Specialized Workshop F2 - Friday May 10, 2024: 7am to 5:30pm - Discussion Topic List

"Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy and Vaccine"

IMMUNOGENICITY: Latest Case Studies on Immunogenicity Risk Assessment & Mitigation for Gene/Cell/Vaccine Therapies based on Lessons Learned from Regulatory Expectations; Progress in Development of Allogenic Cell Therapy Immunogenicity Assays and Characterization of Next Generation CAR-T; Recent Regulatory Guidelines for Vaccines and impact on Bioanalysis. TECHNOLOGIES: Latest Progress in PCR-based Assays, Method Development and Validation for Genetic Multiplexing, Transgene and Target Gene Expression; Action Plan to address qPCR/bDNA Cross-Validation/Discrepancies; Increasing Applications of NGS/Genomic Assays in Bioanalysis and Developing Next Level Recommendations; Novel Applications of NGS/Genomic Assays in CRISPR Gene Editing and FFPE Sample Analysis; Industry/Regulators Focused and Interactive Discussions on Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, and Vaccine and Recent Controversial Issues

Session 1: Current Thanking on Immunogenicity Risk Assessment & Mitigation for Gene, Cell and Vaccine Therapies

  • Topic 1:

    Importance of Immunogenicity Risk Assessment & Mitigation for Gene Therapy (GT) and mRNA-Lipid Nanoparticle (mRNA-LNP): Understanding the potential immune responses triggered and their impact on safety and efficacy, methods using in vitro tools, assays for measuring immune cell activation & cytokine profiling, use of immunomodulatory agents, managing immunogenicity in clinical trials and real-world settings
    Dr. Swati Gupta, Executive Director, Clinical Immunogenicity, AbbVie

  • Topic 2:

    Are Risk-Based Approaches for Immunogenicity Assessment Relevant for Gene, Cell, and Vaccine Therapies as they are for Biotherapeutics? Understanding the drug design & clinical development strategies to differentiate Vaccine Wanted immunogenicity vs Gene & Cell Therapies Unwanted one, technical challenges & alternative approaches for high-risk products, exhaustive interpretation of clinical data
    Dr. Yuanxin Xu, Senior VP, Intellia

  • Topic 3:

    How Immunogenicity Risk Assessments for GT can be used to rate the Risk for Potential Untoward Immune Activation: Current risk assessment paradigm that may not apply to GT ( three-tiered assays, CT calculations, need for NAb assays) challenging the thinking on applying the current immunogenicity testing paradigm to GT vs customizing current practices to address unique risks for GT vs immune-related risk specific for GT
    Dr. Christine Grimaldi, Director, Assay Development Group, Regeneron

Session 2: Cell Therapy & Vaccine Immunogenicity Assays: Lesson Learned and Recent Regulatory Guidelines

  • Topic 4:

    Lesson Learned on Immunogenicity Assessment for Cell Therapy Including Incidence and Impact on PK: Immunogenicity on-set and cellular kinetics, best way to determine impact of immunogenicity on cellular kinetics, method validation to determine if the method meets the necessary characteristics to allow the use of S/N over titer, best to present data to Regulatory Agencies to seek feedback for future study support
    Dr. Johanna Mora, Senior Director, Bioanalysis, Bristol Myers Squibb

  • Topic 5:

    New Considerations for Allogenic Cell Therapies Immunogenicity Assays: What aspects are critical for anti-Extracellular Domain (ECD) assays? What is critical to examine for CAR ECD immunogenicity assay design and specificity? What are the key aspects for Anti-HLA antibody analysis and correlation with HLA-typing? Challenges with generation of Critical Reagents for the individual/armoring components?
    Dr. Christopher Beaver, Senior Director, Cell Therapies Immunogenicity and Immunoassays, Takeda

  • Topic 6:

    Interpretation of the 2023 EU EMA Guideline on Clinical Evaluation of Vaccines and its requirement for a Fully Validated Method used in pivotal trials to measure Immune Parameters as primary and/or major secondary endpoints, What does it mean to perform a Full Validation vs Fit for Purpose (FFP) Validation for Vaccine Clinical Assays? FFP Validation can be very limited or very extensive based on assay intended use when considering a specific study objective
    Mr. Francis Dessy, Clinical Assay Senior Advisor, GlaxoSmithKline

Session 3: NGS/Genomic Assays in a Regulated Environment: Cell Therapy, CRISPR Gene Editing and FFPE Sample Analysis

  • Topic 7:

