8:00 am Check-In & Coffee
8:55 am Chair’s Opening Remarks
9:00 am The Road to Approval: Gene Therapy Analytical Package From Early IND to Approval
Synopsis
- Lean release analytical package for the initiation of Phase 1/2 clinical trials: minimum requirements and common challenges
- Evolution of the analytical package through different stages until filing for marketing approval: extended vs characterization vs release
- Regulatory expectations at the time, of BLA/MAA approval: first hand, learnings from parallel filing in the US, and EU
OPTIMIZING YOUR ANALYTICAL STRATEGY TO MEET REGULATORY REQUIREMENTS
9:30 am The Critical Role of First-Principles, Fundamental Techniques in Gene Therapy
Synopsis
- Current methods used to characterize AAV [empty/partial/full] are compared and contrasted along with several case studies highlighting the utility of first-principle, fundamental techniques such as UV-Vis, Light Scattering, and SV-AUC in gene therapy characterization
- These methods are useful for deconvoluting interpretation errors caused by the ‘Jingle’ fallacies common in gene therapy analytics – e.g., the difference between mass and number weightings when considering constructs such as “%empty” and “%HMW”
- While it’s tempting to neglect these fundamental methods once more routine methods such as PCR are online, these methods are at higher risk for method-induced artifacts
10:00 am Speaking Slot Reserved for Bio-Rad
10:30 am Morning Refreshment Break & Speed Networking
Synopsis
As the gene therapy analytical development community is reunited, this valuable session will ensure you can connect with your peers in the room to make new and lasting connections. Also, don’t forget to enjoy some refreshments before we split off into the three different tracks: bioassays & molecular biology, physicochemical properties and process development & CMC.
BIOASSAYS
Developing Phase-Appropriate Functional Potency Assays
11:30 am Evolution of a Product Specific Potency Bioassay for an AAV2-Based Gene Therapy
Synopsis
- Addressing common considerations involved in developing a potency assay
- Presenting an example functional potency assay approach
- Validating a potency assay by establishing linearity, accuracy, specificity, stability, and robustness
12:00 pm Developing Robust Bridging Techniques to Aid Advancement from Early to Late-Stage Potency Assay Development
Synopsis
- Advancing from early-stage to late-stage potency assay development
- Demonstrating comparability between analytical methods
- How to ensure methods are suitable for late-phase gene therapy product
12:30 pm Speaking Slot Reserved for Intertek
PHYSICOCHEMICAL PROPERTIES
Applying Different Tools for Capsid Characterization & Aggregation
11:30 am Exploring the Emerging Trend of CDMS as a Novel Tool for Rigorous Genome Assessment & Effective Partial Capsid Characterization
Synopsis
- Introducing CDMS as an emerging tool to characterize intact capsid mass without the need for disruptive denaturation
- Understanding the use of CDMS readouts for heterogeneous capsid characterization, genome mapping, and refined partial particle characterization
- Presenting and contrasting data from different CDMS machines
- Incorporating CDMS into your analytical strategy to prove increased resolution over AUC and traditional tools
12:00 pm PANEL: Comparing Traditional Methods for Aggregation Analysis & Effective Safety Profiling
Synopsis
- Comparing DLS, vs Size Exclusion Chromatography vs Asymmetrical Flow Field-Flow Fractionation to determine orthologous methods that can be used to increase the accuracy of profiling aggregates
- Using aggregation analytical tools to determine whether empty or full capsids more prone to aggregation
- Discussing the regulatory expectations on aggregation to inform what areas of aggregation formation should have mitigation strategies imposed
12:30 pm Speaking Slot Reserved for Nanomosaic
PROCESS DEVELOPMENT & CMC
Advancements in Quality Control & Product Characterization
11:30 am CASE STUDY: Inside & Outside Characterization of HostCell Impurities to Determine the Relative Impact of Process & Product-Related Impurities
Synopsis
- Qualifying analytical methods with consideration of insideoutside impurities
- Strategy and insight, into qualification for methods in determining impurities
- Discussing regulatory expectations on impurity method qualification and alternative protocols
12:00 pm Unraveling the Complexity of the AAV Packaging Process During Cell Culture: Insights from Deep Characterization & Molecular Understanding
Synopsis
- Delving into the complexity of the AAV packaging process at the molecular level, uncovering key insights into its mechanisms and dynamics
- Learn how deep characterization techniques are being utilized to generate robust datasets, providing valuable insights into process optimization and standardization
- Exploring the implications of molecular understanding in addressing challenges such as consistency, scalability, and standardization, and discovering innovative approaches to enhance AAV gene therapy manufacturing
12:30 pm Optimizing Viral Vector Platforms for Enhanced Gene Therapy Efficacy
1:00 pm Lunch & Networking
MOLECULAR BIOLOGY
Assessing New Approaches for Genome Integrity Analysis
2:00 pm Optimizing a Multiplexed ddPCR Assay for Viral Titer Quantification & Characterization of AAV Vector Genome Integrity
Synopsis
- Developing a successful multiplexing ddPCR Assay for genome integrity analysis
- Optimizing ddPCR methods to provide a more accurate assessment of rAAV vector genome integrity
- Presenting data linking sample preparation procedures, such as pipetting and heating, to genome fragmentation to optimize ddPCR protocols and align readouts to orthogonal approaches
2:30 pm ROUNDTABLE: Comparing qPCR vs dPCR vs ddPCR Approaches for Assessing Genome Integrity
Synopsis
- Comparing the strategies to deal with a mismatch in titer results – which results are accurate?
