Adeno-associated viruses (AAVs) are vital for gene therapy, but large-scale production of high-quality vectors at a high yield remains challenging. Inefficiencies in DNA packaging often result in high proportions of capsids that are either empty or contain unwanted DNA fragments. Increasing the percentage of full capsids is essential for improving the efficacy of AAV-based therapies. Conventional analytical methods struggle to monitor the ratio of full to empty capsids during upstream processing due to sample complexity.

Supported by Innovate UK, Refeyn, Rentschler Biopharma and the Cell and Gene Therapy Catapult (CGT Catapult) have collaborated to develop and apply innovative process analytical technologies (PAT) to enhance the process and efficiency of AAV manufacture. In this webinar, we will discuss the latest developments of this collaboration and how advanced analytical technologies such as mass photometry help facilitate process optimization and enhance the quality of AAV products, ultimately contributing to more effective gene therapies.

Key learning outcomes:

• Insights into the development of a high-throughput, small-scale purification method for upstream processing with small sample requirements
• How mass photometry enables precise, in-process monitoring of capsid formation and helps improve the overall quality and efficiency of AAV production

Speakers:

Nathan Sweeney
Director, ATMP Technical Strategy
Rentschler Biopharma

Amna Anwar
Associate Senior Scientist, Cell and Gene Therapy Catapult

Methods such as ELISA and HPLC represent the current industry standard for quantification of titers. The information provided by these methods is crucial not only in ensuring that an ongoing process is proceeding according to expectations, but also in aiding downstream scientists in preparing for the important step of purifying the material. However, these processes can be work and time intensive, leading to delays or variation in results. RedShiftBio's HaLCon technology provides the chance to address these issues and take the next step in titer quantification technology. Join us for an informative session that compares traditional and novel in order to determine whether this promising technology is the right step forward.

Speakers:

Matthew Sousa
Research Associate, Boston Institute of Biotechnology
RedShift

Mammalian cell platforms offer many advantages for viral vector and recombinant protein production.

NRC (National Research Council) HEK293 cells (293SF-3F6 cells) adapted to grow in suspension culture and in serum-free medium can be expanded for large-scale production of bioproducts. Generating stable producer cell lines is a key requirement; however, cloning HEK 293SF-3F6 cells using standard methods, like limiting dilution in multi-well plates and cell sorting, can cause low cell survival rates, particularly during the cloning steps.

The CellCelector Flex platform with Nanowell technology for high-throughput single-cell cloning delivers high cloning survival rates and provides complete documentation of monoclonality. It is a simpler and time-efficient approach for generating stable producer cell lines.

In this webinar, we will demonstrate how the CellCelector platform can accelerate the development of high-producing HEK 293SF-3F6 lentivirus packaging cell lines. We will also present experimental data on monoclonality of the clones isolated by this method.

Speakers:

Sophie Broussau
Cell Line Development Specialist
NRC-Montreal Canada

Viral titer testing is a critical step in cell line development, ensuring accurate quantification of viral particles for optimal production of viral vectors and vaccines. However, matrix interference is a significant challenge that often leads to inaccurate quantification of viral particles. Biological samples, such as serum or cell culture media, contain complex components that can interact with assay reagents, affecting both sensitivity and specificity.

This case study describes the development of a reliable and robust AAV capsid quantitation assay for media testing to identify the optimal cell culture media for achieving high AAV titers. The study compares traditional methods such as ELISA with advanced automated immunoassay platforms, focusing on key factors such as sensitivity, precision, throughput, and management of matrix interference.

Speakers:

Maria Germana Sanna
Field Application Scientist
Mesa Labs - Gyros Protein Technologies

Shan Gao
Sr. Scientist
Fujifilm

This presentation acts as a toolkit to manage the many stakeholders along the road to full implementation of the process or product you wish to advance. Using five real-world case studies from the field of vaccines manufacturing, with considerations based on industry guidelines, technical expertise, and advancements in digitalization, this overview of process change implementation will highlight which skills should be part of your own validation toolbox and will hopefully help accelerate and simplify the road to process change implementation in a straightforward manner.

Speaker:

Eric Doerr
Senior Project Lead for Upstream and Downstream Processing
Sanofi

Viral vectors continue to be critical in the development of new gene and cell therapies. However, in-depth characterization of these complex systems remains a challenge throughout the development and manufacturing process. Developing robust analytical methodologies to characterize multiple critical quality attributes (CQAs) for large heterogeneous viral vector systems can be challenging. In this webinar, we will discuss how to implement high throughput dynamic light scattering (DLS) and electrophoretic lights scattering (ELS) workflows initial screening, along with and multi-angle light scattering combined with size exclusion chromatography (SEC-MALS) or field-flow fractionation (FFF-MALS) for in-depth simultaneous multiple CQA characterization of AAV, LV, and other gene delivery vectors. Additionally, we will explore how to implement light scattering into bioprocess unit operations for real-time CQA analysis. The CQAs for these techniques include size, size distribution, aggregation, concentration, stability, and capsid content.

Key learning objectives:

• How DLS/ELS rapidly characterizes size distribution, aggregation, particle concentration, and stability in a high-throughput workflow.
• How SEC/FFF-MALS characterized heterogeneous samples for high resolution size distribution, payload, titer, and aggregation.
• How real time MALS characterizes and quantifies viral vectors (e.g. AAV, LV) for titer, payload, stability, and purity during TFF, AEX, and other bioprocess unit operations.

Speaker:

Dr. Parker Lee
Field Application Scientist II, Waters
Wyatt Technology

Discover how integrating Digital Tech Transfer into an MES strategy can streamline manufacturing processes, ensure data integrity, and enhance compliance with bioprocessing. Learn how to facilitate seamless process optimization across sites and accelerate the scale-up of new therapies. Don’t miss out on insights into improving efficiency and speeding up time-to-market through digital transformation.

Speaker:

Tim Adkins
Director, Digital Life Science – Operations
Zaether

In today's regulated bioprocessing environments, maintaining data integrity is critical for maintaining confidence in the development and manufacture of your therapeutic.

Data integrity is vital for reliable lab operations, ensuring all data is accurate, complete, and consistent. Laboratories often struggle with maintaining data integrity due to complex workflows and potential human error, leading to compliance failures and compromised product quality.

This webinar will explore the principles of data integrity compliance, presenting best practices and technological solutions, such as the OsmoTECH® XT Single-Sample Micro-Osmometer, to help laboratories overcome these challenges and ensure reliable results, while meeting regulatory requirements.

Key Takeaways:

• Understanding Data Integrity: Learn the fundamental principles of data integrity, its importance in laboratory settings, and common pitfalls that can compromise data quality.
• Technological Solutions: Discover how the OsmoTECH® XT Single-Sample Micro-Osmometer can enhance data accuracy and reliability, supporting laboratories in achieving data integrity and GMP compliance.
• Best Practices for Compliance: Gain practical insights into implementing best practices for maintaining data integrity, ensuring your workflow meets regulatory standards and avoids compliance issues.

Speakers:

Shweta Nair
Senior Product Manager, Biopharma
Advanced Instruments

Key Takeaways:

• New drug delivery systems for ATMPs
• How to Scale up and improve robustness of LNP process
• How to overcome the challenges in exosome production processes and characterization
• How to achieve high-titer and stable transduction for lentiviral vectors

Speaker:

Min Zhu Ph.D.
Senior VP, CDMO Operations
Innoforce

Cell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre-transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones.

Speaker:

Falguni J Patel
Principal Research Scientist
Abbvie

Stephanie E. Rieder
Senior Principal Scientist
Abbvie