Thursday, September 26, 2024 - Day Three of Main Conference - EST/EDT (Eastern Daylight, GMT-4)
Thursday, September 26, 2024 - Day Three of Main Conference - EST/EDT (Eastern Daylight, GMT-4)
Production of biologics require adequate cellular capacity to maintain desired productivity and quality. Topics covered include how tuned energy supply improve secreted productivity in HEK293. How tuning of secretory helper proteins in CHO increase level of active sulfatase product 150-fold. We will also cover cell and protein engineering strategies for improved AAV production.
- Johan Rockberg - Professor, KTH Royal Institute of Technology
- Emphasize the advantages of not dealing with cell growth, maintenance, and contamination
- Explore innovations and strategies aimed at making cell-free bioprocessing economically feasible
- Reduce COGs for large-scale cell-free systems
- James Zawada - Associate Director Process Science, Sutro Biopharma
How it will work is we have 3 Round Tables each covering a different challenge of Upstream & Cell Culture in Bioprocessing. Each will be led by an expert. The expert will kick off and guide the discussion which will last for 30 minutes. At the end of the 30 minutes the leader will report their main conclusions to the room for a maximum of 10 minutes.
Roundtable Discussions
Cell Culture Optimization
- Cell Line Development: Selecting and developing an optimal cell line is crucial for achieving high product yields and quality. Identifying a cell line with desirable characteristics, such as growth rate, productivity, and stability, can be a time-consuming and complex process.
- Cultivation Conditions: Maintaining optimal conditions for cell growth and productivity is challenging. Factors like temperature, pH, nutrient availability, and gas exchange need to be carefully controlled to ensure optimal performance. Achieving consistent and reproducible results across large-scale bioreactors adds another layer of complexity
Bioreactor Scale-Up:
- Transition from Lab Scale to Production Scale: Scaling up bioprocesses from small laboratory bioreactors to large-scale production facilities can lead to challenges in maintaining consistent conditions. Factors like mixing, mass transfer, and heat dissipation become more complex as the scale increases. Achieving uniform distribution of nutrients and gases becomes crucial for maintaining cell health and product quality. Take into account Perfusion versus Fed-Batch.
- Bioreactor Design: The design of bioreactors for large-scale production must consider factors such as hydrodynamics, shear stress, and heat transfer to ensure optimal cell growth and product formation. Choosing the right type of bioreactor and ensuring scalability without compromising performance is a significant challenge
Process Monitoring and Control:
- Real-time Monitoring: Continuous monitoring of various parameters, such as cell viability, metabolite concentrations, and product titer, is essential for process control and optimization. Implementing reliable real-time monitoring techniques can be challenging, particularly for complex bioprocesses.
- Process Control: Maintaining tight control over the bioprocess is crucial to achieve consistent product quality. Controlling variables such as pH, dissolved oxygen, and nutrient concentrations requires advanced control strategies. Deviations from optimal conditions can negatively impact cell growth, viability, and product quality
- Swetha Kumar - Scientist, Sanofi
- Lara E. Krebs - Advisor - Bioprocess Research and Development, Eli Lilly and Company
- Tingting Cui, Ph.D. - Associate Principal Scientist, AstraZeneca
- Qian Ruan, Ph.D - Senior Vice president of TechOps and Supply Chain, Arcturus Therapeutics
- How are regulatory agencies approaching the rapid adoption of advanced technologies?
- What will the regulatory framework for the implementation of AI look like?
- How can regulatory agencies and industry work together to make safe and smart manufacturing a reality?
- Qian Ruan, Ph.D - Senior Vice president of TechOps and Supply Chain, Arcturus Therapeutics
- Johnson Varghese - Head of Analytical Sciences & Development, Beam Therapeutics
Dark Horse Consulting Representative
- Unpacking the current barriers to RNA gene therapy use
- Advancements in the processing of RNA to improve outcomes (remove unwanted cells, viral concentration, purification)
- Scalable processes
- Approaches to reaching high yield downstream purification
- Removing aggregates and contaminates from your titer
- Removal of partially-full capsids from your full-capsid yield
- Seema Bhatlekar - Scientist, Johnson & Johnson Innovative Medicine
- Shashi Murthy, PhD - CTO and Co-Founder, Nanite Inc.
