees as the major challenges in the development and production of cell and gene therapies that still need to be addressed. He said that one of the major breakthroughs has been the autologous therapies that have been approved, particularly CAR T-cell therapies. However, this has also been a major challenge, because the autologous model is not cost effective. As a result, there has been a shift toward developing allogeneic therapies and building this production model will be a major challenge moving forward. Another challenge on the manufacturing side is ensuring to follow Good Manufacturing Practice (GMP), as it has been a common request from cell and gene therapy companies.Next, I asked him about the move from 2D to 3D culture and his experiences with this transition. Dr. Sha shared that several of the projects that Eppendorf bioprocess works on start as 2D culture in flasks, it is a natural place to start for most of the cell lines since they are attachment cells. They must then be converted into suspension culture to enable 3D culture, since 2D culture significantly limits the yield and productivity. He went on to say that if you look back at the evolution of antibody production, it was important to convert production to suspension cell culture and this is also necessary for the cell and gene therapy field. Moving from 2D to 3D culture and especially utilizing stirred-tank bioreactors enables much higher yields. As it stands, the yield for cellular therapy cell production is fairly low, especially compared to the industry standard of CHO cells used for antibody production, so a lot of improvement needs to happen.We then discussed stirred-tank bioreactors and their increased use in cell and gene therapy development and production. I asked Dr. Sha what are the key factors that developers should consider when choosing stirred-tank bioreactors. He explained that stirred-tank bioreactors fit the model of allogeneic production. Autologous models are not suitable for stirred-tank bioreactors. Developer companies need to keep in mind that if they want to move to stirred tank bioreactor platform, they need the production model to be allogeneic. In addition, it is important to consider the support available with respect to scaling up and leveraging supplier experience. For example, Eppendorf bioprocess over the years has produced many application notes to help customers scale their manufacturing. They have even built model production systems in Eppendorf stirred-tank bioreactors. The program called “Scale up Assist” allows customers to skip much of the difficult calculations required to achieve reproducible yields when moving from smaller to larger vessels.Eppendorf has a very long history of working in protein-based therapeutic cell culture production and about ten years ago expanded to include cell and gene therapy. I asked Dr. Sha in his experiences, what are the most important takeaways in terms of areas that still need work and advancements on the horizon. For instance, what can we learn from protein-based therapy cell culture to apply to cell and gene therapy production? He said that he thought that allogeneic production is a great lesson learn...
In this podcast, we talked with Nathalie Dubois-Stringfellow, Senior Vice President of Product Development and Management at Sangamo about Sangamo’s work in gene therapy and the latest data on Sangamo’s gene therapy product candidate for Fabry disease.I began the interview by asking Nathalie if she could talk about Sangamo and the company’s pipeline. She explained that Sangamo is a genomic medicine company dedicated to translating groundbreaking science into medicine. Their technology includes gene therapy, genome editing, and cell therapy.Their zinc finger nucleus platform allows them to edit genes either by adding genes, deleting genes, repairing mutation, repressing the expression of the gene, or activating. It is a vast area of technology that they can apply to a variety of diseases.Using their breakthrough technology, they were the first to edit human genes, treat patients with gene edited T cells, treat patients with in vivo genome editing, and treat patients with engineered T cells.Our current clinical focus is on Fabry disease, a rare genetic disease and Hemophilia A sickle cell disease.She then described their recent clinical data on ST-920, a gene therapy product candidate for Fabry disease, that continues to be generally well-tolerated and presents sustained α-Gal A activity based on data from nine patients.She said that they were extremely excited about the result of this Phase I-II clinical trial. Fabry disease is an inherited disorder that is caused by mutation of the galactosidase alpha (GLA) genes which leads to deficient alpha-galactosidase A (α-Gal A) enzyme activity. This enzyme normally breaks down a fatty substance called globotriaosylceramide and without this enzyme this fatty substance builds up in the cells throughout the body, particularly in the skin, kidneys, heart, and nervous system.The current standard of care for Fabry disease is an intravenous infusion of the missing enzyme, the treatment being called enzyme replacement therapy or ERT. This provides a high concentration of the missing enzyme for a very short time and the treatment has to be repeated in those patient every two weeks. It's a very cumbersome infusion that can take several hours and typically needs to be done in the hospital, thus negatively impacting patient quality of life.Sangamo’s approach is a one-time therapy treatment where the gene for the missing enzyme is delivered to the liver cells of the patient, which are then acting as cell factory for producing the missing enzyme.Please listen to our full interview using the player above or download on the player using Apple podcasts, Spotify or More.
In this podcast, we talked with Dennis Hodgson and Phil Sanders from Agilitech about the benefits of single-use mixers, dealing with supply chain concerns, ensuring scalability, and tailoring a mixer to meet specific process needs.Benefits of Single-use MixersWe began the podcast by talking about the overall benefits of single-use technologies for mixing. Dennis explained that single-use mixers are very versatile and can be used to replace stainless steel vessels within the manufacturing area. Single-use mixers all have the same advantages of other single use components, such as coming fully sterile and eliminating the need to steam and clean in place.Dennis went on to say that another big advantage that single-use mixers have over stainless steel is the ability to customize. For example, a 500 L single-use mixer can be used with a virtually unlimited array of customized vessel configurations, which would include the inlet outlet, port configurations, sampling ports, vent filters, and various process analytics that can be added.Next, we talked about adoption of single-use technology for mixing and possible concerns that customers might have. Dennis shared that a big concern recently has been supply chain shortages that have created limited availability and long lead times for single-use consumables. He said that he has heard from some clients that they have had to skip planned production batches because the single use bags that they needed to process the batch were not available. Phil added that supply chain concerns have caused some of their clients to think about moving to stainless steel systems to avoid any production delays.Single-use Technologies Supply Chain ChallengesI followed up by asking what could be done to address single use supply chain issues moving forward. Dennis explained that Agilitech has the luxury of not being tied to any one supplier, so they can source from multiple vendors. This allows them the flexibility to move between vendors and load projects based on their capacity and lead times. This also allows them to make sure that they are offering competitive pricing because vendors know that they're not the sole source of a component.Ensuring Flexibility in Single-use MixingWe then talked about mixers presenting unique challenges in that they are used for a variety of applications with many different demands. I asked how Agilitech can ensure that their single-use mixer has the flexibility needed for multiple applications. Dennis explained that because Agilitech isn’t tied to a single design, they are able to have conversations with the client to customize a solution for their needs. Their main goal is to make a product that meets the needs of the individual companies and their process. Additionally, they design their systems purposefully to handle many different capabilities such as sampling, analytical measurements, weight measurements, temperature control, etc. Because they use standard control hardware, their mixing vessels can easily be integrated into existing control systems such as Delta V or Wonderware through the available Ethernet IP connection. This allows users to read and write to certain control parameters.I then asked about which options are available for customization on the single-use mixers. Dennis said that they can customize all the inlet and outlet ports with regards to port size, tubing length, connector type, etc. As far as the mixing units themselves go, they can be jacketed or not, have load cells or not, have probe analytics such as pH, conductivity, temperature, DOE, and optical density, so all those different analytical devices can be incorporated as well.Phil added that if there are specific standards within an organization, for what control systems need to be installed on these systems Agilitech is flexible with Rockwell, Delta V, Siemens, all the major platforms that customers might need.I followed up by asking about how these customizatio...