    Expanded Applications of Next-Generation Sequencing (NGS) in a Regulated Environment: A new paradigm for Regulatory Agencies to consider, need for high depth sequencing of both patient somatic and germline mutations is required with high quality, need for regulatory frameworks, focus on the up front sequencing that is required as part of Individualized Neoantigen Therapy (INT) sequencing on a per patient level
    Dr. Jean-Claude Marshall, Vice President & Head of Clinical Assays, Supply and Logistics, Moderna

  • Topic 8:

    Current NGS/Genomic Analytical Tools to Enable Cell Therapy and in vivo CRISPR Clinical Studies: Integrative genomics approach combining biochemical, cell-based, and computational methods to support CRISPR Gene Editing Therapies, incorporating genomic diversity in sgRNA sequence selection to ensure efficacy and specificity across the patient population,characterization of in vivo Gene Editing Therapies
    Ms. Jessica Seitzer, Vice President Genomic Operations, Intellia

  • Topic 9:

    Development, Optimization and Validation of Automated NGS/Genomic Assays for Clinical FFPE Sample Analysis: Leveraging novel approaches to monitor clinical-grade genomic assay quality, evaluation of emerging genomics technologies to integrate within the framework of a clinical genomic lab, exploratory genomics for developing biomarkers, risks of shifting from an exploratory genomics platform to a Regulated/IVD platform
    Dr. Mark Stern, Senior Director, Clinical Genomics & Molecular Assay Development, Bristol Myers Squibb

  • Topic 10:

    Current Best Practices for Method Development/Validation of Next-Generation Sequencing (NGS): Guidance for Fit-for-Purpose Validation, software pipeline for genetic alteration calls, important factors to consider in developing NGS technologies in support of Gene, Cell and Vaccine Therapies, NGS applications for discovery vs clinical monitoring, gene editing risk assessment, similarities/difference between NGS & NanoString Validation
    Dr. Nathan Riccitelli, Associate Director, Molecular Assays, Navigate

Session 4: PCR Sophisticated Applications for Diagnostic, Dengue Detection and mRNA Quantification

  • Topic 11:

    Development of a 2-tiered Approach where PCR Sensitivity is coupled with Sequencing for Optimal Diagnostic Accuracy: Amplicon sequencing used to increase specificity when used with orthogonal diagnostic approaches, use of very specific primers in validation by leveraging both contrived and real samples for derivation of specificity, sensitivity, and LOD, assay intended use where specific targets are validated
    Dr. Warren Kalina, Executive Director Diagnostic Assays, Pfizer

  • Topic 12:

    Challenges in the Development of Quantitative Dengue Detection PCR: Thorough understanding the PCR process and key steps involved in the multiplex process, common issues that arise during qPCR method development, focus on how a change in reagent lot can impact qPCR assay and affect the sensitivity, troubleshooting PCR issues in Dengue detection, highlighting the importance of careful experimentation
    Dr. Dewal Jani, Director, Clinical Assay Development, Vaccine Research and Analytics, Takeda

  • Topic 13:

    Advantages of Using qPCR rather than bDNA for mRNA-Derived Protein Quantification to support PK evaluation: Comparison of data and performance, strategy for conversion from bDNA to quantitation by qPCR, challenges associated with choosing an appropriate reference standard for quantitation of mRNA, bioanalytical support for mRNA therapeutic including selection of endpoints and lifecycle management of assays
    Mr. Jason DelCarpini, Director, Bioanalytics, Moderna

Session 5: 2024 White Paper in Bioanalysis

  • 2024 White Paper on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy and Vaccine

    Consensus & Conclusions on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy and Vaccine for 2024 White Paper

Session Finale: ASK THE REGULATORS! Interactive Panel Discussion with All the Regulators

  • Regulatory Feedbacks on Submitted Studies and Inspection/Audit Outcomes on Gene Therapy, Cell Therapy & Vaccines

    Regulatory Panelists:

    • Dr. Zuben Sauna (US FDA CBER)
    • Dr. Vijaya Simhadri (US FDA CBER)
    • Ms. Leslie Wagner (US FDA CBER)
    • Dr. Joshua Xu (US FDA NCTR)
    • Dr. Alessandra Buoninfante (EU EMA)
    • Mr. Christian Mayer (Austria AGES / EU EMA)
    • Dr. Shirley Hopper (UK MHRA)
    • Dr. Meenu Wadhwa (UK MHRA)
    • Dr. Sandra Diebold (UK MHRA)
    • Dr. Sandra Prior (UK MHRA)
    • Dr. Omar Tounekti (Health Canada)
    • Dr. Sarah Wassmer (Health Canada)
    • Dr. Chad Irwin (Health Canada)
    • Dr. Julie Joseph (Health Canada)
    • Dr. Yoshiro Saito (Japan MHLW)




Agenda at a Glance Agenda at a Glance