Wednesday, September 25, 2024 - Day Two of Main Conference - EST/EDT (Eastern Daylight, GMT-4)
Wednesday, September 25, 2024 - Day Two of Main Conference - EST/EDT (Eastern Daylight, GMT-4)
- Kartik Subramanian - Vice President, Bioprocess Development, AbbVie Bioresearch Center, USA
- Jon Coffman - Executive Director of Bioprocess Technology and Engineering, Astra Zeneca
Mammalian cell bioprocesses have been monitored traditionally by off-line staining of cell samples. Newer techniques can offer rapid and continuous monitoring without manual sampling. Novel optical and dielectric protocols will be explained and discussed as alternatives for monitoring cells in bioprocesses. These methods can be used to provide growth profiles as well as the metabolic status of cell populations. They offer distinct advantages as in-line or at-line monitoring tools.
- Michael Butler - Principal Investigator, NIBRT
- Yanling Wang - Sr. Director of Synthetic Biology, Protein Expression, Henlius
- Kurtis Denny - Senior Engineer I, Cell Culture Development, Biogen
We present a digital twin model-based process control (MPC) strategy for the successful glucose feeding in a bioreactor using only daily offline measurements. Our MPC strategy is composed of two kinds of formulars for predicting 1) glucose feeding amounts at daily sample time-points and 2) glucose feeding amounts at unsampled time-points.
- Min Cheol Kim - Process Engineer IV, Sanofi
- Irina Ramos, Ph.D - Director of Bioprocess Technology and Engineering, AstraZeneca
- Jay (Zizhao) Liu, Ph.D. - Senior Process Scientist, Downstream Sciences, Process Sciences Department, Regeneron
- Jeff Johnson - President, Biotech Design, LLC
- Specific and strategic considerations for process and analytical development of advanced therapies
- Optimising and scaling-up of manufacturing operations post approval
- Preparing for regulatory filing
- E. Morrey Atkinson, PhD - EVP, Chief Technical Operations Officer, Head of Biopharmaceutical Sciences and Manufacturing Operations, Vertex Pharmaceuticals
Control and management of materials is a key pillar of GMP manufacturing. An initiative is in progress which aims to harmonize the approaches of material management between clinical and commercial Drug Substance production sites to increase efficiency and supply chain sustainability within the organization. We will present the background and drivers, strategies, and current status of this initiative.
- Dale R.Mowrey - Associate Director of Material Science, Teva Pharmaceuticals
- Kaitlin Kestenberg - Senior Vice President, Compliance & Project Operations, ADMA Biologics
- Saeed Izadi, Ph.D. - Senior Principal Scientist & Group Leader, Genentech, Inc.
- The development of first in class novel complexed miRNA-based cellular reprogramming therapeutics
- Exploring the use of miRNA for the treatment of Alzheimer’s Disease, Diabetes and Heart Disease
- Joseph Cahlifoux - Founder & CEO, Athergen
- Overcoming hurdles of viral vectors for Gene Therapy by harnessing the power of non-viral DNA-based platforms for Advanced Therapeutics
- Advancing Beyond Lipid Nanoparticles: Innovative Strategies in Delivery Vehicles Technology
- Exploring the use of DNA-based therapeutics for the treatment of diabetes, anemia and cancer in animal and human health.
- Case Reports
- Martin Williams - Founder and CEO, SYTE.bio
- Amish Patel - SVP, Technical Activity Committee at NIIMBL, Calidi Biotherapeutics
This presentation will focus on the technical and manufacturing capabilities for cell therapy commercialization with discussion of CMC requirements, manufacturing launch readiness, and supply considerations. Specific considerations for a cell therapy and partnership with contract manufacturing organizations will also be discussed including lessons learned.
- Kenneth Green, PhD - Snr Dir MSAT, Vertex
- Sylvian Roy - CTO, ImmPACT Bio
Increasing demand for recombinant adeno-associated virus (rAAV) based gene therapies necessitates increased manufacturing production. Transient transfection of mammalian cells remains the most commonly used method to produce clinical-grade rAAVs due to its ease of implementation. However, transient transfection processes are often characterized by sub-optimal yields and low fractions of filled-to-total capsids, both of which contribute to the high cost of goods of many rAAV-based gene therapies. Analysis of our previously developed mechanistic model for rAAV2/5 production suggested that the inadequate capsid filling is due to a temporal misalignment between viral DNA replication and capsid synthesis within the cells and the repression of later phase capsid formation by Rep proteins. We experimentally validated this prediction and showed that performing multiple, time-separated doses of plasmid increases the production of rAAV. In this study, we utilize the insights generated by our mechanistic model to develop an intensified process for rAAV production that combines continuous perfusion, high cell density transfection, and re-transfection which resulted in increased titer and plasmid efficiency. Our results establish a new paradigm for continuously manufacturing rAAV via transient transfection that improves productivity and reduces manufacturing costs.