In this podcast, we spoke with Emanuel Krobath, Biopurification Specialist and Chiara Pacini, Bioprocess Specialist both with Pall Corporation about gene therapy process development including challenges and resources that are available for support. I began the discussion by asking Emanuel and Chiara to tell listeners a little bit more about their jobs and how they support gene therapy developers on the bench. Emanuel started by saying that as a bioprocess product specialist, he performs customer bench case studies at the customer site, specifically for the downstream process including vaccines, recombinant proteins, monoclonal antibodies and gene therapy products. He shared that the customers he works with are usually in preclinical or Phase I studies and he supports them from clarification to the final sterilizing grade filtration. This scale up, optimization, and technical support is offered free of charge to help customers succeed in their process development. He said that he also finds new technologies and ideas for the Pall R&D team during these visits.Chiara shared that she supports customers from bench scale studies through the manufacturing process on downstream starting from clarification to sterile filtration. She spends most of her time traveling to her customers’ laboratories or manufacturing sites to provide general support, conduct optimization studies and technical support training to find the best practice or membrane selection for their process.I then asked if they could share what are the most common questions that they get from their customers. Emanuel said that what size filter do they need for a specific product and what is the best material to use is one of the most common. Chiara said that for her it is how to intensify a process or make it more robust for clarification, TFF, chromatography, and membrane filtration.We also talked about a series of videos on Pall’s website and how these were created to help translational academics who work in gene therapy. Emanuel explained that they wanted to support academia specifically in their scale up and small-scale process development, because often in academia, the user will take the first filter that is available at their site. It is important that they understand and have the support to select the correct filter for their product, so that the process is optimized at manufacturing scale. Chiara agreed that the videos were designed to show we can support the development process not just for manufacturing scale, but also for initial bench scale studies. This and the initial optimization study that Pall performs with the customer ensures scalability to large scale processes and identifies the critical process parameters needed to reach high yield and product productivity.Next, we discussed what they like most about the work that they do. Chiara described how being a bioprocess specialist gives her the opportunity to meet the people in both large and small companies who are working on these therapeutics. She enjoys supporting the development of different molecules and gene therapies and is always updated on the latest techniques used for gene and cell therapy. Emanuel said that he enjoys traveling, which is important because visiting customers in person is a big part of his job. He added that it never gets boring since he is supporting customers as they deal with very diverse processes and challenging problems. His favorite part of the job is that basically they are doing scientific work at the frontline, and he saw this to an even larger extent during the COVID pandemic as they were involved in nearly every vaccine process development.I followed up by asking which projects that they were most proud of. Emanuel said that with the exponential growth of plasmid DNA demand, as it is either used as a template for mRNA vaccines or the molecular function for DNA vaccines, the upstream and downstream processes have not been optimized. Now,
In this podcast, we spoke with Cory Hinz, Engineering Manager at Asahi Kasei Bioprocess about the different methods that are available for liquid chromatography mobile phase solutions and the benefits of inline blending. Cory also describes how to implement binary blending feeding of a liquid chromatography process using inline blending.Liquid Chromatography Mobile Phase SolutionsI began the discussion by asking Cory if he could tell listeners about the different methods that are available for liquid chromatography mobile phase solutions. He explained that for chromatography, it's important to remember that the process and the chemistry should drive the method used. Some chromatography processes use prepared mobile phase solutions that don't require inline mixing, while others blend two or more solutions together to formulate. The mobile phase takes these blends and changes their composition over the course of the elution. Each of these methods is driven by the needs of the process.Inline BlendingNext, I asked Cory if he could tell us about the benefits of inline blending. He said that inline blending allows solutions to be prepared at their point of use, not just for chromatography processes, but any blending process. This increases the consistency of the blended solution, reduces dependency on the accuracy of raw materials, allows for real time quality assurance, and eliminates the risks and extra resources and space required for traditional tank approaches. Inline blending also adds an element of flexibility, allowing functions such as buffer preparation to become more of a utility than an additional process.Binary Blending Feeding of a Liquid Chromatography Process using Inline BlendingCory then provided details about how to implement a specific solution for binary blending feeding of a liquid chromatography process using inline blending. He explained that binary blending is the most common configuration they see for their chromatography equipment customers, because medium and high-pressure liquid chromatography require a dedicated pump to supply the pressure dictated by the process. It is important to design the binary blending at the suction side of the pump. This is done by employing two modulating control valves, one for each of the two components of the mobile phase, and ensuring sufficient supply pressure to each one.He then told us about the role that each of the valves play in creating the ideal blend. He described how the control valves do most of the heavy lifting for binary blending. The first valve controls the diluent, which will be the purified water or buffer that comprises the majority of the mobile phase blend. The second valve controls the component that is getting diluted. These valves each react to a different process parameter to achieve high accuracy.The second valve is the most intuitive, the component being diluted can have its proportion increase or decrease based on the movement of the control valve. For example, if the concentrate is below target, the valve will open to allow more concentrate through. This can be based on flow connectivity or any critical process parameter that can be measured inline.The first valve is less intuitive. It is controlled by the pressure in the system after the two streams have combined. If the blending pressure is too low, for example, the valve will open to increase that pressure.The result of this configuration is that if the two valves react to one another via the process but are not linked by a system control algorithm. This results in flexibility and accuracy and also provides a way to monitor and mitigate pump cavitation.Next I asked Cory about controlling the incoming process pressures of each of the valves. He said that in order for the binary blending scheme to work optimally, the incoming supply pressures of each stream should be controlled to prevent fluctuation that can disrupt the automatic blending control.
In this podcast, we interviewed Katie Keller, Director of Quality and Safety at Asahi Kasei Bioprocess America, about the importance of quality management and how to achieve the best possible results. Topics included the most critical elements of quality management, how to ensure the purchase of high-quality equipment, and future trends.I started the conversation by asking Katie what she thought were the most critical elements of quality management. Katie replied by saying that a holistic approach to quality is best for any organization. It used to be that the quality unit was considered responsible for product quality, making all the decisions, and driving all the improvements and that's not really the case today. She feels the most successful approach is that since quality is so important, everyone should be responsible for it. She went on to say that when all employees understand how they contribute to product and service quality and therefore customer satisfaction, there is more buy in throughout the organization. People are empowered to take responsibility for the improvement of the processes they manage, and this total quality management is achieved by clearly defining the interaction of each process to another, ensuring employees understand that, and then setting the expectation that quality is achieved from every level of the organization with everyone playing a part.I then asked Katie what should bioprocess equipment customers be looking for to ensure that they are purchasing high quality equipment? She told me that across industries, it's common for customers to search for suppliers with robust quality management systems. As a supplier, Asahi Kasei Bioprocess America (AKBA) can minimally prove this by achieving and advertising certification to ISO 9001. This shows that Asahi Kasei meets the minimum expectations for a manufacturing company to provide those quality products and services, but it really doesn't stop there. If they can show their customers that they have well designed, thorough processes that are continually improving, this naturally leads to better quality products and customers gain confidence in their ability to meet ongoing needs.I continued the discussion by asking if she could talk a bit about ISO certification and why it's an important part of their quality management system. Katie explained that ISO 9001 really is the minimum. Their customers in the pharmaceutical industry might stop and look when they see the ISO certification, but what really brings them confidence and satisfaction are the ways Asahi Kasei goes above and beyond this. For AKBA, ISO certification is not just words on a page, there is a reason why every requirement in that standard exists. Katie shared that she believes it is her job to interpret this in a way that means something to her organization, so they can not only live it but improve upon it and take the next step. She elaborated on her point by saying that it is how you build upon those minimum criteria that truly shows a customer who you are and what is important to you as an organization. This is how a company can start to build that quality culture where the employees believe in the message that customer satisfaction, both internal and external, comes first.I asked her about how these quality management systems affect the design and build of their equipment and how they have an impact beyond the quality management systems. Katie said that having ISO as a guideline is helpful for this, especially if they need to create or revamp a process. Asahi Kasei Bioprocess starts by asking what ISO requires to get a baseline and then looks at what their customers’ expectations for safety, quality, and productivity are. She explained that by keeping both these things in mind, they can create robust processes with controls or checkpoints to ensure they are satisfying all the requirements.However, that example is at the front end of creating a new process,
