Agenda
DAY ONE
07.45 – 08.30
Registration
08.30 – 08.40
Welcome & Chairman’s Opening Remarks for Day One
Nihal Tugcu Global Head of Mammalian Platform Process Development and Clinical Manufacturing, Sanofi
08.40 – 09.10
Biopharmaceutical manufacturing – accelerating the path from concept to market (to patient)
- The last decade has seen a rapid transition in therapeutical formats: from small molecules to complex proteins (mono-, bi- and multi-specific Abs), to nucleic acids, and even more complex formats such as viral vectors.
- The increase in the degree of complexity is mirrored by the rise in druggable targets and promising discoveries that offer hope to diseases that were once thought to be untreatable.
- Many promising therapeutic approaches fail to reach the patient, although showing great potential in early discovery.
- To enable complex solutions, one must master the complexities of biopharmaceutical manufacturing at every step: tech transfer,process development, cMP production, right through to regulatory approval.
- To tackle today’s key challenge a holistic approach is needed that streamlines a therapeutic’s path from concept to market to patient
Mairead Looby, Executive Director MSAT, Bristol Myers Squibb
–
09.10 – 9.40
Strategy to develop and implement a Downstream Continuous Bioprocess with a fully integrated system for clinical manufacturing scale
- The equipment and automation supporting Next Generation Manufacturing (NGM) for downstream unit operations can be complicated and expensive. In this talk we present an integrated solution for chromatography column operation, viral inactivation with pH control, filtration and in-line dilution
- This solution can lead to significant reductions in facility size, manufacturing costs, and enhanced product quality when compared to the usual batch mode of operation, or the alternative to integrate many different pieces of equipment through a Distributed Control System (DCS) from different vendors
- Details of operation, for the duration of a perfusion run, with bioburden control are explained
- Implementation strategy for GMP manufacturing is presented
Irina Ramos, Director in Bioprocess Technologies & Engineering group, AstraZeneca
Downstream Processing
09.45 – 10.15 Bench-scale assay for disulfide reduction of antibodies and charged filter as an at-scale mitigation tool
- Development of current mitigation strategies including platform alignment, mitigation strategy application for bi- and tri-specific antibodies and using machine learning to identify molecule susceptibility of disulfide bond reduction
Hendri Tjandra, Head of Purification and Isolation, Bayer
Upstream Processing
09.45 – 10.15 Superior cell culture performance through rational media design
- Continuous improvement of chemically defined media for efficient and robust antibody production of CHO cell lines
- Enhanced media insights from metabolic and in silico methods
- Enabling high titer, high viability process starting from FIH
- Media design and feeding strategy modulation to target productivity and product quality
Dr. Sarwat Khattak, Head Of Cell Culture Development, Biogen
10.15 – 11.05
COFFEE BREAK & MEETINGS
11.05 – 11.35
Using mechanistic modeling to accelerate design and facilitate regulatory approval
- Overview of recent advances in mechanistic modeling of bioreactors to achieve optimal yield, shorter cycle time and robust operation
- Evaluation of hybrid modeling for the design and optimization of downstream purification processes
- Discussion of the role of a mechanistic approach in regulatory approval
11.40 – 12.40 One to One Meetings
- Downstream/Upstream Process Technology Platforms
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Biopharma Hygienic Diaphragm Valves
- 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
- Downstream process (auxiliary aids or ingredients for processing aids) and fill/finish formulation (excipients as stabilizers
11.40 – 12.10 The “why and how” behind the rapid growth and development of single-use biopharmaceutical manufacturing
- Facility Automation/Communication – Decentralized, Distributed & Centralized Automation
- Gas control in Fermentation
- Industry trends and growth metrics
- Defining Multi-Use Stainless, Multi-Use Plastic and Single Use
12.10 – 12.40 Accelerating upstream process development with direct CQA and media analysis feedback
- Informed decisions are made faster by consolidating at-line CQA and culture media analytical testing, with the combination of Sartorius Ambr 15 and Waters BioAccord LC-MS systems.
- Day-to-day changes in CQAs, like glycosylation, and the impact of process parameter variations can be tracked at-line by process engineers.
- Close-coupled feedback allows CQAs to drive process parameters.
- Cell culture media are analyzed at-line throughout clone selection and process development activities.
- Statistical analysis tools can be applied to gain insight on key metabolic changes.
