Agenda
07.35 – 08.20
Registration
08.20 – 08.30
Welcome & Chairman’s Opening Remarks for Day One
Tom Ransohoff, Operating Partner, Keensight Capital
08.30 – 09.00
- Merck has a drug substance manufacturing platform for biologics with state-of-the-art facilities that prioritize green and sustainable practices.
- Technological advances are integrated to manage the complexity of next-generation biologics.
- Platform fit for the non-platform molecules are discussed in case studies.
Shuangping Shi, Associate Vice President, Head of Biologics Process Research & Development, Merck
09.00 – 09.30
Case studies, with a focus on non-mAb modalities, will be shared on the following topics related to biologics downstream process development:
- High-throughput screening and automation for increased speed, productivity, efficiency, sustainability
- Monte Carlo simulation-based facility fit analysis for decreased GMP production costs
- Multi-column capture chromatography for decreased GMP production costs
- Use of prior knowledge management tools for increased speed and efficiency.
Angela Lewandowski, Sr. Director | GDPE (Global Downstream Dev/Pilot Plant/External Mfg), Bristol Myers Squibb
09.30 – 10.00
- NGM manufacturing and Next Generation Data Systems
- From Product Specific Recipes to Multiproduct Generic Recipes
- Impact on Tech Transfers
- Implications for Subject Matter Experts and development of skillsets
Downstream Development
Process Characterization and Control Strategy Platform Development
- Accelerated clinical process development and CMC timeline
- Downstream process characterization workflow and case study
- Leverage prior knowledge to simplify process characterization design
- Approach on downstream Tier 1 and Tier 2 process characterization to enable PPQ and BLA
- Control strategy platform development for robust manufacturing
- Modelling consideration on future process characterization
Lihua Yang, Principal Research Scientist II, AbbVie
Upstream Sciences
Transforming traditional cell culture process development with insilico solutions
- Establishing a generic insilico model for cell culture processes.
- The impact of generic models on cell culture productivity and quality over multiple programs.
- Can Insilico modelling significantly improve process development over traditional approaches?
- What gains can we achieve by applying insilico modelling to early or late-stage programs?
Sarwat Khattak, Head of Cell Culture and Cell Line Development, Biogen
For 6 to 10 participants (per roundtable) to discuss and debate on a topic of their choice
1. Addressing Upstream Bioprocessing Complications
2. Optimizing Cell Line Development for Next Generation Biologics
3. Downstream Process Development Strategies for Effective Bioprocesses
4. How MSAT Drives Efficient Tech Transfer. Innovative Solutions For Bioprocessing Challenges
5. Delivering Fast, Flexible, Reliable Manufacturing Leveraging Automation and Digital Technologies
6. Next Generation Bioprocess Facility Design
7. Latest trends in Integrated Continuous Bioprocessing
8. Challenges in Outsourcing CMC development
- Downstream/Upstream Process Technology Platforms
- Biopharma 4.0
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Separation and Purification Technology
- Virus Filtration Processes
- Smart Manufacturing Technologies – Tech. Transfer
- Facility Management & Integration
- Biopharma & Modular Biosafety Technology
- Capacity & Facility Design
- Multi product facilities
- Fluid Management Systems
- Lean/Operational Excellence
- Continuous Improvement
- PAT & MES, Automation and Process Control Excellence
- QbD, Quality Assurance & Quality Systems
- Validation Process/Life cycle Management systems
- Regulation – Rapid Release Testing
- cGMP – Contract, External Manufacturing Services
- Biogenerics/Biobetters
- Personalised Medicines
- Cell & Gene Therapy
- Fill and finish
- Microbial Process Development and Production
- Osmolality testing
- Bioprocessing Osmometers
Introducing the next cycle of affinity resin innovation
- The bioprocessing industry is continually challenged to increase productivity while keeping the cost of goods down when developing the next generation of
therapeutics. One key aspect of the downstream purification process is the capture step, which relies upon protein A chromatography resins. - Purolite, an Ecolab company, will present its next-generation high-capacity protein A resin that demonstrates improved stability with low ligand leakage.
The resin aims to increase productivity and cost reductions. Building on the success of Praesto™ Jetted A50 HipH, this protein A continues to address aggregation
and impurity clearance through a wider pH elution window.
Implementing PUPSIT Using Single-Use Systems for Final Fill
- For manufacturers who cannot terminally sterilize their product in its final container and require sterile filtration, the revised Annex 1 means that Pre-Use Post-Sterilization Integrity Testing (PUPSIT) has become a default requirement.
- This presentation is intended to explore the current thinking regarding the implementation and integration of PUPSIT for organizations utilizing Single-Use Systems (SUS) in final fill operations.