In this podcast we spoke with Klaus Kienle, Global Product Manager for the Mixing portfolio at Pall Corporation about the latest mixing technologies including single-use solutions, the need for increased flexibility, and a more standard vendor agnostic approach. The Role of Mixing in BiomanufacturingI started the conversation by asking Klaus if he could talk about the role that mixing plays in biomanufacturing and current challenges in this area. Klaus explained that mixing is an omnipresent process. It starts with upstream buffer media and ends in fill and finish. It is an important part of manufacturing across several modalities, including monoclonal antibodies, mRNA based vaccines, gene therapies and various other processes. Across these various applications, flexibility is key, and it is also the primary challenge for the future. He continued by saying that Pall customers have expressed that they want increased flexibility, better lead times, and less supplier dependency in the future.Advancements in MixingNext, I asked about the latest technological advancements in mixing. Klaus stated that the latest advancements are moving towards tackling the flexibility challenge, which means supplying solutions that are available with shorter lead times and are more vendor agnostic, so they fit with other vendors’ manifolds and full sets. This is consistent with the recent launch of the Allegro™ Ready Standard Solutions from Pall, which is not only limited to mixers, but also includes storage transfer sets and other segments. Pall has launched this new standard set ranging from a 30 liter mixer up to a 3000 liter mixer.I continued the discussion by asking if he could talk a little bit more about some of the additional advantages of this set of new standards. He described how these standards are ready to go, so if a customer is asking for a manifold, there is no time required to generate a drawing or waiting for pricing back, resulting in a short lead time. Pall is working towards having these standards available off the shelf, reducing lead time further with availability in the range of single digit weeks, depending on manufacturing and where the customer is located. He shared that Pall has invested $1.5 billion to increase capacity and reduce lead times.Single Use MixingI then asked him about some of the remaining challenges that exist with single use technologies. Klaus explained that one of the main challenges that the remains in single use is sustainability, especially since it consists predominantly of plastic components. However, there was a recent publication in New Biotechnology, authored by biopharmaceutical companies, “Streamlined life cycle assessment of single-use technologies in biopharmaceutical manufacture.” It makes the case that single use technology is providing better sustainability in the biopharmaceutical process because single use technology allows customers to use more intensified processes, thereby increasing the efficiency per consumable. Single use technologies also support a closed process and reduced clean room requirements resulting in lower energy requirements.This is in line with the new standard designs from Pall, where the filtered product line is fully closed and processing ready. For instance, now the powder port on these designs ensures a closed and controlled environment. This then allows bioprocessing companies to lower the cleanroom environment requirements, which translates to significant energy savings.Modular Mixing ApproachI continued our discussion by asking Klaus about a recent white paper published by Pall and Lonza, that highlighted a modular mixing approach. (need paper link) He described how a modular approach can give customers the flexibility that they are looking for to adapt to new requests, especially in the contract manufacturing organization (CMO) environment. Global CMOs are producing product for developers and as a result,
In this podcast, we spoke to Tom Watson, Group Leader, Product Management – Biotech Division, Gregor Kalinowski, Manager SLS Purification Consultants Europe, and Aude Iwaniec, R&D Bioprocessing Team Leader, all from Pall Corporation, about why high concentration mAbs are an increasingly important part of the biotech landscape, current manufacturing challenges and solutions, and future trends. High concentration drugs offer benefits for patients I began the discussion by asking why high concentration mAbs are an important topic in today’s biotech landscape. Tom explained that high concentration drugs are an important innovation because when a biotech drug can be prepared at high concentration that is administrable, it is usually self-administered in a subcutaneous mode. This method of delivery brings lifestyle benefits to patients and reduces health care costs because it negates the need for an intravenous treatment. Subcutaneous biotech drugs have been available for a while, but recently more companies are developing new drugs or formulating existing ones at high concentration. High concentration mAb manufacturing vs. more traditional mAb production I followed up by asking what some of the differences in terms of manufacturing high concentration mAbs versus more traditional mAb production are. Tom described that a mAb or recombinant protein for subcutaneous delivery is going to be prepared at a high concentration. Starting with the final concentration steps, it is common to have a highly viscous fluid of 10 to 30 centipoise, with a concentration of greater than 100 grams per liter and often higher than 250 grams per liter.
He went on to say that the concentration step reduces the volume of the fluid processed across the subsequent unit operations that are typical of a biotech process. What happens then is a reduction in the dosage volume, since you only need 1 to 2 milliliters of a highly concentrated biotech drug for therapeutic effect. So, typically there are small dosage volumes, or in some cases dosage volumes can be several milliliters to permit a slightly longer-term infusion of a subcutaneous drug.
However, viscosity makes processing the fluid more challenging across the unit operations including the concentration step itself, but also through filtration, mixing, freeze/thaw, formulation, and dispensing. In addition, the smaller batch volumes that correspond with the increased concentration of the drug raises the cost of the Active Pharmaceutical Ingredient (API) per unit volume and this results in more significant impact with any product loss. Manufacturing challenges with high concentration drugs Next, we discussed some of the main challenges that exist in manufacturing workflows for high concentration mAbs. Tom said that he repeatedly hears from customers about challenges relating to product loss in hold up volume, aggregation of the molecules, limitations with analytical equipment and sampling procedures, and destabilization of filtered fluid due to the stripping out of formulation components.
Achieving high product concentrations
I then asked Gregor about the specific challenges to achieving high product concentrations. He explained that product viscosity is increasing with increasing product concentration. So, for a given crossflow, the pressures are also increasing with increasing product concentration. He went on to say that the permeate flux is decreasing with increasing product concentrations and therefore the processing times become longer, and the number of pump passes are much higher compared to low concentration processes. This combination of extended recirculation time and the increased concentration carries a significant risk of shear related damage that may impact the product quality. Finally, the high viscosity of the final retentate pools typically results in a poor recovery from TFF systems because of limited drainability.
I followed up by asking him which solutions can be app...
In this podcast we spoke with Derrick Alig, North American Western Regional Sales Manager for PSG Dover Biotech, Chris Couper, President and Founder of Liquidyne Process Technologies, and Phil Sanders Biotech Chief Innovation Officer at Agilitech about current supply chain challenges, possible solutions, what the future holds, and ways to navigate supply chain shortages to ensure manufacturers meet their timelines. Supply Chain Shortages I began the discussion by asking our panel members if they could discuss challenges that their customers are currently having with sourcing single use consumables and technologies. Derek began by discussing the lack of raw materials to make these products, whether it is polymer-based components where lead times have been extended due to lack of raw materials, or other areas such as chips. As a result, customers are having to purchase larger quantities of product in advance, which ultimately leads to even longer lead times.
Chris added that from a distribution perspective and an integrator perspective, many of their primary suppliers have had issues. They have also seen that many manufacturers have been able to ramp up their production with plants that were put in place in 2019-2020. However, it takes one to three years depending upon the complexity and the scope work to create additional manufacturing facilities and production lines. In addition, many manufacturers are using alternate materials. While they may have qualified one product in the past, now they are qualifying additional supply chains, so they have a primary supply chain and also secondary and tertiary chains.