12.40 – 13.30
NETWORKING LUNCH
Downstream Processing
13.30 – 14.00 Inline harvest adjustment and salt precipitate removal in a continuous biomanufacturing process
- Developed an integrated and continuous process for clinical manufacturing of a complex, novel protein modality for first-in-human studies
- Performed small-scale studies to understand challenges and key parameters of harvest adjustment and precipitate removal
- Implemented automation to enable upstream and downstream integration, facilitate continuous operation, and minimize harvest hold time
- Successfully scaled up harvest adjustment and filtration operations to clinical manufacturing scale
- Demonstrated microbial control and consistent product quality over campaign duration
Crystal Thomas, Scientist, Sanofi
Upstream Processing
13.30 – 14.00 Global automation standards for rapid and scalable process analytical technology development and implementation
- Establish robust cell line specific models using Raman spectroscopy and DoE for scalable automated bioreactor control
- Harmonize platforms across sites globally and across scales to streamline process scale up with automation
- Utilize automation from laboratory scale (1L) to Pilot scale (250L) for Raman and Capacitance based feeding in an intensified process
- Establish harmonized control and open system architecture across global sites
Brian Hadley, Lead Scientist R&D Upstream, Lonza
14.00 – 14.30 Leveraging Non-platform Tools to Control HMW During the Purification of a Bi-specific DVD Protein
- The DVD protein is a poorly behaved molecule during downstream purification.
- Tight %HMW spec was set at BDI stage, in order to achieve target purity in final BDS post conjugation.
- Non-platform purification options, such as harvest RC filter, CEX conditions and UF/DF screens were evaluated to achieve HMW control.
- Process successfully transferred to 500 L pilot scale.
Lei Cao, Principal Scientist, Purification Development, Abbvie
14.00 – 14.30 A novel way of approaching upstream process characterization and optimization using multi-phasic modelling techniques
- DoE and RSM methods are useful tools for upstream bioprocess optimization and characterization
- Fed-batch cell cultures are multi-phasic (i.e. having growth and production phases) but traditional RSM methods employ static set-points
- The use of dynamic set-points provides a unique response in upstream cell culture which static set-points do not provide
- The use of a dynamic RSM method has been demonstrated to improve cell-specific productivity and titer in upstream cell culture relative to traditional RSM method
Brandon Moore, Senior Cell Culture Engineer II, Biogen
14.35 – 15.05
Smart Process Analytics for the End-to-End Batch Manufacturing of Monoclonal Antibodies
For many modern biopharmaceutical processes, manufacturers develop data-driven models using data analytics/machine learning (DA/ML) methods. The challenge is how to select the best methods for a specific dataset to construct the most accurate and reliable model. This article describes the application of smart process data analytics software to industrial end-to-end biomanufacturing datasets for monoclonal antibody production to automate the determination of the best DA/ML tools for model construction and process understanding. The application demonstrates that smart process data analytics software captures product-and process-specific characteristics for two different monoclonal antibody productions. This study provides tools that can be widely applied to biomanufacturing processes for root cause analysis, prediction, and control.
Prof. Richard D. Braatz, Edwin R. Gilliland Professor of Chemical Engineering, MIT
15.05 – 15.55
COFFEE BREAK & MEETINGS
15.55 – 17.25 One to One Meetings
- Downstream/Upstream Process Technology Platforms
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Biopharma Hygienic Diaphragm Valves
- 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
- Downstream process (auxiliary aids or ingredients for processing aids) and fill/finish formulation (excipients as stabilizers
15.55 – 16.25 Optimizing Harvest and Recovery with Single Step Depth Filtration
- Filter and diatomaceous earth selection
- High throughput screening at 20ml sample size
- Scalability from 0.1L to 2,000L+
- Scale-up for pilot and production
16.25 – 16.55 Advances in Protein A Chromatography Resins
- Jetting technology is a continuous emulsification technology by which all Praesto® chromatography resins are produced.
- This proprietary technology results in resins with a narrow, almost uniform particle size distribution, with excellent mass transfer properties.
- Herein, we present advances which utilize Jetting technology, including process intensification models and a novel Protein A resin designed specifically for elution of Fc-containing molecules at higher pH levels
16.55 – 17.25 Scalable Single-Use Platform for Intensified Downstream Processing
- Upstream Process Intensification places additional demands on Downstream Processing
- Cost-effective solutions for high cell density clarification
- Single-use, scalable Membrane Adsorbers can be easily adapted into connected/continuous DSP
- Extended-use Virus filters challenge traditional approach
- Scalable Single Use & single-pass TFF options will be discussed
17.25 – 17.55 CSL112 Process Characterization: a modern process development approach implementing QbD principles
- Implementing QbD principles for a plasma-derived biotherapeutic product
- Applying a risk- and science-based approach leading to the identification of process parameters potentially impacting quality and performance attributes
- Sequential DoE approach for process characterization: Pre-screening DoE followed by high resolution DoE
- Process performance analysis followed by statistical model building and Monte Carlo simulation to predict and minimize defect rate
- Outcome of process characterization leading to final classification of process parameters
- Thorough process understanding leading to a robust process control strategy
Madlene von Känel, Manager Bioprocess Development, CSL Behring
17.25 – 17.55 Overview of Analytical Control Strategy and Life Cycle Management for Biologics Products
- Analytical control strategy (ACS) and life cycle management of analytical methods play a significant role in Biologic drug product development.