New Bioprocess Strategy with Fiber Chromatographic Clarification Platform from Discovery to Manufacturing
- We will explore how novel clarification technology, based on advanced synthetic fibrous chromatography materials, will enable new bioprocess strategies to address critical challenges in process simplification and intensification.
- We will illustrate how this platform can offer seamless implementation of chromatographic clarification from discovery to clinical and commercial manufacturing, providing consistent and high-quality clarified fluid and enhancing commercialization productivity.
Downstream Development
Enhancing Aggregate Reduction using Anion Exchange Hybrid Filter in an Immunocytokine Diabody Fusion Protein Purification Process
- Unique aggregation challenge was presented by a diabody fusion protein
- Anion exchange hybrid filter (EmphazeTM AEX) showed significant aggregate reduction
- ~ 25% aggregate reduction at harvest clarification step
- Aggregate binding mechanism was elucidated to be electrostatic binding
Jian Ren, Principal Scientist, AbbVie
Upstream Sciences
Cell culture automation and risk-based levers to accelerate DNA to IND
- Balance of timeline, business risk, and pre-investment to accelerate FIH timeline
- Cell line development strategies to enable earlier delivery of material for exploratory and IND-enabling Tox studies
- High-throughput tools for automating clone/process screening and bioreactor sampling
- Data automation connectivity for real-time capture and visualization of bioreactor metrics
Kyle McHugh, Associate Director, Takeda Pharmaceuticals
Novel PAT and data science tools in inclusion body processing
- Spectroscopic tools to monitor IB processes
- Data driven models for IB processing
- Process understanding
- Digitalization
Ionela Iliescu, Sr. Scientist, Biogen
Troubleshooting growth rate variability between media bottles in a commercial protein therapeutic biomanufacturing process utilizing human embryonic kidney (HEK293) cells
- This case study examines a situation in which growth variability was observed in the early stages of a commercial manufacturing process. Poor cell growth resulted in process failure as insufficient cells were present to inoculate future stages.
- Laboratory studies indicated that the media was the cause of the variability, and that performance differences were present between bottles of the same preparation.
- Further experimentation determined that the media pre-filter was the cause of the variability between bottles, and the mechanism of action was determined to be the removal of a media component via adsorption to the filtration membrane.
- This saga resulted in a re-evaluation of filter risk assessment strategy within Biogen, as approaches which were found to be successful with one cell line were not necessarily best fit for another.
Brandon Moore, Senior Engineer, Upstream Process Sciences, Biogen
Elucidating the Influence of Antibody Surface Charge Heterogeneity in Cation-exchange Polishing with High-throughput Techniques and Multiscale Modeling
- 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.
- These molecules had differences in surface charge density in the antibody CDR region, which was directly tied to the screening outcomes
- Protein surface properties should be considered during development of chromatographic polishing steps, since isoelectric point does not tell the full story
There Is No Free Lunch: Building Advanced Analytics for Commercial Biomanufacturing
- Advanced analytics as an enabler for biomanufacturing lifecycle management
- Build vs Buy: where and when
- Getting to the data: extraction, contextualisation, pre-processing and integrity
- Who is consuming data in the organisation and what do they need?
- Moving from data to insights and from insights to actions (case study)
Alexandre Super, Lead CMC Statistician, UCB
- Downstream/Upstream Process Technology Platforms
- Biopharma 4.0
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Separation and Purification Technology
- Virus Filtration Processes
- Smart Manufacturing Technologies – Technology Transfer
- Facility Management & Integration
- Biopharma & Modular Biosafety Technology
- Capacity & Facility Design
- Multi product facilities
- Fluid Management Systems
- Lean/Transformational Change – Operational Excellence
- Continuous Improvement / Manufacturing Processing
- PAT & MES, Automation and Process Control Excellence
- QbD
- Quality Assurance & Quality Systems
- Validation Process/Life cycle Management systems
- Regulation – Rapid Release Testing
- cGMP – Contract, External Manufacturing Services
- Biogenerics/Biobetters
- Personalised Medicines
- Cell & Gene Therapy
- Fill and finish
- Microbial Process Development and Production
- Osmolality testing
- Bioprocessing Osmometers
Amsphere A+: the new Protein-A affinity resin with high DBC and outstanding 1M NaOH stability
- Protein A chromatography is the most common form of affinity chromatography used in the biomanufacturing of monoclonal antibodies and there are many commercially available PrA resins on the market.
- In 2016, JSR launched Amsphere A3, which gained tremendous momentum in being implemented in >150 clinical and commercial purification processes. The new Amsphere A+ further leverages the great science behind JSR’s PrA-resins and provides even better DBC, caustic stability and pressure-flow performance compared to A3.
- A look on the development journey of and the science behind Amsphere A+ and compare the characteristics and performance of it with other established PrA resins.