Phil discussed bringing an agnostic approach to managing supply chain shortages to alleviate some of the issues of having a single source. He also pointed out that sometimes the focus is on single use supply chain issues, but there are companies using reusable equipment that are having some of the same supply chain issues, especially when it comes to these things like chips and control systems. Supply Chain Solutions Next, I asked the panel how their individual companies are approaching these challenges, specifically how they are working with customers to provide solutions for these challenges. Derek explained that at PSG Dover they are committed to providing quality products to customers in the biotech market. They focus on delivery times for customers by adding more shifts to keep up with demand and in late 2021, they added a second validated cleanroom to provide additional production capacities. They have also acquired companies to provide additional capacity.
Chris added that the situation could have been much worse if manufacturers had not stepped up and added capacity like PSG Dover and that they have seen improvements in lead times. He added that for Liquidyne they have a minimum of three supply chains for virtually every component that they offer. They let their customers know that they need to qualify the three components so they can be used interchangeably to meet timelines.
Phil added that maintaining flexibility is critical. For example, maybe the entire amount of inventory that is needed isn’t available now, but there is enough to get started while orders are placed for the rest of the material. Instead of trying to provide a customer with inventory for an entire year, provide three months' worth, then another three, and so on. Supply Chain in the Future I followed up by asking what they thought the future looks like for the supply chain over the next three to five years. Does this resolve itself or does it shift to another potential supply chain shortage? Derek said that he thinks that customers will continue to require multiple supply chain solutions and suppliers will also need to continue to add multiple sources for their raw materials and electrical components.
Chris said that he thinks companies that are successful will take the time to study what has occurred, how they reacted,
This article was originally published in the eBook “ Future proofing Bioprocessing from Upstream to Downstream”. You can download all the articles in the series, by downloading the eBook. Not everyone has the luxury of building from the ground up. How do you create a unified system between upstream and downstream with existing equipment and processes? And if you have the ability to build from the ground up, how can you ensure that your design is future proof? We spoke with Phil Sanders, Biotech Chief Innovation Officer from Agilitech, to develop a set of best practices for creating a holistic process from upstream to downstream.
Create a Growth Plan with Scalability Built in When companies are developing their process, it is easy to have a more myopic view of focusing on what is needed right now. Unfortunately, from a planning perspective this is very difficult because what is needed now often doesn’t work as companies need to scale up. When Agilitech works with customers, they ask customers to help them envision what their needs will be 3 years from now, 5 years from now, and at full commercialization. These answers are critical for decisions that companies will make right now. Because speed and cost are two driving factors, especially at the beginning of operation, companies often look for what is available now and what is the most cost-effective option. However, later they may learn that the process that they have created can’t scale up or can’t meet other process or quality related requirements. At that point, companies frequently wish they would have made different decisions earlier that took future needs into consideration.
One thing that Agilitech is helping customers with is bringing a holistic view. For instance, even if the project is related to upstream, it is important to think about what is the downstream going to look like. What will it look like in a process development environment, how about a manufacturing environment? Thinking about the scalability earlier in the process allows room to build scalability into the design for the future.
It is common in an industry that is always pushing for speed and efficiency to think about what must be produced now, but later customers often realize that they have wasted a tremendous amount of time creating a process and buying equipment that will ultimately need to be replaced for something that is more scalable or flexible; therefore, off-the-shelf is not always the best solution, even if it serves the purpose in the moment. Don’t Get Locked into a Proprietary Solution – Remain Brand Agnostic Agilitech Single-use Multipurpose Filtration Systems are Redefining FlexibilityThe benchtop option (up to 3 LPM) and larger system (up to 90 LPM) both adapt to virtually any external filtration system They can be used for multiple applications including sterile filtration, depth filtration, or virus filtration. Fit-forpurpose options permit reconfiguring the flow path to add more inlets, outlets, and more.
It can be tempting to lock into a single brand or a proprietary solution for your process needs from a convenience or discount standpoint. However, there are several reasons why you may want to remain brand agnostic.
Locking into a single solution may limit the process in the future. Often locking into a platform that works now results in limits on equipment size and volume that require redesigns that are costly and time consuming. A brand-agnostic approach allows companies to create a process that is flexible where all equipment works well together and communicates well across the entire process.
Proprietary software can be extremely limiting in scalability and working with other systems, particularly between upstream and downstream. Companies can find themselves in a situation where they must add another control system to expand their process for a more scalable solution.
Proprietary solutions can also impact support and whether updates and ...
In this podcast, we spoke with Dr. Brad Taylor from Nucleus Biologics and Randy Jacinto from Cytiva about the benefits of using a custom media for cell and gene therapy process development. Topics included current development challenges, increases in the number of cell and gene therapies in clinical trials, and employing custom cell culture media solutions to address these issues. We started the discussion by talking about the most pressing challenges facing cell and gene therapy development. Randy began by explaining that the most pressing challenges are the cost of manufacturing, lower than expected adoption rates, and complex logistics around supply chain. At Cytiva, he shared that they are addressing these challenges by automating many parts of the workflow and simplifying the logistics. In addition, the recent partnership with Nucleus Biologics will allow customers easy access to cell culture media solutions that can help accelerate the development of these cell therapies.
Brad added that he also hears from customers that there is difficulty accessing consistent, reliable products and materials in single source situations. Companies are working with suppliers who guard their materials with trade secrets and this hinders the ability for that therapy to progress to the clinic.
He went on to say that the scalability of cell therapies is also an issue, particularly as the industry moves into allogeneic therapies where manufacturing requires larger scale processes. He stressed that at Nucleus and in conjunction with Cytiva, they are committed to making sure that customers have a consistent supply of reagents and cell culture media to help them meet the rigorous quality standards. Next, I asked about what potential issues will arise with the large increase in cell and gene therapies in clinical trials, and the forecasted further increase over the next five years. Brad said that the regulatory approvals of cell therapies is really accelerating globally. Scaling processes for allogeneic therapies certainly lends itself to custom development and custom process development. So, it is important to not be locked into one size fits all type models. Nucleus wants to make sure that developers of these complex therapies can derisk their processes. Developers want to be able to accentuate desired attributes of their cell therapies and reduce those that are not desirable and cell culture media can have a profound impact in this area.
He went on to describe a collaboration with the University of Pennsylvania, where Nucleus demonstrated that individual components can help expedite therapies and improve outcomes. In those publications, authors were able to show an increase in in vivo efficacy, cytotoxicity, and transduction efficiency by changing the cell culture media components for CAR T cells.
Randy added that in addition to the scalability challenges, another primary challenge around cell therapies is the labor cost. Cytiva has estimated that labor costs contribute close to 48% of the total manufacturing costs of the drug therapy. To address these labor costs, Cytiva is working through automation as well as digitalization of the workflow and this will help overall improve the scalability and reduce costs. In addition, Cytiva is working with Nucleus Biologics because they truly believe that custom media is a key component in improving the overall efficacy of that drug therapy. Next, I asked about the focus of the Cytiva and Nucleus Biologics collaboration agreement and what they hoped to achieve together. Randy explained that it could not be a better partnership because the companies share a common vision of advancing novel therapeutics like cell therapies, which they believe will have a true transformative impact on the healthcare landscape.
He went on to say that the challenge has been with science workflows advancing much faster than the actual process of manufacturing itself.
In this podcast, I spoke with John Ketz and Denis Kole about viral vector production, including current manufacturing challenges, navigating the road to commercialization, and successful scale up strategies.
