Thursday, September 26, 2024 - Day Three of Main ConferenceThursday, 26 September 2024 - ET (Eastern Time, GMT-05:00)

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 & Upstream 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

The automation of monoclonal antibody (mAb) production necessitates real-time information on the concentrations of products and contaminants at various process stages, which current analytical methods cannot provide. This presentation introduces a fiber-optic nanoplasmonic biosensor system designed for automatic, real-time affinity-based detection and quantification of Immunoglobulin G (IgG) and IgG aggregates. These sensor systems can be integrated into both upstream and downstream unit operations, offering specific biodetection in complex sample matrices with high sensitivity and selectivity across a wide concentration range. The flexible flow cells enable continuous monitoring at different production scales and flow rates, thereby simplifying process development, enhancing production, and facilitating process intensification and automation in mAb manufacturing.

• Automation and multiscale modeling can be integrated to accelerate purification development and aid in process understanding.
• Two mAbs with approximately the same isoelectric point had notably different loading and elution behavior in cation-exchange chromatography.
• Protein surface properties should be considered during development of chromatographic polishing steps, since isoelectric point does not tell the full story.

• What do we see as standards and regulatory science needs to increase adoption of advanced technologies?
• How can AI be incorporated into smart and advanced manufacturing?
• How can regulatory agencies and industry work together to make safe and smart manufacturing a reality?

Recent advancements in mRNA technology have enabled mRNA-based vaccine and therapeutics entering a new era in medicine, however, the availability of established production facility is still limited. While mRNA production is much faster and platform design is more desirable than conventional cell-based vaccine, the tech transfer could still be challenging, especially across the globe. Arcturus’ PMDA approved first self-amplifying mRNA COVID vaccine exemplifies this challenge. With numerous tech transfers, the endeavour has been both enlightening and enjoyable. We would like to share the journey of our global tech transfers, including the raw materials, process and assay tech transfers, and lost in translation situations.

Enhancing productivity and efficiency is essential for converting discoveries into viable treatments. Although the objectives during clinical phases differ from those in commercial manufacturing, their significance remains high. During clinical phases, the primary aim is to expedite processes without compromising quality. In contrast, commercial manufacturing focuses on consistent performance, high quality, and maximizing throughput, productivity, and yield to reduce the cost of goods (COGs). To achieve these goals, a comprehensive approach is necessary, incorporating various process technologies, materials, equipment, and analytical methods. This presentation will highlight how the selection and integration of bioreactor technologies, harvest techniques, purification processes, and analytical tools can synergistically improve productivity. We will showcase examples illustrating how these choices, combined with process design and optimization, lead to high levels of productivity and sustainability. Moreover, we will demonstrate that these strategies are applicable to both small and large-scale operations, including new and legacy facilities, as well as clinical and commercial manufacturing environments. By aligning process development with product design, significant productivity gains can be realized, ensuring efficient and cost-effective biopharmaceutical production.

• Co-mixtures add complexity to the assessment of product quality and potency
• Compromises may be required at the formulation stage to enable acceptable product quality/stability for each API
• Agency expectations with regards to stability profiles for the individual API’s within the co-mixture compared to as individual products
• Sorting through the impurity profiles in the co-mixture

Welcome To Group Therapy. Let's share the pain. Please join us and come prepared with your bioprocessing related problems. How it will work is we have 4 Round Tables each covering a different area of Bioprocessing. Each will be led by an expert. The expert will guide the discussion allowing participants to share their challenges and time to discuss within the group. These will last for 40 minutes. Included are some examples below:

Round Table Discussions

Cell Line Development & Upstream

• Expanding use of various cells: from Bacteria, yeast, and animal cell platforms to therapeutic cells
• The expanding nature of products: from therapeutic cells, to peptides, proteins, nucleic acids, and viruses
• Upstream sustainability: defining clear goals, establishing unambiguous metrics. and evaluating available options
• Upstream implications of AI: from process control, to supporting personalization, to heightened PAT, to continuous process verification
• Process intensification: Tools for increasing final product yield per cost, time, volume, footprint, personnel, and environmental burden generation
• Process, equipment, and suite flexibility: considering specific goals, performance and financial costs, and the various tools and solutions available