- Tam Nguyen - Scientist, BioNTech US / Massachusetts Institute of Technology
AAV has emerged as a significant therapeutic modality in gene therapy. Challenges such as poor yield and variable product quality persist in the viral vector manufacturing space and we have addressed these problems using our cell engineering technology. Our cell engineering platform for improved adeno-associated virus (AAV) manufacturing addresses the critical challenges in gene therapy manufacturing, and presents an innovative modality for improving cells for production of viral vector therapeutics. Our platform, yielding cells with improved AAV production and CQAs, can significantly bolster the efficiency and cost-effectiveness of gene therapy manufacturing, and can accelerate current development timelines. We used a directed-evolution approach based on repeated cell fusions to shuffle the cell genome, and amplify chromosomes of HEK-293 host cells. Engineered clones enriched for mitochondria phenotypes were isolated, then used as transient-transfection hosts, and for creating stable packaging and producer cell lines. For generation of stable packaging and producer cell lines, we developed a novel inducible system that maximizes the capabilities of the inherent viral production machinery. Engineered HEK-293 clones grown in suspension culture exhibited up to 15-fold productivity improvement via triple transient transfection for AAV1, AAV2, AAV5, and AAV9 serotypes with capsid titers as high as 1017 viral particles/L (vp/L)—at least 10-fold higher than current industrial manufacturing processes. Selection for certain mitochondria phenotypes resulted in a 2-fold improvement in full-to-empty ratio—up to 55% full in crude supernatants. Finally, our engineered stable packaging and producer cell lines achieved capsid titers of up to 1016 vp/L. We demonstrated a multi-modal cell-engineering platform that has significantly improved yield and manufacturability for transient transfection and for stable packaging and producer cell line methods. We further propose a model regarding the role of mitochondria for enhancing capsid percent-full. Taken together, our disruptive platform technologies provide solutions for meeting current—and future—gene therapy manufacturing challenges.
- Larry Forman - CEO, CHO PLUS
- Sanjeev Gupta - Sr. Vice President and Head Biosimilars, Ipca Laboratories
Chinese hamster ovary (CHO) cells are the most widely used mammalian host for industrial-scale production of mAbs and other protein biologics. Selection of high-producing cell lines is a major endeavor in the process of manufacturing a novel biologic and requires an extensive and lengthy screening campaign of several hundreds of clonally-derived cell lines. We have previously reported the development of an efficient cumate-inducible expression system. Here, we present a new GMP-banked parental cell line, amenable to both constitutive or cumate-inducible expression. We first present our process for selecting CHO pools in suspension culture and then cell lines using a semi-automated approach, where imaging analysis provides >99% probability that selected cell lines are single-cell derived. Recent plasmid engineering efforts allowed to increase cell line productivity by 75% where~70% of selected clones show stable expression after at least 60 generations in culture. We also present recent development of a selection approach allowing to screen for more productive CHO minipools prior to single cell cloning. Optimizing several parameters such as cDNA sequence, signal peptide sequence, and suspension minipool selection process, we were able to increase titer for IgG1s from 2.5-3.0 g/L to 5.5 g/L using commercial medium and feed. Finally, we present data supporting the use of stable cumate-inducible CHO pools for clinical development of trimeric SARS-CoV-2 spike subunit vaccine antigens.
- Simon Joubert - Team Leader, Cell Line Development, National Research Council Canada
Continuous manufacturing has become more prevalent across the biopharmaceutical industry in recent years. The ambr250ht perfusion system stands as a promising option for bench-scale culture work, but first must be proven as a replacement for the more common 3L scale. Through statistical analysis, the differences and similarities between these scales can be investigated to qualify their equivalence
- Zayla Schaeffer - Scientist, AstraZeneca
Generic Raman spectroscopy models, built using data from multiple processes, offer a method for streamlining Raman model development and integration in upstream bioprocessing. Effective implementation of generic Raman models requires consideration of several factors, such as the presence of any biases in the calibration dataset. The large volume of data used to develop generic Raman models also makes them ideal for creating hierarchical Raman models, which use the outputs of one or more base models as the inputs for a new model—e.g., cell culture pH.