We began the interview by discussing the strides made in cell and gene therapy. Denis shared information about the several approved therapies and the more than 2,000 ongoing clinical trials. Denis added that while the immense potential of these personalized therapies is becoming more and more clear, the challenges and bottlenecks surrounding their development and manufacturing are also becoming a reality. This is especially true when it comes to producing and delivering sufficient amounts of these complex therapies in a reasonable timeline. He explained that patient demands are increasing and the increase in IND applications for cell and gene therapies is resulting in increased demand as well as competition for resources. Access to qualified labor has become a significant bottleneck and likely will continue to remain so, at least for the foreseeable near future.
He went on to say that the lack of standardized approaches for gene therapy modalities is another challenge that can increase the risk of failure. It can result in increased process complexity due to the need to screen large numbers of variables and can result in extended development times, which in turn affect the time to market for these needed therapeutics.
In addition, the availability of manufacturing capacity is also becoming quite limited with the field currently reporting a significant backlog that can extend as much as 16 to 18 months. John added that he also sees capacity issues and it is something that Andelyn Biosciences® is trying to address.
He also said that they are working on increasing speed and consistency. There are a lot of challenges that need to be addressed when moving from small flask or bench top scale into larger production scales. These may be challenges that you are not aware of or don't encounter at small scale. It is important to be mindful of this during scale up. Addressing Current Manufacturing Challenges To continue the discussion, I asked them to share the best way to address these challenges moving forward. Denis began by sharing that the demand for clinical and commercial manufacturing for advanced therapies is expected to continue to increase as more drug development companies entering the space and new therapies continuing their development journey. As a result, the manufacturing backlog currently observed will likely continue to remain present, if not expand. So, while large pharma and a few larger biotech companies may have the resources to internally support their clinical development and manufacturing needs, most of the smaller and medium sized drug development companies will continue to face challenges associated with quick access to qualified labor and access to extensive process expertise and available manufacturing capacity.
He went on to say that this is where groups like Pall’s Acellerator™ process development services and Andelyn Biosciences can play an important role with support through partnerships and collaborations. These types of collaborations really can provide the necessary resources and support for therapy developers to target shrinking the development timelines, reducing the risks associated with process development, and scaling to commercial scale. In addition, Pall and Danaher's integrated single use bioprocess offerings, provide scalable solutions that can reduce some of the risks associated with the development and manufacturing of therapeutics. These solutions really aim to alleviate some of the bottlenecks and risks associated with the lack of a standardized approach.
John added that at Andelyn Biosciences, they focus on creating a robust small scale model to ensure the consistency of the product when they move into larger scale.
In this podcast, I spoke with Hanna Lesch Ph.D., Chief Technology Officer at Exothera about viral vector manufacturing. We discussed current industry needs and challenges, scalability, end to end solutions, and key insights to a successful manufacturing and approval process.
I began the discussion by asking Hanna about the viral vector manufacturing that she is working on at Exothera. She explained that Exothera is a Belgium-based CDMO delivering customized process development and GMP manufacturing services for gene therapy and viral vector-based vaccines. In 18 months, they built their new facilities with a GMP qualified manufacturing area of 2100 square meters. They have flexible manufacturing solutions for adherent or suspension scale and can accommodate small to large scale manufacturing up to 2000 L.
Next, I asked if she could share her thoughts on current industry needs in terms of commercial scale production of viral vectors. She said that Exothera was founded to tackle two of the most critical challenges that manufacturers face in bringing advanced therapies to market – lack of production capacity and a shortage of bioprocessing expertise. Another area of focus is on cost of goods, as the cost of manufacturing a gene therapy product is significantly higher compared to conventional products. To reach as many patients as possible these treatments will need to be significantly less expensive.
To succeed in this, Hanna believes that the industry needs to overcome several challenges, including development of standardized processes, consistent product quality, and improving manufacturing yields. She added that today there are also major time constraint risks because of delays in raw materials or consumable supply.
We then discussed scalability and how Exothera manages their scale up needs. Hanna described how Exothera provides access to platforms, technical know-how and facilities to speed clients’ product development time. She said that Exothera has built their capability to serve process development from their parameter screening supported by design of experiments (DOEs), small scale bioreactors for process development, middle scale for process confirmation and large scale systems to meet high yield expectations. All available in both suspension and adherent cell culture. She stated that it is key to be able to provide the full path for the product lifecycle.
Then, I asked her how integrated end-to-end solutions can benefit viral vector manufacturing. She explained that end-to-end solutions can provide a fast track to clinic for their clients. This is supported by a strong technical, analytical and bioprocess know-how. These solutions also minimize the potential risks and surprises during development, providing lower cost and better predictability. She shared an example where they started a collaboration project aiming for quick AAV process scale-up into a 2000 Liter bioreactor in a very short time frame. Working with end-to-end providers, like Pall Corporation, is key to helping Exothera implement new technologies and infrastructure very quickly. She emphasized that time is money.
I then followed up and asked what advice she had for others who need scale up solutions. Hanna shared that making critical decisions about the manufacturing process carefully is important, as this can drastically increase the chances of succeeding the first time. Second, select an easily scalable technology. Last, know your viral construct to avoid any surprises later and ensure regulatory compliance and a solid testing strategy for both your product and your process to achieve a straightforward approval.
I closed the interview by asking Hanna if she had anything else to add for listeners. She said that if you don’t have a manufacturing platform ready, it is important to find the right partner who can support your development and your manufacturing success.
She also told me that she has an upcoming webinar,
In this podcast, we talked with Parth Trivedi, Business Development Manager, Pall Corporation, about the importance of implementing a Quality by Design strategy for AAV product manufacturing and specific key steps for successful assessment.
We began by talking about the importance of Quality by Design (QbD) in AAV product manufacture and how this pertains to the regulatory landscape. Parth explained that there have been several recent regulatory approvals of gene therapy products, but in 2020 there were also regulatory setbacks. These setbacks mostly involved lack of sufficient data in the chemistry, manufacturing, and controls documentation or CMC. This led Pall to create a framework for QbD assessment and implementation for AAV based products.
Parth pointed out that for over a decade the FDA has advocated for a QbD approach in pharmaceutical manufacturing and there is good documentation and regulatory guidance around this approach. QbD is heavily based on prior knowledge and detailed understanding of both the product and the process variables. Most of the industry’s experience in QbD has been in traditional drugs and now we need to learn and apply these principles to gene therapy products. Implementing Quality by Design I then asked Parth if he could talk a bit more about what companies should consider before implementing a QbD approach. He said that QbD relies on prior knowledge and detailed understanding of the product and the process, so prior to implementation, it is important to collect and generate information data, analyze it and interpret any process changes that have an impact on the product.
Thus, it is important to understand the quality target product profile (QTPP) and define it, focusing on specifications around the safety, purity, and efficacy of the drug product. A Framework for QbD Assessment for AAV Products I then asked Parth if he could discuss a recent white paper that Pall released, “Quality by Design (QbD) for Adeno-Associated Virus (AAV) - A Framework for a QbD Assessment for AAV Products Within the Chemistry Manufacturing and Controls (CMC) Documentation.” I asked him to walk listeners through the four steps that the Pall team identified in creating a risk- and science-based QbD assessment. Identification of CQAs based on QTPP and Risk Assessment Parth explained that in this step it is important to focus on the empirical view, starting with a deep understanding of product knowledge and process knowledge. The product knowledge is where you should focus on the QTPP and the critical quality attributes (CQAs) and the risk associated with it. He went on to say that how we identify CQAs depends on the drug substance or drug product’s physical, chemical, biological, and related characteristics, which will eventually impact the quality, purity, activity, efficacy, and safety of the drug. Another important consideration is impurity profiling, there are three categories an impurity can be profiled into - product related impurities, process related impurities and adventitious agents.
