8:50 am Chair’s Opening Remarks
EXPANDING THE ANALYTICAL TOOLBOX BEYOND AAV
9:00 am Developing Analytical Tools to Assess the Complex Payloads of an LNPbased HBV-Targeting Gene Therapy
Synopsis
- What does the analytical control strategy look like for a frontline LNP approach?
- Understanding the high-level regulatory requirements for LNP to ensure all relevant CQAs are addressed
9:30 am Establishing Analytical Techniques for RNA-based Vector Modalities to Enhance Product Development
Synopsis
- Implementing new analytical methods for the development of RNA-based vector modalities
- Identifying relevant CQAs, including for LNP-based delivery systems
- Presenting data on lot release and characterisation methods used for the clinical development of RNA products
- Addressing quality control challenges in RNA-based gene therapies through the implementation of robust analytical techniques
10:00 am (NEW DATA) (NEW TECH) Developing an Analytical Toolbox for the Efficient Characterisation of Viral & Non-Viral Particle Conjugations
Synopsis
- Presenting platform technology on a new generation of bio-conjugated vectors
- Expanding the platform of bio-conjugated vectors to include lipid nanoparticles
- Developing a relevant analytical toolbox and using orthogonal analytical methods to characterise these bio-conjugated vector modalities
10:30 am Morning Refreshments & Networking
BIOASSAYS/MOLECULAR BIOLOGY
NGS TECHNIQUES FOR EXTENDED VECTOR CHARACTERISATION
11:30 am (CASE STUDY) Using Contemporary NGS Technologies Orthogonally to Effectively Characterise AAV Capsid Content.
Synopsis
- Exploring how to use NGS in practice
- Comparing the strengths and weaknesses of different NGS techniques (PacBio vs ONT vs Illumina)
- Reporting first hand experiences with using NGS: lessons learnt, useful tips & next steps
12:00 pm (NEW DATA) Utilising NGS Methods to Measure Whole AAV Genomes & Improve Particle Characterisation
Synopsis
- Presenting long-read sequencing methodologies for precise measurement of complete AAV genomes in gene therapy vectors
- Optimising sequencing protocols to avoid fragmentation during sample preparation
- Presenting plasmid sequencing data and the analysis of transposon integration events
- Highlighting advantages of NGS in comparison to other molecular tools
PHYSICOCHEMICAL CHARACTERISATION
CONTEMPORARY CHROMATOGRAPHIC TOOLS FOR ANALYSIS OF CQAS
11:30 am Exploring the use of SEC-MALS to Establish a High-Throughput, Efficient Analytical Method to Supplement ddPCR
Synopsis
- Real-world Applications of SEC-MALS for the analysis of inprocess samples
- Benchmarking SEC-MALS against alternative tools such as ddPCR in the analytical development and QC testing of AAV vectors
- Implementing methods for validating SEC-MALS instrumentation
12:00 pm (NEW DATA) Utilising HPLC for Analysis of Aggregation & to Enhance Separation Resolution Between Empty, Full & Partial Capsids
Synopsis
- Refining HPLC to enable quantification of critical CQAs including aggregation and empty-full ratio
- Presenting data establishing robust separation resolution between full and empty particles
- Understanding mechanisms for validating contemporary HPLC techniques across AAV products
- Benchmarking HPLC to cryo-EM and ddPCR-ELISA to demonstrate reduced variability
12:30 pm Lunch & Networking
ANALYSING HOST-CELL DNA IMPURITIES TO GUIDE PROCESS DEVELOPMENT
1:30 pm Characterising & Assessing the Impact of Host-Cell DNA Impurities to Better Understand Regulatory Requirements
Synopsis
- Using PCR and next generation sequencing approaches to analyse residual host-cell DNA
- Discussing the relevance of E1A, residual plasmid and recombination-competent host-cell DNA
- Understanding regulatory perspectives on host-cell DNA quantity thresholds
2:00 pm (NEW DATA) Characterising Chimeric DNA Species to Better Understand & Guide Process Development
Synopsis
- Developing our understanding of the true genomic content of viral particles
- Understanding DNA recombination hotspots
- Utilising chimeric construct reads for sequence-based optimisation of gene therapy products
- Comparing Short vs Long read sequencing approaches
REFINING THE ANALYTICAL TOOLBOX FOR EXTENDED PHYSICOCHEMICAL CHARACTERISATION
1:30 pm (CASE STUDY) (NEW DATA) Unpicking The Relative Contribution of AAV Glycosylation to Vector Function in Order to Better Understand Interstudy Variability
Synopsis
- Introducing primary mass spectrometry data identifying AAV glycosylation status
- Assessing the impact of AAV glycosylation on VP ratios and overall vector function
- Determining VP ratios as a critical CQA during AAV vector manufacture
2:00 pm Introducing High Resolution Methods Of MassSpectrometry Based Purity Analysis to Accelerate Vector Characterisation
Synopsis
- Using mass spectrometry to efficiently and accurately characterise AAV capsids and VP ratios
- Structural characterisation of proteins and posttranslational modifications
- Linking higher order protein structure to product function to understand the relative importance of vector impurities
2:30 pm Afternoon Refreshments & Networking
IMPLEMENTING & VALIDATING ANALYTICAL TOOLS DURING UPSCALING & MANUFACTURING
3:30 pm Evaluating Best Practice for Analytical Technology Transfer Process to Ensure Smooth Transitions During Upscaling
Synopsis
- Understanding the GMP requirements during the technical transfer of analytical methods to enable effective upscaling
- Establishing robust methodologies for sharing protocols, custom reagents, and assay standards during tech transfer
- Discussing analytical methods to develop confidence in CQA preservation throughout manufacturing, storage, and shipment
4:00 pm Streamlining Manufacturing & Analytical Approaches to Facilitate Efficiency
Synopsis
- Understanding the importance of interlinking QC and robust analytics for product characterisation
- Effectively defining a robust manufacturing process to facilitate analytical efficacy