- Alex Williams - Senior Associate Scientist, Biologics Development, Global Product Development and Supply, Bristol-Myers Squibb
- Chris Furcht, Ph.D - Associate Director, Biologics Development, BMS
- Sushil Bahatia - Senior Process Scientist, Regeneron
- Addressing unique needs for vaccine modalities
- Optimization of PAT and tech transfer
- Scalability considerations
- Managing internal and external manufacturing operations
- Chase Orsello - Head of Bioprocess, Sanofi
- The importance and advantages of microbial systems in biopharmaceuticals
- Platform for non-mAb biopharmaceutical development
- High Throughput process development
- CASPON technology a solution for the development of therapeutic peptides
- Future prospects, such as sustainability and competitiveness
- Cécile Brocard - Director Downstream Development, DevOps Austria, Boehringer Ingelheim RCV GmbH & Co KG
- Li Jing, PhD - Senior Manager, USP
- Vamsikrishna Kandhi, Ph.D - Principal Scientist, Pfizer
Aurion Biotech is taking their off-the-shelf, allogeneic cell therapy (AURN001) from the lab to clinical trials with the goal of becoming the first mass-scale cell therapy to help restore vision to 17M+ patients around the world with corneal endothelial disease. Building a mass scale cell therapy means:
- Fulfilling a significant unmet patient need caused by the global shortage of donor corneas for transplant, in ways that are accessible and equitable
- Navigating the highs and lows of manufacturing and scaling an allogeneic cell therapy for clinical trials, successfully managing a CDMO partner and establishing a development process that can be translated into a large-scale commercial product.
- Creating a breakthrough product that will transform the physician experience – one that is less complex and less invasive than corneal transplant (the current standard of care) and minimally invasive for patients.
- Eris Jordan - Global Vice President, Clinical and Medical Affairs, Aurion Biotech
- Dethardt Müeller - Chief Technology Officer - CMC, Abalos Therapeutics GmbH
Automation plays a key role in improving the quality and lowering the cost of cell therapy products. As new or improved processing and testing technologies enter the market, it’s important for firms that build these products to design and provide both digital and physical integration touchpoints for their systems and consumables. This overview will discuss some of these important design considerations that will allow for more effective implementation of automation and make it easier to adopt new technologies.
- Dmitry Fradkin - Director of Automation Systems Development, Kite Pharma
Allogeneic cell therapies present a unique challenge for drug product process development by combining aspects of autologous cell therapies and conventional biologic products. As production scale increases to that of a commercial, off-the-shelf therapy, new challenges emerge for expanding fill finish and cryopreservation capacity. This presentation will discuss the developments and considerations that are necessary for pursuing large scale, allogeneic cell therapy manufacturing.
- Rae Stephenson - Senior Research Associate - Cell Therapy Drug Product, Sanofi
Ultragenyx is developing an investigational gene therapy, UX701, an adeno-associated viral vector-based gene therapy product, for the treatment of Wilson disease. UX701 is an investigational AAV9 gene therapy designed to deliver a modified form of the ATP7B gene. Ultragenyx has initiated Cyprus2+, a seamless Phase 1/2/3 study of a single intravenous infusion of UX701 in Wilson disease (NCT04884815). UX701 leverages Ultragenyx’s proprietary producer cell line platform, Pinnacle PCL™. This presentation reviews our first late-stage development activities for our upstream Pinnacle PCL™ platform process including parameter risk assessment, scale-down model qualification, and process characterization, to establish process controls for the upstream unit operations in our 2000L manufacturing process. The process characterization studies help us understand our parameter space and mitigate operational and quality risks which are critical for successful implementation of a robust commercial manufacturing process to provide consistent product quality throughout the product’s lifecycle.
