Although not a completely new approach, continuous perfusion cell culture has recently become an increasingly popular option for designing new recombinant protein production and other cell culture based bioproduction processes. There are several attractive benefits offered by perfusion. This sponsored session will feature recent results from insightful studies conducted at KTH Royal Institute of Technology in Stockholm, along with an update on efforts to develop superior chemically-defined cell culture media from Fujifilm Irvine Scientific.

Speakers:

Véronique Chotteau
Principal Investigator of the Cell Technology Group and Director of AdBIOPRO, Competence Centre for Advanced BioProduction by Continuous Processing
KTH Royal Institute of Technology

Tom Fletcher
Director – Process Development
FUJIFILM Irvine Scientific

In this joint session we will describe the advantages of using Novo Nordisk Pharmatech’s new GMP grade trypsin (TrypsiNNexTM) in 2D and 3D (BioNOCTM II macrocarriers) cell culture compared to available non-GMP cell dissociation enzymes. 

• 3D BioNOC II carriers and tide motion bioreactors for large scale manufacturing of cells will be introduced, along with a small-scale proof of concept method used in subsequent experiments to access cell growth and detachment in the carriers  
• Detachment, reattachment and growth after reseeding of the cells grown in two and three dimensional MSC stem cell and MRC5 cultures 
• Identification of optimal concentrations for 2D and 3D culture detachment  
• Comparison of adipogenic, chondrogenic and osteogenic differentiation 
• Confirmation of cell line identity post detachment from 3D carriers by surface marker characterisation 

Speakers:

Theis Guldbech
International Sales Manager
Novo Nordisk Pharmatech 

Geraldine Chiew
Senior Scientist Stem Cell Department
Esco Aster

Whether you are a process development scientist, or working in procurement, this session will address effective ways to help streamline media manufacturing, including rapid, small-scale non-cGMP media prototyping and proprietary media formulation outsourcing options. Learn ways to decrease logistical roadblocks, increase quality and simplify the journey from finalization of media performance to scale-up, including how to utilize media analytics to help optimize your prototyping formulation.

Speakers:

Chad Schwartz, PhD
Senior Global Product Manager for Proprietary Cell Culture Media Formulations
Thermo Fisher Scientific

Megan Gorczyca
Senior Product Manager
Gibco™ PD-Express™ Services & Early Phase Product Management
Thermo Fisher Scientific

An appropriate dissolved oxygen (DO) concentration in the culture medium is a key driver for high bioprocess yields. DO is determined by the oxygen supply to the bioprocess system and the oxygen consumption of the cultured microorganism simultaneously. In high-density fermentation of aerobic bacteria and fungi, for example, a large amount of oxygen must be introduced into the medium to avoid oxygen limitation during robust microbial growth. In other applications, like the cultivation of microaerophilic bacteria for probiotics production or gut microbiome research, the DO concentration must be controlled precisely at a low level. In this webinar, we showcase advanced strategies to control the dissolved oxygen concentration in the culture medium and to reproduce it at different scales.

Key Learning Objectives:

• Importance of bioreactors’ oxygen transfer capabilities for bioprocess scale-up
• Method for measuring the oxygen transfer rate (OTR) of a bioreactor
• Hands-on expertise on how to optimize oxygen supply in high-density fermentation processes
• Hands-on expertise on how to establish microaerobic conditions for lactic acid bacteria bioprocesses

Speaker:

Ying Yang
Senior Research Scientist, Bioprocess
Eppendorf Inc.

Session Description TBD

Speaker:

Karthik Balakrishnan
CEO
Nodexus

Biotherapeutics can fail to be approved for reasons other than lack of efficacy or toxicity. In fact, failure can occur for reasons unrelated to a drug’s mechanism of action or efficacy, for example issues with the cell line or in process development.

Adding further to the challenge of successfully completing cell line and process development is the ever growing range of different molecule types under investigation. Although antibodies currently still dominate clinical pipelines, a shift is being seen in drug development towards more complex, next generation molecules. These molecules can include engineered elements not previously seen in nature and as a result, may not express well in current expression platforms. To achieve success, it is critical to get cell line development right, first time, regardless of the molecule type.

In this presentation we will discuss:

• (i) Different cell line development approaches to consider for different molecule types
• (ii) Technologies included in our GS Toolbox which are designed to help overcome challenges with next generation molecules, for example GS piggyBac®

Speaker:

Dr. Alison Porter
Head of Expression System Sciences
Lonza

The accelerated rate of advancement in downstream bioprocessing is largely driven by the increased need for improved biotherapeutics. Continuous bioprocessing, specifically, is becoming more widely adopted in biomanufacturing, and companies are exploring various ways the implementation of this technology can help them efficiently produce high quality products. As continuous manufacturing leads to changes in processes, facilities and equipment, these factors need to be considered within the virus filter design space. It may be reassuring to know that an already established technology, one that has been used to ensure the safety of biologic products for years, can be tailored to fit into and function within a continuous downstream process.