- Tailored design and engineering of polymeric nanoparticles for optimal cell interaction, targeting, and therapeutic delivery.
- Diverse delivery strategies and tissue targeting approaches for specific disease applications
- Effective encapsulation techniques to preserve cell viability, functionality, and differentiation potential during delivery
- Case study: how are these being explored/used
Cell-based manufacturing of gene therapy molecules presents multiple challenges in maintaining high product yield and quality. Traditionally, isolating the desired DNA molecules is challenging. Additionally, cell-based approaches require long manufacturing timelines. To address these speed and quality challenges, we developed an enzymatic method capable of producing DNA drug substance at g/L scale and with >99% purity using chromatographic methods. This cell-free process has enabled highly accelerated production timelines compared to cell-based methods and the enzymatic platform facilitates diverse production application with constructs up to at least 7000bp in size.
- Anthony Dawson - Senior Scientist, Generation Bio
- Duncan McVey, Ph.D. - Associate Director, Bristol-Myers Squibb
Transposase-mediated semi-targeted transgene integration systems deliver highly productive and genetically stable clones; however, it is sometimes challenging to characterize target gene integration sites for production cell lines with relatively higher gene copy numbers. This presentation will discuss the use of NGS and in silico predictive tools to support the generation of cell line stability data package to meet regulatory expectations.
- Hyo-Young Jeong,PhD - Senior Scientist, Process Cell Sciences, Merck & Co Inc.
This presentation describes a process characterization (PC) study that evaluated the effect of three vial thaw parameters using a fractional factorial design. This study aimed to identify an optimal thawing process that maximizes cell viability and density. Results from this study have contributed to the standardization and refinement of the vial thaw process, particularly through a DOE approach focused on two molecules, thereby establishing best practices for the vial thaw procedure platform
- Yuan Yuan - Sr Scientist, Cell Culture Development, Teva Pharmaceuticals
Glycosylation profiles are essential to the quality and potency of therapeutic biologics produced from CHO cells. Culture medium formulations significantly impact the N-glycosylation of biologics, which is critical for protein structure and bioactivities. In this case study, improvements in the culture medium by supplementing specific metal ion / small molecule components altered the N-glycan profile and enhanced its biological activity in-vivo.
- Yingxue Zhang - Scientist, Upstream Process Development, Jecho Labs
- Jason Souvaliotis - Associate Scientist, Biopharmaceutical Drug Substance Process Development, GSK
- Vivek Kumar Muthusamy - Process Development Senior Scientist, Amgen
In the slowly evolving landscape of bioprocess development and manufacturing, digital bioprocess-twins have emerged as potential accelerators. While advanced algorithms are at the heart of this endeavor, they are just one piece of the puzzle. The talk delves into key discussion points that are integral to this paradigm shift. The foundation of accelerated process development and automated process control starts with a clever experimental design, in-time data accessibility combined with powerful modeling algorithms. The talk will highlight the advantages of using hybrid modeling, while emphasizing the other critical aspects of his journey. Several industrial relevant upstream showcases for microbial and mammalian cell lines will be highlighted. Thereby, concepts to save experimental effort by up to 70% will be elaborated, and the modeling structure created in the late-stage development will be reused for real-time monitoring and control in the later stages. Additionally, a downstream optimization showcase for UF/DF/SPTFF will be highlighted.
- Mark Duerkop - Chief Executive Officer, Novasign
Continuous improvement methodology has been employed for many years to improve manufacturing where effectiveness depends on team experience. Advanced modeling technology for biomanufacturing promises to make continuous improvement methodology more widespread and allow teams to achieve expert results with far less experience. This presentation will illustrate model based continuous improvement across a drug substance biomanufacturing process using an industrial case study.