There are variations in the impurities, especially with upstream vs. the downstream. Specifically focusing on the AVV process on the upstream side, there are different processes that create different impurities, for instance - transfection process vs infection, adherent vs suspension, and mammalian cell vs. insect cell culture types. These parameters and the method of manufacturing will have its own impact on the process related impurities and product related impurities.
From there, it is important to know what the target product profile is and what the quality attributes are. Examples of common quality attributes are non-infectious AAVs, empty capsids, aggregated AAVs, and encapsulated host cell DNA. The next step is to ask which of these are critical attributes and this can be determined using a risk assessment guided by the ICH guidelines. Essentially looking at each attribute and assessing the risk assoc...
In this podcast, I talked with Dr. Jimmy Li, CEO of WuXi XDC, a WuXi Biologics subsidiary. We discussed the reasons for the formation of WuXi XDC, which was established via a joint venture between WuXi Biologics and WuXi STA, a WuXi AppTec subsidiary, and how one-stop drug development organizations greatly streamline a pathway to the clinic. He also shares new technologies available to make the development of Antibody Drug Conjugates (ADCs) more efficient and effective.
In this podcast, I talked with Dr. Jimmy Li, CEO of WuXi XDC, a WuXi Biologics subsidiary. We discussed the reasons for the formation of WuXi XDC, which was established via a joint venture between WuXi Biologics and WuXi STA, a WuXi AppTec subsidiary, and how this company provides a true single-source for the discovery, development, and GMP manufacture of antibody drug conjugates and other novel bioconjugates with their highly efficient one-stop drug development platform.
In this podcast, we talked with Dr. Alison Porter, Head of Expression System Sciences, Lonza, about the use of stable pool expression to reduce drug development timelines. Highlights included the implementation of stable pools in current workflows, expected titers, and cutting-edge applications of the technology.
Phil Sanders talks about the increase in demand for single-use equipment and consumables and how this has led to supply chain shortages.
Several of the most promising candidates in the pipeline use mesenchymal stromal cells and pluripotent stem cells, both of which require an adherent substrate for native biological function. Thus, utilizing an adherent platform for production of these cell types provides several advantages, including shorter process development and optimization time, no need to adapt cells to suspension, and the ability to implement various surface modifications that promote the relevant biology.
In this podcast, we spoke with Chris Rombach, Vice President of Sales and Marketing at Asahi Kasei Bioprocess America about buffer prep and delivery systems. We discussed current pain points and how next generation buffer prep solutions can greatly improve upon the status quo, including increasing the use of automation and remote operation, while reducing the overall footprint, labor and cost associated with more traditional approaches.
Claire Jarmey-Swan, Global Product Manager, Pall Corporation talks about the evolution freeze thaw technologies and how these new methods can streamline the process, minimize loss and maintain the highest product quality.
The priority of speed to market is often at odds with issues around development resources, facility space, and infrastructure for both development and manufacturing. Continuous bioprocessing provides solutions for many of these challenges in certain applications, but to deliver on this promise we need fit-for-purpose tools and technologies to enable process development and provide reliable transfer to commercial manufacturing.
Alan Dickson talks about the evolution of the CHO Cell line from isolation to workhorse of the biomanufacturing industry, to gene edited knockout variants. It is an interesting look at why CHO cells have been so successful and how this success continues to be improved upon for manufacture of emerging therapeutics.
In this podcast, Ratish Krishnan, Associate Director for Cell & Gene Therapy BioProcessing for the Americas at MilliporeSigma about the importance of 3D culture and the challenges associated with growing and maintaining culture in 3D. We also discussed using a 3D culture bioreactor system, which employs clinostat technology to culture spheroids and organoids in a way that maintains the structure and function of in vivo cells.
In this podcast, we spoke with Dr. Stephen Fey, Chief Research Officer and Co-founder, CelVivo about the importance of 3D culture and the challenges associated with growing and maintaining culture in 3D. We also discussed using a 3D culture bioreactor system, which employs clinostat technology to culture spheroids and organoids in a way that maintains the structure and function of in vivo cells.
Experts from Wuxi Biologics talk about one of the great technological advancements of the last decade, CRISPR/Cas9 technology. We discussed the technology’s potential and in particular its possibilities in the discovery and development of biopharmaceuticals. We also conducted a deep dive on its potential impact on bioprocessing and biomanufacturing.
In this podcast, we conducted a panel discussion with experts from Peak Proteins on common protein challenges and the use of mass spec to overcome expression and purification issues. We also discussed how mass spec can also be utilized in working with complex proteins and in-process modifications.
In this podcast, we spoke with Dr. Ann Rossi Bilodeau, Senior Bioprocess Applications Scientist and Dr. Catherine Siler, Field Applications Scientist both with Corning Life Sciences, who shared insightful tips for setting up a new lab. We discussed how to create a lab plan, maximize lab space, stay within budget and timelines. They also shared their experience in implementing lab safety and training as part of the new lab launch.
In this podcast, we talked with Chris Scanlon, Global Marketing Development Manager at Thermo Fisher Scientific about how to effectively evaluate which FBS product is right for each application. This includes weighing product quality levels and country of origin. Chris also shares strategies for maximizing purchasing options and new FBS products on the horizon.
In this podcast we talked with DQ Wang, PhD, and Vice President, Formulation, Fill and Finish of WuXi Biologics about their DP4 multi-product fill & finish facility featuring the Vanrx SA25 robotic, gloveless, isolator-based filling system. The system significantly reduces drug product fill risk and provides greater aseptic assurance.
In this podcast, we talked with Ken Chen, MBA, Senior Director, Regulatory Affairs, WuXi Biologics about staying current with regulatory changes. We discussed how WuXi Biologics recently began publishing a quarterly summary of regulatory updates on new or revised guidance documents from the various global regulatory agencies and how this is a valuable resource for anyone in the biological drug development arena.
In this podcast, we interviewed Markus Gershater, Chief Scientific Officer with Synthace about computer-aided biology and how it addresses several common biomanufacturing challenges. We also discussed ways to build a common culture between science and software.
In this podcast, we talked with Thierry Cournez Vice President, BioReliance® End-to-End Solutions, MilliporeSigma. We discussed effective ways for emerging biotechs to collect material quickly and cost-effectively for pre-clinical and clinical studies. We also discussed managing the need to move quickly with cost and quality.
In this podcast we talked with Christian Berg, Global Product Manager at Chemometec about the importance of standardizing cell counting because while often overlooked, it is essential for reproducibility in experiments, assays and manufacturing processes. Cell counting is a challenging technique, with many pitfalls, that can delay entire projects. We discussed how new technologies are solving these challenges and enabling standardization of cell counting across organizations.
This article is the fourth in a series that was published in the eBook “3D Model Systems: Spheroids, Organoids and Tissue Models”. You can download all the articles in the series, by downloading the eBook.
Introduction and Overview Debbie King Researchers have used 2D cell culture since the early 1900s, but we know that growing cells on planar surfaces have some drawbacks. Cells grown in vitro in 2D space don’t behave like cells found in vivo. They lack critical cell-cell and cell-matrix interactions that drive their form, function and response to external stimuli. This limits their prognostic capabilities. More recently, 3D cell culture techniques have become popular because the cell morphology, interactions and tissue-specific architecture more closely resembles that of in vivo tissues. Spheroids, organoids and more complex 3D tissue systems, such as ‘organ-on-a-chip’ are examples of 3D cultures used by researchers to model native tissues. Spheroids are simple, widely used 3D models that form based on the tendency of adherent cells to aggregate and can be generated from many different cell types. The multicellular tumor spheroid model is widely used in cancer research. Organoids are more complex 3D aggregates, more like miniaturized and simplified versions of an organ. They can be tissue or stem cell-derived with the ability to self-organize spatially and demonstrate organ-specific functionality. More complex yet, are technologies like organ-on-a-chip, which is a multi-channel 3D microfluidic cell culture system that mimics whole organ function with artificial vasculature. Cells are cultured in continuously perfused micrometer-sized chambers that recreate physiologically relevant levels of fluidic sheer force to allow for gas, nutrient and waste transport to the cell just as is observed in vivo vascularized tissues.