Double the yield of perfusion processes: Process intensification & simplification with Vibro® Membrane Filtration (VMF)
- VMF – Revealing new opportunities for upstream & downstream processes
- Novel cell retention device – Higher cell density, less membrane fouling
- Eliminate process steps such as centrifugation, high speed separator
- Sustainable development and production – 90% reduced energy consumption
The Quest for the Golden Batch in BioPharma 4.0
- Batch Release Software- How to Capture Data Directly from Batch Engines
- How to gain real-time visibility into batch status and enable faster decision making
- Optimize Yield, Quality, Efficiency and Revenue with the latest Batch historian Software
- Reduce Process Variability and Improve Product Consistency and Quality Control
- A vision and roadmap for implementing digital and automation technologies to improve KPI’s (Speed, Productivity and Sustainability) including ESG goals for in-process analytical testing during process development of biologics.
- Automation strategy for in-process analytics going beyond typical liquid handlers. This includes SCARA and mobile robots for sample handling, preparation, and logistics.
- Case Study # 1 – A modular mini lab featuring end-to-end and fully automated analytical testing platform.
- Digital infrastructure including robotic process automation (RPA), data management and Machine Learning.
- Case Study #2 – “Digital worker” for data automation using RPA BOTs.
- Case Study #3 – Leveraging Machine Learning Predictive Models for Rapid Method Readiness in Process Analytics
Dhanuka Wasalathanthri, Associate Director, Bristol Myers Squibb
Networking drinks reception
CHAIRPERSON’S OPENING REMARKS FOR DAY TWO AND SUMMARY OF DAY ONE
- Applying advanced data analytics to gain additional process and product understanding, improved process control, and process performance
- Upstream process case study to improve upstream productivity and process robustness is discussed
Daryl Powers, Ph.D., Director, Bioprocess Technology Manufacturing Science and Technology, Bristol Myers Squibb
08.50 – 09.20
Autoantigen-specific IgA autoantibodies closely correlate with symptoms severity in a subgroup of patients in multiple autoimmune diseases. Beyond the value of these IgA autoantibodies as biomarkers, the presence of excessive IgA/autoantigen immune complexes results in continuous CD89 (Fc?RI)-mediated activation of myeloid cells, leading to severe tissue damage. Activation of myeloid cells – especially of neutrophils – is a highly underappreciated and untargeted hallmark of autoimmune diseases. Enabling a personalized medicine approach, high autoantigen-specific IgA serum levels will serve as companion diagnostic to stratify patients for personalized treatment with our antagonist humanized anti-CD89 antibody (JJP-1212). Interfering with the IgA/CD89 axis by JJP-1212, resolves IgA/autoantigen-induced inflammation and subsequent tissue damage in a variety of autoimmune diseases.
Bioprocess Innovation
The minimum requirement on PAT’s success for industrial implementation: The simultaneous prediction of multiple relevant Product Quality Attributes in real-time
- Raman-based PAT
- Multi-attribute measurement
- In-line quality monitoring
- Machine learning methods
Carrie Mason, Associate Director Bioprocess R&D, Lonza
Digitalization
Applications of Cell Culture Digital Twins in Fed-Batch and Perfusion Processes
- Developing a digital twin for cell culture processes
- Impact of digital twins in process scale-up
- Applications of digital twins in perfusion processes
- Opportunities for the future
Brooke Tam, Process Engineer IV, Sanofi
Comparability studies to support manufacturing process change, enhancing product quality and accelerating timeline to commercial launch
- Introduction of patient centric comparability
- Risk assessment of process change and comparability study
- Case studies of comparability study to enable product quality improvement and acceleration
- Regulatory feedback for novel strategies
Dr Wenqin Ni, Senior Principal Scientist, Pfizer
Enhancing Biologics Manufacturing Efficiency through Data Science: Insights from Case Studies
- Overview of the role of data science in enhancing manufacturing efficiency and product quality in the biopharmaceutical industry.
- Case study 1: Predictive Modeling in Cell Culture
- Description of the cloud-based predictive modeling application for forecasting bioreactor potency.
- Discussion of the methodology used to quantify prediction uncertainty and its implications for process control.
- Case Study 2: Drug Product Potency Target Evaluation
- Introduction of the novel framework for assessing out-of-specification (OOS) risk in drug product potency.
- Explanation of the cloud-based statistical software application developed to streamline potency target evaluations.