- Joseph Pekny - Professor, Chemical Engineering, Purdue University
- Yiwei Zhao - Director, Analytical Development, Mural Oncology
- Nadine Ritter, Ph.D. - President and Analytical Advisor, Global Biotech Experts, LLC
This presentation delves into the evolving landscape of supply chain management for CGTs, offering insights into the latest developments that are reshaping the industry. The session begins with an overview of traditional supply chain practices, highlighting their limitations and the pressing need for adaptation in an ever-changing global market. From there, it transitions into an exploration of cutting-edge innovations such as artificial intelligence (AI), machine learning, blockchain technology, and Internet of Things (IoT). These technologies are revolutionizing supply chain processes, enhancing efficiency, visibility, and responsiveness across the entire network. We will also consider predictive analytics to digital twins and autonomous systems, which can empower organizations to anticipate disruptions, optimize inventory management, and streamline operations for maximum effectiveness. In addition, we will consider sustainability initiatives, circular economy practices, agile supply chains, and the integration of advanced robotics and automation. By offering a comprehensive overview of these innovations, tools, and trends, attendees will be equipped with the knowledge and insights necessary to navigate the complexities of modern supply chain management.
- Jared Auclair - Associate Dean of Professional Program and Graduate Affairs, College of Science at Northeastern University
Many pharma and biotech companies onboarded thousands of materials and increased inventory during the pandemic. With the endemic in full swing, organizations have a surplus of material that is about to or has already expired. This presentation seeks to explain how the presenter worked to extend the shelf life of various materials for continuity improvement and financial savings.
- Michelle Parziale - Senior Engineer - MS&T, Moderna
- Scalable methods to optimize EV Isolation & Purification
- Efficient techniques for manipulating EV properties (size, surface ligands, cargo loading etc.) for enhanced targeting and in vivo delivery
- Challenges and potential strategies for adhering to strict GMP regulations for clinical-grade EV production.
- Christopher Locher - CEO & Co-Founder, Versatope, USA
We developed CRISPR-Cas9 mediated engineered universal stem cells, via elimination of MHC-I/II and targeted insertions of NK and macrophage-resistant factors. We explored the use of a kill switch to remove cells if required. Our precise gene-editing approach generated well characterized GMP compatible clonal hypoimmunogenic lines, minimizing off-target effects. These cells differentiated into human ventricular progenitor cells maturing into cardiomyocytes. This work paves the way for off-the-shelf, allogeneic cell therapy applications.
- Gargi Roy M.Sc. - Associate Director, BioPharmaceuticals Development, AstraZeneca
- Kalle Johnson - Senior Director, UPSIDE Foods
This presentation will cover the points to consider for enabling multi-use systems in a Next Generation Biotechnology (NGB) facility. Multi-use systems improve operability while reducing cost and facility environmental impact. A framework for enabling multi use systems will be proposed including a review of batch definition, genealogies, hold times, product quality assessments, microbial control, compliance, validation, and regulatory considerations.
- Brian Gregory Youchak - Sr. Advisor, Eli Lilly and Company
- Andrew Zydney, Ph.D. - Bayard D. Kunkle Chair, Chemical Engineering, Penn State University
- Stefano Menegatti - Associate Professor, North Carolina State University
- Ohnmar Khanal, Ph.D - Downstream Technology Lead, Spark Therapeutics
- How do we define AI/ML?
- Which industries have already implemented AI/ML? How can the Biopharma industry learn from this?
- Is Biopharma prepared for this transition?
- Early adopter’s vs late adopters: Will there be any impact?
- How can small, mid-size, and large companies strategize for ML/AI implementation?
- Can it be beneficial for all areas of biopharmaceutical development (discovery, development, clinical and manufacturing)
- Cost reduction and accelerated timelines for project
- Amish Patel - SVP, Technical Activity Operations, Calidi Biotherapeutics
- David Lee - Executive Director, Analytical Chemistry, Mersana Therapeutics
- Monica Sadek - Technical Development Scientist 2, Protein Analytical Chemistry, Genentech
- Navigating diverse region-specific frameworks to expedite approvals.
- Build strategic partnerships with local distributors to facilitate market entry.
- Tailor marketing and patient education strategies
- Collaborating with local health services/distributors in preparation for product launch
- Ensuring preparedness for your supply/logistics chain across goal market
- E.g. Cryopreservation facility/availability when transporting
- Amish Patel - SVP, Technical Activity Operations, Calidi Biotherapeutics
- Ben Doak - National Senior Programme of Care Manager - Innovative Treatments, NHS England
- Nathan Lee - Senior Director, Gene Therapy CMC, Poseida Therapeutics
- Shashi Murthy, PhD - CTO and Co-Founder, Nanite Inc.