How are spheroids impacting cancer research and what do you see as future applications for the technology? Audrey Bergeron Spheroids can be an improved model for cancer in the lab compared to standard 2D cell culture. When cancer cells are cultured as spheroids, they are able to maintain the shape, polarity, genotype, and heterogeneity observed in vivo (1). This allows researchers to create models that are much more reflective of what’s going on in the body. For a simple example, if you think about drug penetration into a 2D monolayer of cells it’s completely different from drug penetration into a solid tumor. In a 2D monolayer each cell is exposed to the same concentration of drug whereas in a spheroid, like a solid tumor, there are gradients of drug exposure. More and more we’re seeing researchers move away from cancer cell lines and move more toward specialized cancer models such as patient derived models. The hope here is to find the appropriate therapies for each individual patient. (1) Antoni, D., Burckel, H., Josset, E., & Noel, G. (2015). Three-dimensional cell culture: a breakthrough in vivo. International journal of molecular sciences, 16(3), 5517–5527. doi:10.3390/ijms16035517.
What tools and technologies are needed to fully realize the potential of spheroid culture models? Debbie King One of the key parameters for success with spheroid culture is controlling the size of the spheroids. It can be very difficult to get consistent, reproducible results if the starting spheroid culture is not uniform in size and shape. Cell culture tools available on the market now, such as ultra-low attachment plates, facilitate the formation of uniformly sized spheroids for many research applications from low to high throughput modalities. Hilary Sherman There always needs to be a little bit of a balance between throughput and complexity in terms of creating models for research. That’s why there are so many options available for 3D research. Low attachment products such as Corning® spheroid microplate and Eplasia® plates are great for creating high throughput 3D models,
In this podcast, we talked with Dr. Gil Van Bokkelen, Chairman and CEO, Athersys about recent clinical breakthroughs in regenerative medicine and manufacturing challenges. We also discussed Multistem and how it has been demonstrated to help patients with ARDS (Acute Respiratory Distress Syndrome).
In this podcast, we conducted a panel discussion with experts from Selexis and KBI Biopharma on bi-specific antibodies. We examined bi-specific antibody development and manufacturing, including current challenges and key solutions. We also discussed the promise of these cutting-edge therapeutics and their future in medicine.
In this podcast, we talked with Dr. Glenn Harris, Director of Integrated Life Sciences Platforms at 908 Devices, about the benefits and challenges of implementing rapid media analysis in process development, including the bottleneck created by outsourcing samples to core labs. We also discussed an easy to implement, benchtop media analyzer that permits comprehensive media analysis in real-time, thus speeding process development efforts.
In this podcast, we talked with Dr. Tobias Hertzig, Regulatory Affairs Manager and Dr. Ulrich Tillmann, Global Product Manager, Supplements and Manufacturing Aids both representing Merck KGaA, Darmstadt, Germany. We discussed non-animal origin cell culture media supplements, including regulatory advantages, performance metrics and their use in biologics manufacturing.
In this podcast and accompanying article, we talked with Dr. Jennifer Chain, Scientific Director of Research and Development, Oklahoma Blood Institute about isolation of mesenchymal stromal cells from cadaveric bone marrow and the differences between live and cadaveric donors. We also discussed the expansion and maintenance of mesenchymal stromal cells in culture including media design and selection.
In this podcast, I talked with Max Blomberg, Executive Director of Operations and Andrew Govea, Senior Product Engineer, at Meissner about the challenges of handling bulk drug substance, specifically freeze and thaw and how the need for scalability, flexibility and a robust approach led to the development of CryoVault™. CryoVault™ offers a unique and intelligently designed end-to-end freeze and thaw process solution.
In this podcast and accompanying article, we talked with Paul Jantzen, Product Manager for IncuCyte at Sartorius about the benefits of real-time live-cell analysis and image processing workflows. We also discussed how live-cell analysis is enabling the use of neuronal cell models to study cell health, morphology, function and cell dynamics.
In this podcast and accompanying article, we interviewed Jonathan Royce, Director, Instruments Business Unit, Vironova about analytics in gene therapy manufacturing. Specifically Jonathan details new technologies to monitor critical quality attributes, reduce development time and increase the number of projects that can be run.
In this podcast and accompanying article, we talked with Dr. Paul Wotton, Chief Executive Officer, Obsidian Therapeutics about the evolution of cancer therapy and new advancements in the space including precision medicine. Our discussion included Obsidian's cytoDRiVE™ platform that provides a technology, in which the level and timing of protein activity are fully controlled in a dose-dependent manner by an FDA-approved small molecule.
In this podcast, we talk with Susana Alcantara, Senior R&D Scientist and Neuroscience Program Leader, BioAnalytics, Sartorius about the ways real-time live cell analysis is enabling neuroscience research. We also discussed how real-time cell analysis can be used in neurological disease model development and in studying disease pathology to enable drug discovery. Show Notes: I began the interview by asking Susana what she saw as the biggest challenges surrounding neuroscience research as it relates to cell monitoring and analysis. She explained that she saw the main challenges as being intrinsic to the type of research, specifically that the cells themselves are precious, difficult to obtain, costly and sensitive to handling. Researchers need to be able to sustain these cultures for long periods of time to analyze changes that occur, but common techniques use end point technologies and these aren't able to capture changes in culture over time and they can introduce artifacts.
To overcome these challenges, researchers need to avoid unnecessary handling of cells and minimize plate movement thereby providing a stable environment. They also need robust assays to maximize data obtained within each culture, including multiplexing or miniturizing assays. Lastly the development of live cell kinetic approaches is needed to model and monitor these complex neural systems.
Next, we discussed the platform that Sartorius has developed to enable cell research. Susana explained that the IncuCyte™ live cell analysis system is an imaging and analysis platform designed to minimize cell disturbance. The camera is on a mobile optical train allowing the culture to remain stationary. Images are then segmented by software that allows quantification in real-time and permits non-invasive measurements. The IncuCyte is flexible and enables the study of many aspects of neuroscience research including cell health and function. Sartorius has created several turnkey solutions including reagents, protocols and advanced software to support researchers.
We then talked about the advantages of real-time analysis as it relates to neuroscience research. Susana described that the brain is a complex system and its function depends on dynamic interplay between cells. In neuroscience research you must be able to evaluate temporal changes to understand how the brain functions in healthy and disease states. Researchers can evaluate these developments via temporal changes monitored using live cell analysis. Another important capability is repeated measurements to capture significant and subtle changes. Being able to do this in real-time permits real-time decisions to be made. For example, researchers can have a better understanding of when the culture is ready to be treated and this can enable method optimization. In addition, when an experiment fails, you can go back to the images and can quantify them retrospectively to see what went wrong and why.
Next I asked Susana about the assays that Sartorius has developed to assist in neuroscience research and workflows. She explained how the IncuCyte provides flexible analysis of multiple cell types using a combination of applications that have been developed. There has been a plethora of real-time protocols to look at cell health, morphological changes, and cell function.These assays provide unprecedented access to cellular changes over time.