Shyam Panjwani, Principal Data Scientist, Bayer Pharmaceuticals
For 6 to 10 participants (per roundtable) to discuss and debate on a topic of their choice
1. Addressing Upstream Bioprocessing Complications
2. Optimizing Cell Line Development for Next Generation Biologics
3. Downstream Process Development Strategies for Effective Bioprocesses
4. How MSAT Drives Efficient Tech Transfer. Innovative Solutions For Bioprocessing Challenges
5. Delivering Fast, Flexible, Reliable Manufacturing Leveraging Automation and Digital Technologies
6. Next Generation Bioprocess Facility Design
7. Latest trends in Integrated Continuous Bioprocessing
8. Challenges in Outsourcing CMC development
- Downstream/Upstream Process Technology Platforms
- Biopharma 4.0
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Separation and Purification Technology
- Virus Filtration Processes
- Smart Manufacturing Technologies – Technology Transfer
- Facility Management & Integration
- Biopharma & Modular Biosafety Technology
- Capacity & Facility Design
- Multi product facilities
- Fluid Management Systems
- Lean/Transformational Change – Operational Excellence
- Continuous Improvement / Manufacturing Processing
- PAT & MES, Automation and Process Control Excellence
- QbD
- Quality Assurance & Quality Systems
- Validation Process/Life cycle Management systems
- Regulation – Rapid Release Testing
- cGMP – Contract, External Manufacturing Services
- Biogenerics/Biobetters
- Personalised Medicines
- Cell & Gene Therapy
- Fill and finish
- Microbial Process Development and Production
- Osmolality testing
- Bioprocessing Osmometers
Sustainability in Biomanufacturing: Leveraging Continuous Processing and Advanced Single-Use Technologies
- Biomanufacturers are being challenged to balance the development of new therapeutic modalities and reducing manufacturing costs while maintaining environmental responsibility.
- Efforts are underway to improve process robustness and efficiency and create more flexible manufacturing facilities.
- Key strategies include adopting single-use technologies, implementing process-intensification and continuous manufacturing strategies, enhancing process analytics, and developing digital capabilities to leverage artificial intelligence (AI) in development and manufacturing.
- Collaborative projects addressing these issues through new chromatographic solutions will be presented.
Buffer management strategies: how to stay nimble and competitive in biologics manufacturing
- Holistic approach to buffer management, discuss the known and unknown challenges, and consider different options of buffer preparation, weighing the merits of in-house vs. outsourcing.
- Conceptual design scenarios in both existing and new facilities will be shared to assist with the economics and logistics of the buffer journey.
- How the best buffer management approaches come together to deliver significant operational benefits —allowing biologics manufacturers, including CDMOs, to remain nimble and competitive
Forget about Isolators: High Accuracy for Automated Small Volume Filling
Automated and standardized aliquoting of biopharmaceutical drug substances into single-use bags simplifies the manufacturing process while improving throughput, speed, and filling accuracy. Learn how Single Use Support took pride in developing breakthrough technologies for a customer to improve fluid management processes. The groundbreaking automated filling platform helped eliminate the need for isolators and standardize the aliquoting of small volumes of biopharmaceuticals to meet
- GMP Annex 1 requirements
- Cost-efficiencies in the fluid management process (OPEX/CAPEX)
- Unprecedented filling accuracy and speed
Process Transfer/Analytical Development
Development of a 10 g/L process for a difficult-to-express multi-specific antibody format using a holistic process development approach
- The presentation provides an example on how to overcome expression limitations of bi- and multispecific antibodies in a holistic approach, using tools of molecular biology, cell line development, upstream process optimization and process intensification.
- The combination of molecular constructs described in this article allows very high expression levels, which is highly useful for difficult-to-express proteins
- Process allowing titers > 10 g/L (product) for bi- and multi-specific antibody formats
Bioprocess Innovation
Debottlenecking of a tangential flow filtration process for high concentration monoclonal antibody formulation
A significant yield reduction with associated flux decay and was experienced while scaling up a mAb process to manufacturing scale due to gel layer build-up during a TFF process execution. In a fast-track approach, the challenges with increased viscosity and yield reduction were mitigated using a model protein/ molecule and changes in process and material re-design.
Application of Plant and Process Models from Development to Commercial Facility
- Models as digital solution to address process and facility related challenges
- Case studies of applying plant & cost models for e.g., transfer and debottlenecking activities
- Creation and utilization of holistic USM & DSM plant models for manufacturing facilities
- Optimization of model capabilities and integration into workflows
Elucidating the Influence of Antibody Surface Charge Heterogeneity in Cation-exchange Polishing with High-throughput Techniques and Multiscale Modelling
- Automation and multiscale modelling 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 behaviour in cation-exchange chromatography
- These molecules had differences in surface charge density in the antibody CDR region, which was directly tied to the screening outcomes
- Protein surface properties should be considered during development of chromatographic polishing steps, since isoelectric point does not tell the full story
- Solving the challenge: an automated lab which combines all elements of bioprocess development
- Self-driven model-based bioprocess development is possible
- Scalability from high throughput stations to industrial scale is a major issue which can be verified through parameter identification
- FAIR data is not only the key of all autonomous operations be also for integrating collaboration into a HT facility.
Please Note: Workshop, Agenda, Speakers and Participants can be subject to change