- Knowing the complexity of Biologic products, effective ACS, and method life cycle are critical elements to delivering quality products with intended efficacy.
- The presentation will focus on the Overview of control strategy, Integrated control strategy and Analytical method life-cycle management
Udayanath Aich, Scientific Director, Bristol Myers Squibb
17.55 – 18.25
Open Panel Discussion:
Taking Bioprocess Innovation and Applying them Successfully to Other Modalities
- Leveraging expertise in biologics to enable new modalities (gene therapy, cell therapy, etc.)
- What have we learned that can be applied directly?
- What are the unique challenges with viruses and allogeneic cell therapies?
- New technologies that improve biological understanding for manufacturing complex proteins (PAT tools, real time monitoring)
- Have these proven useful? What are the gaps and opportunities?
Panel Members:
Kenneth Green, MSAT/Manufacturing Operations, Vertex
Sujit Jain, Director, External Manufacturing, Salio Gen Therapeutics
Shengjin Jin, Sr Director, Gene Therapy MS&T, Sarepta Therapeutics
Christina Alves, Head of US Biologics Process Development, Takeda
18.25
CHAIRPERSON’S CLOSING REMARKS AND END OF DAY ONE
18.30
Networking drinks reception
DAY TWO
08.30 – 08.40
CHAIRPERSON’S OPENING REMARKS FOR DAY TWO AND SUMMARY OF DAY ONE
08.40 – 09.10
Ensuring virus filtration scalability and optimal performance in manufacturing
- Scale-up and tech transfer of virus filtration from pressure-driven small-scale studies to single-use, pump-driven, large-scale manufacturing processes present many challenges
- Planova™ virus filters demonstrate excellent scalability of both performance and virus removal
- Pump-based virus filtration operations maintain the same high level of performance observed in small-scale studies even with different pump-types, control strategies, and with exaggerated pressure fluctuations
- Automation of virus filtration can be utilized to ensure optimal performance while maintaining reliable, predictable outcomes
Next Gen Manufacturing
09.10 – 09.40 Advancing Process Development Through Automation, Predictive Modelling, Process Intensification
- Concepts for acceleration of bioprocess development
- Automation of upstream process development with the end goal for process analytical technology integration
- Development and application of predictive modelling
- Development of an intensified process for next generation platform
Yang Yang, Director, Process Development, Takeda
CGT Innovation
09.10 – 09.40 Leveraging advanced phase imaging technology to monitor and control expansion of Allogeneic CAR-T cells in stirred tank bioreactors
- Current challenges with Allogeneic CART-T cells expansion and production processes
- Novel PAT solutions, integrated with advanced culture systems, to achieve automated, in-line, and continuous sampling
- Novel applications for performing online monitoring in stirred tank bioreactor cultures
- Detecting populations of allogeneic CAR-T cells in static and suspension formats and performance on par with standard offline measurement tools
Meena Narayanan PhD, Process Development Scientist, Poseida Therapeutics, Inc
Julian Kopelove, Process Development Associate II, Poseida Therapeutics, Inc
09.40 – 10.10 Role of modern SCADA software in today’s bioprocess development lab.