I then brought up a white paper that I had read on how real-time live cell analysis can be used in neurological disease model development and in studying disease pathology to enable drug discovery. Susana said that the white paper had great real life examples of the applications developed for the IncuCyte. The applications covered in the white paper fell into three areas of study: neurodynamics, neuronal action and neuroimmunology research.
Another area that I wanted to touch on was how live cell analysis can compliment other end point technologies currently being us...
In this podcast and accompanying article, we interviewed Dr. Shareen Doak, Professor of Genotoxicology and Cancer at Swansea University Medical School and Dr. Wolfgang Moritz, Co-founder and Head of External Collaborations and IP, InSphero about the use of 3D cell-based human liver microtissue models to predict the adverse effects of chronic exposure to nanomaterial. We also discussed the use of liver microtissue models for drug discovery and development.
In this podcast, we interviewed Cory Card, Principal Scientist Life Sciences, GE Healthcare about raw material quality, its impact on cell culture and technologies to identify and mitigate raw material variation.
In this podcast, we interviewed Dr. J.J. Luo, Executive Director and Dr. Lily Yin, Head of Biologics Conjugation Development, at WuXi Biologics about the state of the ADC marketplace and the challenges in developing antibody drug conjugates. We then dove into reasons behind why they built a dedicated manufacturing facility for ADCs and other bioconjugates and how a single-source development platform can benefit bioconjugate drug development efforts.
In this podcast, we interviewed Dr. Manny Litchman, President and CEO, Mustang Bio and Dr. Knut Niss, Chief Technology Officer, Mustang Bio about the exciting study results for their gene therapy candidate to treat X-SCID, why this disease is a good fit for gene therapy and next steps.
In this podcast, we interviewed Dr. Andreas Castan, Principal Scientist at GE Healthcare Life Sciences about the best methods for optimizing perfusion processes. This included a discussion of tools for media optimization and innovative cell separation techniques.
In this podcast and accompanying article, we interviewed Dr. Kimberly Wicklund, Head of Product Management for the IncuCyte® at Sartorius about how live cell analysis is meeting the needs of advanced cell models and how the launch of the new IncuCyte SX1 is providing scientists more options when it comes to using live cell analysis in their workflows.
In this podcast and accompanying article, we interviewed Dr. Alex Chatel, Product Manager, Viral Applications, Univercells about the biggest challenges facing vaccine manufacturing today, why it is so difficult to manufacture and deliver vaccines to the developing world and how a novel technology with the support of the Gates Foundation is poised to address these challenges.
In this podcast and accompanying article, we interviewed Dr. Aline Zimmer, Head of R&D, Advanced Cell Culture Technologies at Merck about the importance of optimizing fed batch cell culture for successful biomanufacturing. Aline discussed how her team has developing new tools and methods for optimizing fed batch culture and the impact this has had on productivity and product quality.
Gibco Cell Culture Hero, Dr. Hillary Stires discusses her work researching better treatment options for triple positive breast cancer patients. She explains how the use of cell culture modeling helps drive her research. She also talks about her experience as a cell culture hero and her passion for the scicomm movement on social media platforms.
In this podcast, we interviewed Dr. Rick Morris, Senior Vice President, R&D, Biotech, Pall Life Sciences, about integrating bioprocessing steps to improve efficiency, reduce cost and address current challenges in the industry. Specifically we looked at how upstream and downstream can be more integrated and how to increase integration in existing facilities.
In this podcast and accompanying article, we interviewed Mr. Dave Eansor President of the Protein Sciences Segment at Bio-Techne and Dr. Sean Kevlahan, Senior Director of Cell and Gene Therapy at Bio-Techne about new technologies that can be implemented to expedite cell therapy and gene therapy workflows and facilitate the path from bench to clinic.
In this podcast and accompanying article, we interviewed Dr. Andreas Castan, Principal Scientist at GE Healthcare Life Sciences about the most efficient ways to optimize fed-batch cell culture production for CHO-based antibodies. This included a discussion of media vs. feed strategies, incorporating critical quality attributes, evaluating the impact of optimizing on downstream processing and more.
In this podcast and accompanying article, we interviewed Dr. Mats Lundgren, PhD Customer Applications Director, Life Sciences, GE Healthcare, Sweden about developing platform processes for viral vector manufacturing and Mats describes a recently developed platform process for adenovirus production.
Panel discussion that I moderated at this year’s Cell and Gene Therapy Bioprocessing and Commercialization Conference. The discussion covers the latest in gene therapy manufacturing strategies, analytical analysis, cost of goods and key regulatory considerations.
Panel discussion on key considerations for moving cell therapies from lab to commercial manufacturing, including the benefits of manufacturing in a closed system. We also discussed what were some of the key hurdles and possible solutions associated with transitioning to clinical and commercial cell therapy manufacturing.
Dr. Ross Macdonald, CEO Cynata Therapeutics, talks about the use of mesenchymal stem cells for Cell Therapy applications and key criteria for successful mesenchymal stem cell manufacturing.
Ricardo Baptista, Lead Process Development Scientist, Cell and Gene Therapy Catapult, UK talks about his impressions on current bioprocessing technologies for stem Cell Therapy manufacturing and possible future innovations.
Dr. Robert Preti talks about the past, present, and future of global Cell Therapy manufacturing. We also discussed major industry milestones, manufacturing challenges, and opportunities for further improvements.
Dr. Paul Wotton, CEO, talks about Sigilon Therapeutics’ discovery platform. The platform combines cell engineering and biocompatible Afibromer™ technology to enable cell therapeutics that do not trigger fibrosis.
Alyssa Master, Ph.D., Senior Manager of Science and Applications, Nucleus Biologics talks about some of the challenges of working with FBS, why not all FBS is created equal and suggestions for FBS customers who are trying to navigate these issues.
Dr. Adam Elhofy, Ph.D., Chief Scientific Officer, Bio-Ess Laboratories, talks about the relationship between antibody titer and product quality attributes such as glycosylation. Dr. Elhofy shares his thoughts on both challenges and opportunities in optimizing for both high titer and glycosylation profiles.
Ken Clapp, a senior member of GE Healthcare Life Sciences' upstream product management team explores in more detail the implementation of single-use systems for microbial fermentation including which processes make good candidates for single-use and considerations for transitioning from stainless steel.
Ken Clapp, a senior member of GE Healthcare Life Sciences' upstream product management team discusses the use of single-use bioreactors for fermentation, how single-use technology has evolved to meet the more rigorous demands of fermentation, and the benefits of single-use for this application.
Jim McGorry, CEO and Saverio LaFrancesca, President and Chief Medical Officer talk about how Biostage is using Cell Therapy to improve the standard of care in adult and pediatric esophageal disease.
Sarah Simons, Automation Field Project Manager, Beckman Coulter Life Science talks about how to improve lab productivity and reproducibility by "spring cleaning" your methods and taking a fresh look at existing workflows and protocols.
Philip Mathuis, Co-founder and CEO, Ovizio, talks about cell culture monitoring, the latest technology for monitoring cells in culture without the need for sampling, and where monitoring could move in the future.
In this podcast, we were fortunate to have a group of experts for a panel discussion on vaccine manufacturing and viral vector production.
In this podcast, we interviewed Dr. Adam Elhofy, Ph.D., CSO, Essential Pharmaceuticals, about cell culture media optimization. We discussed the evolution of cell culture media optimization, current goals, and the latest strategies and tools being used.
In this podcast, we interviewed Dr. Jan Bruder about his work at the Max Planck Institute for Molecular Biology in Münster Germany and his group’s use of automated high throughput drug screening program for ALS and Parkinson’s Disease.