DAY TWO - Thursday July 18, 2024
8:00 am Morning Networking Coffee
8:50 am Chair’s Opening Remarks
ESTABLISHING CRITICAL UPFRONT CONSIDERATIONS FOR EFFECTIVE POTENCY ASSAY DESIGN TO STRENGTHEN REGULATORY SUBMISSIONS
9:00 am Designing Activity Assays for Non-Enzymatic/Structural Protein Products to Confidently & Robustly Measure Potency
Synopsis
- Generating a release assay for measuring downstream protein effects to supplement binding assays and prove potency
- What kind of in vitro assays are acceptable? Assessing and clarifying agency expectations on binding assay data versus gene-knockdown versus true activity assays
- Establishing alternative assays to prove that binding studies are meaningful and indicative of potency
9:30 am (NEW DATA) Designing a Potency Assay for a Product with a Complex or Unknown Mechanism of Action to Mimic In Vivo Function & Satisfy Regulators
Synopsis
- Brainstorming approaches for developing a functional potency assay for proteins with a complicated or unknown function in vivo
- How many protein read-outs are necessary for products undergoing posttranslational modifications or other structural changes?
- Determining the stage of development from which multiple protein assays are required to anticipate and overcome the regulatory challenge
10:00 am (NEW DATA) Develop MoA-Based Potency Assay for a Highly Glycosylated Structure Protein
Synopsis
- Developing a quantitative and high throughput functional potency assay for a highly glycosylated structure protein
- Overcoming limitations associated with vectors with muscle-specific promoter
- Enhancing assay signal windows to facilitate assay development
10:30 am ROUNDTABLE: Discussing the Influence of Post-Translation Modifications & Other Manufacturing Considerations on Gene Therapy Vector Potency to Better Define Relevant CQAs
Synopsis
Roundtable discussions include a larger focus on group discussion. A moderator will introduce the session topic and attendees then split into groups to discuss a series of predetermined agenda points. At the end, all groups report back on their discussions, and findings are collated.
This roundtable will cover:
- Balancing quality with quantity of reference standards – How do you ensure sufficient quantity of viral vectors for clinical supply?
- Selecting appropriate cell lines in the generation of reference materials
- Establishing protocols for dealing with small batches of reference standards and low sample numbers
11:00 am Morning Refreshments & Networking
MINIMIZING VARIABILITY & INCREASING SENSITIVTY TO ENHANCE CELL-BASED POTENCY ASSAYS
11:30 am (CASE STUDY) (NEW DATA) Controlling Variability in Potency Methods for Hepatic Indications
Synopsis
- Classifying the potential sources of variability in cell-based assays
- Discussing the implementation of semi-automation as a mechanism to reduce sources of variability
- Establishing assay and sample acceptance criteria to monitor the method performance
12:00 pm Session Reserved For Curibio
12:20 pm Enhancing Cell-Based Potency Assay Sensitivity to Overcome Limited Viral Vector Quantity
Synopsis
- Enhance the transduction efficiency to improve transgene expression
- Evaluate the impact of full/partial/empty vector on potency
- Using potency assays to facilitate the process development optimization
12:50 pm ROUNDTABLE: Selecting Appropriate Cell Lines During Potency Assay Development to Maintain Biological Relevance & Reflect Potency In Vivo
Synopsis
Roundtable discussions include a larger focus on group discussion. A moderator will introduce the session topic and attendees then split into groups to discuss a series of predetermined agenda points. At the end, all groups report back on their discussions, and findings are collated.
This roundtable will cover:
- Discussing the factors influencing the appropriate selection of transducible cell lines for batch testing
- Comparing the relative advantages and disadvantages of working with immortalized versus primary cell lines for potency testing
- Overcoming limitations associated with utilizing vectors with high specificities in their tropism
- Understanding the importance of measuring transduction efficiency on your selected cell line to determine biological relevance
1:20 pm Networking Lunch
IMPLEMENTING EMERGING TECHNOLOGIES INTO POTENCY ASSAY APPROACHES
2:00 pm (CASE STUDY) (NEW DATA) A Potency Assay Development Process – Comparing Analytical Tools to Determine HPLC as the Preferred Readout Method
Synopsis
- Comparing HPLC with various other options such as luciferase reporter, enzyme activity, and LC-MS assays
- Levering HPLC to define a robust MOA potency assay strategy suitable for commercialization
- How does an HPLC approach align with the new FDA potency guidance?
2:30 pm PANEL DISCUSSION: HPLC & Mass Spectrometry-Based Approaches: Are they Worth Integrating into Your Overall Potency Strategy?
Synopsis
- Weighing up the relative advantages and disadvantages of using mass spectrometry and HPLC tools to assess potency and inform assay suitability
- Evaluation the impact of these technologies on reducing variability, managing time-consuming readouts, and ensuring sample stability
- Where do current methods face limitations in their capacity to detect functional activity alterations?
- Highlighting the need for coordination between bioassay and analytical teams to optimize assay throughput using these novel tools
3:00 pm Afternoon Networking Break
DESIGNING POTENCY ASSAYS FOR NOVEL GENE THERAPY MODALITIES
4:00 pm Outlining the Key Considerations for Developing Potency Assays for Arenavirus-Based Gene Therapy Products Meet Regulatory Demands
Synopsis
- Outlining the emergence of gene therapy modalities beyond traditional AAV approaches
- Evaluation of appropriate potency assays to reflect the Mode of action of arenaviral therapeutics
- Why T cells matter – challenges in the development of CD8+ T cell activation assays
4:30 pm Potency strategy considerations for LNPs containing multiple active ingredients
Synopsis
- Discussing the requirements of measuring potency for gene therapy products with multiple active ingredients
- Establishing a phase-appropriate approach reflective of the presumed mechanism of action of both drug substance(s) and drug product to maximize product understanding
- Developing an LNP potency matrix linking characterization to product release assays
5:00 pm Developing a Potency Assays Strategy for a Novel Human Bocavirusbased Gene Therapy
Synopsis
- What is human bocavirus and why is it is suitable vector for gene therapies against Cystic Fibrosis?
- Utilising an Ussing chamber chloride ion current as a novel functional assay to assess potency
- Reflecting on the lessons and learnings from using a novel vector approach to overcome developmental hurdles upfront