- Jun Li - Associate Director, Upstream Process Development, Gene Therapy, Ultragenyx Pharmaceutical
Abstract TBC
- Paetra Brailsford - Engineer III, Technical Development, Biogen
The Cell Line Development (CLD) group within the Genomic Medicine Unit CMC department at Sanofi is dedicated to the establishment of best-in-class Producer Cell Lines (PCLs) for manufacturing of life-changing gene therapy products. The development of a robust PCL requires optimization of a multitude of process and operating factors; however, additional functionality can also be unlocked through the implementation of an automation-enabled and data-driven workflow. We have implemented several enhancements in our PCL development process, including liquid handling automation and state-of-the-art automated cell imaging and seeding systems. This newly developed automation-enabled next-generation process will lead future high-throughput capabilities for PCL development.
- Karin Plante - Senior Research Associate, Automation Lead, AAV Producer Cell Line Development, Sanofi
Cell lines derived from the caterpillar, Spodoptera frugiperda (Sf), are the most commonly used hosts in the baculovirus-insect cell system (BICS), but they can harbor Sf-rhabdovirus (Sf-RV) contaminants. In this presentation, I will review our efforts to isolate the first Sf-RV negative (Sf-RVN™) Sf cell line, as well as the characteristics of this cell line indicating it is an improved, seamless alternative for Sf-RV-contaminated lines.
- Don Jarvis, Ph.D. - President, GlycoBac, LLC
The volumes of data generated by upstream bioprocesses during development, technology transfer and GMP production are only as good as the tools to make the data available for consumption and advanced data analytics. This talk will provide current highlights from our 12-year journey digitizing bench and pilot scale bioreactor processes to enable paperless data aggregation and generation of persona dashboards for daily analysis by data consumers and executives alike.
- Michelle Lafond - Vice President of Preclinical Manufacturing and Process Development, Regeneron
- Specific improvements in cell culture media formulations
- The impact of enhanced media on cell growth and productivity
- Challenges and potential solutions in adopting better cell culture media
- Balancing pH and osmolality for an optimal culture environment
- Pallevi Srivastava - Head of Process Development, Wildtype
- Juan Manuel Marin-Celis - Bio-Separations Scientist, Merck
The biopharmaceutical industry is increasingly confronted with the dual challenges of complex product demands and a volatile market landscape, necessitating unprecedented levels of supply chain agility and resilience. This presentation addresses the critical role of digital innovation in transforming biopharma supply chains, enabling them to adapt swiftly to market fluctuations and unexpected disruptions. We explore the integration of advanced technologies such as artificial intelligence (AI), and machine learning (ML) to enhance visibility, optimize operations, and improve decision-making processes. Through case studies and industry insights, we demonstrate how digital tools can facilitate precise inventory management, robust cold chain logistics, and regulatory compliance, thereby reducing waste and ensuring timely delivery of vital products.
- Imara Charles - VP, Process and Digital Excellence, Global Supply Chain, Bristol Meyers Squibb
- Elisabeth Krug - Executive Director, BRD Analytical Development, Eli Lilly & Company
- Jeffrey Baker - Senior Fellow, NIIMBL; Strategic Advisor, CBI-MIT
- How can early-stage/research professionals best prepare for GMP
- Critical aspects to keep in mind transitioning from early-stage development into more commercial manufacturing.
- Examples from experiences and lessons learnt
- Cross-team collaboration and pre-emptively preventing down the road bottlenecks
- Shashi Murthy, PhD - CTO and Co-Founder, Nanite Inc.
- Jared Auclair - Associate Dean of Professional Program and Graduate Affairs, College of Science at Northeastern University
- How can early-stage/research professionals best prepare for GMP
- Critical aspects to keep in mind transitioning from early-stage development into more commercial manufacturing.
- Examples from experiences and lessons learnt
- Cross-team collaboration and pre-emptively preventing down the road bottlenecks
- Shashi Murthy, PhD - CTO and Co-Founder, Nanite Inc.
- Jared Auclair - Associate Dean of Professional Program and Graduate Affairs, College of Science at Northeastern University
- How can early-stage/research professionals best prepare for GMP
- Critical aspects to keep in mind transitioning from early-stage development into more commercial manufacturing.
- Examples from experiences and lessons learnt
- Cross-team collaboration and pre-emptively preventing down the road bottlenecks
- Shashi Murthy, PhD - CTO and Co-Founder, Nanite Inc.
- Jared Auclair - Associate Dean of Professional Program and Graduate Affairs, College of Science at Northeastern University