- SCADA as the central hub for digital lab connectivity
- Interfaces to and from SCADA to Data Science
- Key Elemental Design
Mehdi Saghafi, Principal Biotech Data Engineer, Bayer
09.40 – 10.10 Development, scale-up and manufacture of RNA therapeutics
- Overview of CPI RNA therapeutics capabilities
- Focus on development, scale-up and manufacture of RNA therapies and establishing a mammalian cell-based assay to analyse different RNA material
10.10 – 10.30
COFFEE BREAK & MEETINGS
10.30 – 11.15
Roundtable Discussions
For 4 to 8 participants (per roundtable) to discuss and debate on a topic of their choice
1. Accelerating upstream process development and scale up
2. Cell culture performance by rational media design and single-use bioreactors
3. Downstream process development strategies
4. Driving biopharma innovation – Sustainability and the future of bioprocessing and manufacturing
5. Virus filtration scalability
6. Digitalisation and automation for acceleration of bioprocess development
7. Effective technology transfer in CMC development
11.15 – 12.45 One to One Meetings
- Downstream/Upstream Process Technology Platforms
- Digitalization
- Specialised cell culture media
- Single-use & Disposable Technologies
- Biopharma Hygienic Diaphragm Valves
- 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
- Downstream process (auxiliary aids or ingredients for processing aids) and fill/finish formulation (excipients as stabilizers
11.15 – 11.45 Analytical Methods for the Release and Characterization of RNA-based Cell and Gene Therapy Products
As RNA-based vaccines and cell and gene therapy products have become more prevalent, there is an increasing demand for sensitive and robust methods for the analysis of the quality, safety, and potency of the product. To support release and characterization testing of RNA products, we have developed methods for determining:
- Process- and product-related impurities including RNA product size, ds RNA levels, residual DNA, and quantitation and identification of residual protein
- The efficiency of mRNA 5’ capping, identification of 5’ cap species, and length of the Poly-A tail
- The sequence of small RNA oligonucleotides used as inhibitory RNA (RNAi) products by LC-MS. The structure of RNAi products are often modified to promote stability and/or provide cell tropism and cannot be sequenced by conventional Sanger sequencing methods to confirm identity
- Cell-based and cell-free methods for evaluating potency
11.45 – 12.15 Evolution of a Next Generation, High-Intensity Manufacturing Process
- System Overview
- System Evolution
- Key Accomplishments
- Microbial Control
12.15 – 12.45 Filling the gap between Downstream & Fill-Finish with scalable single-use technologies
- The advantages of bags over bottles for primary packaging
- Eliminate manual processes during substance filling
- Benefits of controlled plate-freezers for your product quality
12.45 – 13.35
NETWORKING LUNCH
Bioprocess Innovation
13.35 – 14.05 Upstream Process Analytical Technologies (PAT) for Process Monitoring and Control
- Capacitance to monitor and control cell density overtime to ensure consistent productivity over time.
- Raman to monitor and control cell culture metabolites and productivity.
- Process analytical technologies (PAT) such as capacitance measurement and Raman spectroscopy allow us to continuously monitor the critical process attributes to ensure a consistent process performance.
- Scale up challenges and implementation of PAT tools in upstream.
Misaal Patel, Senior Scientist, Merck
Scale up/Tech Transfer
13.35 – 14.05 Smart CMC: Accelerating time to clinic and market
- What is smart CMC
- Platforming early-stage development
- De-risking scale-up and manufacturing
- Late-stage optimization
- concurrent validation strategies and BLA
Siddhartha Shrivastava, Vice President, Head of CMC and Global Technical Operations, CUE Biopharma
14.05 – 14.35 Process Intensification technologies using In-line concentrators for High Titer mAb process
- As mAb titers are increasing, its straining downstream purification manufacturing technologies. One of the issues facing manufacturing is the ever increasing in-process volumes, due to increasing titers.
- In this case study we would look at comparative evaluation of Single Pass Tangential flow filtration (SPTFF) or In-line product concentrators technologies for the there management of in-process volumes for downstream process fit.
- Comparative evaluation of SPTFF technologies on in-process volume controls including process robustness and controlling parameters, product quality impact, manufacturing scalability and implementation is discussed.
Sanjay Nilapwar, PH.D., Principal Scientist/Group Leader, Abbvie
14.05 – 14.35 Strategic Outsourcing and Effective Tech Transfer in CMC Development
- The benefits and challenges with outsourcing CMC development and manufacturing of biologics
- Deciding when to outsource and when to manufacture in-house
- Best practices for partner selection
- Innovative & Phase Appropriate Process Development and Optimization
- Proactive GAP analysis and Risk Management
- Effective technology & knowledge transfer
Dharmesh Kanani, Director, Process Development, Biologics CMC, Teva
14.35 – 15.05
Co-culturing cell lines for efficient manufacture of multispecifics
- Multispecific manufacture is complex
- Co-culturing cell lines could reduce the complexity and reduce clinical development timelines
Dawn Eriksen-Stapleton, Principal Scientist, Pfizer
15.05 – 15.30
COFFEE BREAK
15.30 – 16.05
Open Panel Discussion:
With next gen manufacturing technologies and processes and strategies emerging what gains are being realised for profitability, productivity and quality in future facilities?
- Assessing the benefits and drawbacks of the latest manufacturing technology trends
- How Single-use equipment can help achieve performance improvements, both for downstream purification and for manufacturing productivity overall
- Process and Product Considerations for Flexible Manufacturing
- How Process Technology Platforms can be used to Optimize areas and parameters in upstream processing and automation opportunities to improve productivity and quality
- Process intensification strategies in USP and DSP shortening process time
16.05
CHAIRPERSON’S CLOSING REMARKS
16.10
CLOSE
Please Note: Workshop Agenda and Speakers can be subject to change