- Explaining regulatory feedback on the most appropriate methods and attitudes to transitioning to digital PCR
- How can PCR approaches be used orthogonally with CDMS & AUC for effective characterization of partial particles?
3:00 pm Speaking Slot Reserved for Progen
PHYSICOCHEMICAL PROPERTIES
Deep Dive into AAV Characterization & Improving Assay Resolution
2:00 pm Rapid High-Resolution Size Distribution Protocol for Improving the Characterization of Adeno-Associated Virus Using High Speed SV-AUC (Hs-SV-AUC)
Synopsis
- Discover the advantages and challenges of doing hs-SV-AUC and how those challenges have been successfully overcome
- Exploring what new information we are beginning to see in applying this protocol to real AAV samples
- Taking a deeper look at what is real vs what may not be real when modeling SV-AUC data to extract size-distribution information
- Discussing the challenges of using an instrument (the analytical ultracentrifuge) where there is only one manufacturer
2:30 pm PANEL: Using Orthogonal Approaches to Increase Assay Resolution & Accurately Quantify Empty-Full Ratios
Synopsis
- Understanding how to correlate orthologous methods, such as NGS, to qualify AUC and determine genome content
- Validating ratios by identifying trends appearing from using orthogonal methods in the absence of adequate reference standard materials
- Determining how to holistically apply empty-full characterization technology to build a fuller picture of genome integrity
3:00 pm Roundtable Discussion: Advanced Analytical Techniques for Assessing AAV Heterogeneity
Synopsis
- Evaluating the effectiveness of sedimentation velocity AUC in distinguishing between full and partial AAV capsids
- Discussing the advantages and limitations of AUC compared to other analytical methods such as TEM, DLS, and SEC-MALS
- Exploring the integration of multiple analytical techniques to achieve comprehensive characterization of AAV heterogeneity
PROCESS DEVELOPMENT & CMC
Advancing Vector Selection, Yield Optimization, & Cell Line Development
2:00 pm Host Cell Line Development: Developing & Optimizing Cell Lines for Vector Production
Synopsis
- Understanding the criteria for choosing cell lines compatible with vectors that support high production levels
- Discovering techniques to enhance cell lines’ ability to produce high titers of viral vectors
- Exploring strategies to adapt cell lines for suspension culture to improve scalability and yield
2:30 pm Roundtable: Vector Selection: Choosing the Appropriate Viral (or Non-Viral Vector) for Gene Delivery
Synopsis
- Understanding the unique properties of AAV, lentivirus, and adenovirus, including tropism, transduction efficiency, and immune response
- Exploring the benefits and challenges of plasmids, liposomes, and nanoparticles in gene delivery
- Strategies to optimize gene delivery while minimizing immunogenicity and off-target effects
3:00 pm Speaking Slot Reserved for Mirus Bio
3:30 pm Afternoon Refreshment Break & Poster Session
Synopsis
Join us for an enlightening poster session to exchange ideas and stay updated on the latest trends and innovations in gene therapy analytical development. Don’t miss this chance to engage with the experts and enhance your understanding of the dynamic field of gene therapy.
ADVANCING VIRAL VECTOR CHARACTERIZATION: INSIGHTS INTO EMPTY/FULL RATIOS FOR VIRAL VECTORS
4:30 pm Speaking Slot Reserved for Beckman Coulter
5:00 pm Benchtop TD-NMR: A New Tool for Biophysical Characterization of AAV
Synopsis
- Benchtop time domain (TD)-NMR is an agile noninvasive/nondestructive platform for AAV characterization
- Benchtop TD-NMR can provide data on AAV attributes such as empty/full ratio in minutes without the need for a dedicated NMR SME
- Benchtop TD-NMR can provide solutions for characterization of complex therapeutics not generally accessible to traditional high-field FTNMR
5:30 pm Using AUC to Reveal the Heterogeneity of AAV & Better Resolve Partial from Full Capsids
Synopsis
- Uses theoretical calculations and experimental data to assess resolving power of the sedimentation velocity AUC method for mixtures of AAVs
- Compares and contrasts the resolution of several other methods