In this session, attendees will learn about the feasibility of small-scale long-term virus filtration. The studies presented will show the impact of extended process times and dynamic product streams present in continuous manufacturing on Planova 20N and BioEX filters. Proof-of-concept long-term PP7-spiked filtrations, performed for up to 4 days, showed that both virus filter types were capable of effectively removing bacteriophage PP7 (>4 log). Additionally, a mock chromatography step elution peak having increased protein, salt and bacteriophage concentrations was successfully processed on both virus filter types. Finally, MVM-spiked continuous virus filtrations were successfully imlemeted for up to 6 days at low flux. The impacts of low flux and process pauses were evaluated under these conditions.

The work presented demonstrates that small-scale viral clearance studies can be designed to model a continuous VF step with specific process parameters. The integration of continuous VF into continuous biomanufacturing processes is therefore applicable and adaptable, although it remains largely process-dependent. The ability to implement continuous VF as part of “facilities of the future” can help companies reduce footprint while achieving desired product throughputs.

Speaker:

Julie Kozaili
Scientist
Asahi Kasei Bioprocess America

This session will cover the fundamental principles behind the use of analytical ultracentrifugation to characterize AAV empty/full ratios. There will also be a discussion of experimental considerations and scope. The session concludes with a case study.

Speaker:

Akash Bhattacharya, PhD
Senior Application Engineer
Beckman Coulter Life Sciences

Adeno-associated viruses (AAVs) are the leading delivery vehicle for gene therapies due to their high efficiency of transduction and high levels of gene expression. To ensure consistency in efficacy and safety regulatory agencies require extensive characterisation and impurity analysis of the final product. This presentation focuses on protein impurity analysis of the icosahedral proteic (viral protein) shell of the AAV which contains the viral genome, optimising a method that combines CE-SDS, considered the gold standard for the characterization of therapeutic proteins, with Laser Induced Fluorescence. Our expert will describe how the method is optimized for AAV2 evaluating reproductivity, specificity and sensitivity of results.

Speaker:

Emily Walker
Senior Analyst
Intertek Pharmaceutical Services

An overview of the BioSMB multi-column chromatography technology where we discover the key concepts that make BioSMB technology the future for intensified processing. With significant enhancements in productivity and resin usage coupled with a flexible and modular column design, the customers can integrate BioSMB as the capture step into a traditional fed-batch downstream process with significant benefits over the conventional single column batch chromatography. Equivalent flow path architecture from the PD to the fully single-use Process-scale equipment allows for seamless scale-up to clinical or commercial manufacturing. Recent advances in data analytics include software that streamlines data analysis and allows for rapid analysis of large data sets. Cycle-to-cycle and column-specific data overlay enable multivariate data analysis, enabling dynamic monitoring and resin life cycle characteristics and resulting in more robust process control.

Speaker:

Jason Forte, Ph.D.
Product Specialist, Process Intensification
Sartorius North America

In recent years, significant investments have been made in upstream technologies and processes in monoclonal antibody manufacturing, with the goal of increasing upstream yields, including efforts to improve raw material characterisation, add single-use systems, perfusion systems and more precisely controlled bioreactors. On the downstream side, improvements in throughput have not kept similar pace to those for upstream, leading to potential bottlenecks in the end-to-end process. Finding efficiencies across downstream processing steps and cost-effectively aligning the productivity of downstream production with upstream yields requires complex analysis and optimization. This presentation elaborates on some key aspects of downstream processing, looking specifically at two major areas where significant improvements can be made by applying novel strategies and technologies:

• The downstream purification process, where we will demonstrate how to significantly enhance throughput while removing critical impurities. Case studies of downstream process will be presented where new generation of Protein A resin and ion exchange resins with high selectivity are utilized.
• Buffers are one of the largest constituents by volume among the hundreds of raw materials used in biologic manufacturing. We will discuss how high DBC (dynamic binding capacity) protein A resins can be used alongside with alternative methods of buffer management like single-use powder packaging, ready-to-use buffer solutions or inline dilution to help reduce facility footprint, labor hours and overall cost-of-goods.

Speakers:

Jungmin Oh
Manager, New Product Development
Avantor

Pranav Vengsarkar
Manager, Process Development
Avantor

11am EST / 4pm BST / 5pm CEST

Case studies and Process Concepts for Continuous Chromatography

(20 minute presentation followed by 10 minutes of Q&A)

Twin-column chromatography combines the power of countercurrent chromatography with the most simple multicolumn setup of two columns. Twin-column chromatography is applicable in both capture and polishing steps in downstream processing, improving throughput, saving resin and buffer, and improving yield. In this presentation the concepts of twin-column countercurrent chromatography for Capture and Polishing applications are discussed and recent case studies are presented showing the scalability of the technology.

Speakers:

Thomas Müller-Späth, Ph.D.
Director, R&D Life Science Systems
ChromaCon AG, Switzerland

11:30am EST / 4:30pm BST / 5:30pm CEST

Metadata Analysis to Improve Efficiency and Performance of Downstream Processes

(20 minute presentation followed by 10 minutes of Q&A)

• How metadata analysis can increase development efficiency and duration
• Key insights learned from analysis and how they were applied

Speakers:

Leslie Wolfe, Ph.D.
Director, Downstream Process Development
KBI Biopharma