Recovery & Purification

• Standards and Validation: Meeting regulatory requirements and documenting processes for quality assurance
• Product Stability: Maintaining product integrity is essential for safety and efficacy. Degradation or aggregation can compromise the biologic's effectiveness and lead to safety concerns
• Yield & Efficiency: High yield and efficient recovery are crucial for the economic viability of the production process. Low yield or inefficient processes can significantly impact the cost and scalability
• Impurity Removal: Effective removal of impurities is vital to ensure product purity and safety. This includes removing contaminants like host cell proteins, endotoxins, and residual nucleic acids
• Cost and Time: Balancing cost and time with quality is essential for commercial success. High costs or prolonged production times can affect the economic feasibility of the biologic
• Solubility and Precipitation: Maintaining protein solubility and managing precipitation issues

Innovation & Adaptation:

• Compliance: Ensuring that new processes comply with existing regulations and standards can be challenging
• Compatibility: New technologies must integrate seamlessly with existing systems and workflows, which may require significant adjustments
• Data Integration: Managing and integrating data from new systems with legacy systems can be complex
• Economic Justification: Demonstrating the return on investment (ROI) and economic benefits of adopting new technologies
• Operational Disruption: Implementing new technologies can disrupt existing processes and workflows
• Cultural Resistance: Overcoming resistance to change within the organization

Cell & Gene Therapies

• Approval Processes: Lengthy and complex approval processes for new therapies
• Production Scale-Up: Difficulty in scaling up manufacturing processes from lab to commercial scale while maintaining consistency and quality
• Batch-to-Batch Variability: Managing variability between production batches
• Economic Viability: Demonstrating cost-effectiveness and economic viability for widespread use
• Material Sourcing: Securing reliable sources of high-quality raw materials and reagents
• Cold Chain Logistics: Maintaining cold chain logistics for sensitive products
• Customization: Customizing therapies for individual patients, which complicates standardization and scalability
• Long-Term Safety: Monitoring and ensuring the long-term safety of patients receiving cell and gene therapies
• Off-Target Effects: Minimizing off-target effects and unintended consequences of gene editing
• Advanced Analytics: Employing advanced analytics to develop and validate robust assays for measuring potency, purity, and safety.

• How do you avoid greenwashing and ensure your efforts are viewed as credible? What role does third-party verification play in that?
• What are the key needs and goals of pharma and biopharma laboratories when it comes to sustainability?
• Biotechnology and pharma are among the world’s largest carbon-emitting industries. What steps need to be taken in the future to lower their position in this list of carbon emitters?
• What are the most significant challenges or barriers that the pharma industry faces in implementing more sustainable practices?
• Renewable energy purchasing and PPA's
• The health sector generates four to five percent of total global emissions
  • Mainly to do with the supply chain and the impact from globally shipping
  • Challenges in contract manufacturing and M&A
  • Focus on Scope 3 and how to address it: What is one cool industry collective action initiative
  • Focus on product development (80% for design for sustainability), going upstream
  • Complex global value chain- need to work together to solve sustainability and create circularity.

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

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.

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.

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.

Explore our other tracks to curate your ideal conference experience, and discover exciting new content that sparks your curiosity!

• Can AI-ML benefit all stages of biopharmaceutical development (discovery, development, clinical, and manufacturing)?
• How can data quality and integrity concerns be addressed in AI-ML applications?
• How can companies ensure adherence to regulatory standards when employing AI-ML technologies?
• What cultural factors affect the acceptance and adoption of AI-ML within an organization?
• How crucial are collaborations and partnerships in driving AI-ML progress in biopharmaceutical manufacturing?
• How would you recommend an AI/ML novice gets started?