Specialized Workshop M2 - Monday May 06, 2024: 7am to 5:30pm - Discussion Topic List

"Advanced Strategies for Biomarkers and IVD/CDx Assays"

From Discovery/Exploratory Biomarkers to Clinical/Confirmatory Biomarkers Latest Progress in LBA & Mass Spec Development/BAV; Recent Issues in Development of CDx for Patient Selection/Stratification and Drug Response Monitoring; State-of-the-art Multiplex/OMICs Discovery Biomarkers Novel Platform; Current Challenges in Implementing Clinical Biomarkers as Primary Endpoints; Recent Development/Industry Practice in Vaccine Biomarkers LBA Development/Validation; Recent Progress in Fit-for-Purpose Biomarker Assay Validation (FFP BAV) Application and ISR/Parallelism; Novel Data on Lesson Learned from using New Platforms in Real-Life Situations; Current Best Practices on Tissue Biomarkers; Industry/Regulators Focused and Interactive Discussions on BAV, IVD/CDx and Recent Controversial Issues

Session 1: Current Challenges in Biomarker Assays Development/BAV: Parallelism, Free Target Measurement, GCLP vs CLIA, New Platforms

  • Topic 1:

    Critical Role of Parallelism for LBA, Hybrid (IA-MS) and Small Molecules Mass Spec Biomarker Assays: Methods to assess whether parallelism is achieved, rigorous full curve statistical methods, reconsiderations due to lack of parallelism and impact on assay/what is measured, issues with isoforms/circulating pro-forms/binding partners, understanding when a lack of parallelism is expected, value of ISR vs Incurred Sample Parallelism
    Dr. Lindsay King, Senior Director, Biomarker Head, Clinical Bioanalytics, Translational Clinical Sciences, Pfizer

  • Topic 2:

    How to Achieve an Accurate Free Target Measurement as Target Engagement (TE) and Efficacy Biomarker: LBA kinetics over-estimation of free target, challenges with soluble drug targets present in high concentrations due to high dilution needs, specific LBA platforms for free target measurement, importance of minimal sample dilution/matrix effect/sample incubation time, risk mitigation over life cycle of an assay
    Mr. Mark Dysinger, Associate Director, Bioanalytical Development, Alexion

  • Topic 3:

    Application of Fully Automated Diagnostic Platforms for Biomarker Assay Development based on Purpose of the Assay and how the Biomarker will be used in the Clinical Trial: FFP BAV strategy, combing requirements from GCLP & Clinical Diagnostic/CLIA, strategies for Cross-Validation between Phadia & EIA and among three different sites/countries, challenges of exporting incurred samples to/from foreign countries
    Dr. Kai Wang, Scientific Director, Immunoassay Bioanalysis and Biomarker, GlaxoSmithKline

  • Topic 4:

    Practical Applications of Olink Technology in Discovery Biomarkers Development: In depth focus on bioanalytical utility of Olink targeted Inflammatory Biomarkers Assays in clinical trials, ability of this Emerging Technology to detect biomarkers which are below detection limit in traditional multi-omics studies, development of cytokine & chemokines panels reliably detected in multiplex for disease progression and/or stratification/prediction evaluation
    Mr. Jeff Chen, Associate Director, Bioanalysis & Biomarker Discovery, Astra Zeneca

Session 2: Vaccine Biomarkers LBA: Focus on Automation, Assay Maintenance/Performance Monitoring and Complex Matrices Development/Validation

  • Topic 5:

    Advantages of Full Automation in Vaccine Biomarker LBA: Enabling Single Well Analysis (singlicate), insignificant sample failure rate and high throughput sample testing, possibility to automate also emagglutination inhibition assay and cell-based neutralization assays, FFP BAV demonstrated with automated assays including assay precision, linearity, stability, superior performance vs non-automated LBA during sample testing
    Dr. Liang Zhu, Director, Immunoassay, Clinical Biomarker Laboratory, Moderna

  • Topic 6:

    Innovative Vaccine Biomarkers LBA Development/Implementation of High Throughput 384-Well Automated Platform: Efforts to transition from manual methodology to a fully automated platform, robust sample dilution program, simultaneous testing of multiple assays, evaluation of automated performance characteristics during validation and demonstrated alignment with the original LBA allowing a single 384-sample deep well to be stamped across several assays
    Dr. Rocio Murphy, Senior Director and Head of Global Clinical Immunology, Sanofi

  • Topic 7:

    Critical Importance of Maintenance and Performance Monitoring for Vaccine Biomarker LBA: Strategies for demonstrating stability over a very long period of time, main sources of variability, critical reagents, operators, equipment, change in assay design, When is a bridging strategy sufficient and when is not? How to ensure that a change will not introduce an excursion in assay performance?
    Dr. Karl Walravens, Head of Clinical Immunology, GlaxoSmithKline

Session 3: Mass Spec Assays vs LBA for Measuring Biomarkers and EU IVDR 2017/746 Impact on Global Biomarker Strategy

  • Topic 8:

    Mass Spec vs LBA for Measuring Protein Biomarkers in Tissue & Biofluids: Crucial importance for measuring Target Engagement (TE) in support of siRNA from Discovery to Clinical Development, use of Mass Spec to confirm specificity of LBA for a circulating TE biomarker for siRNA development candidate, challenges related to specificity of LBA Critical Reagents identified by discordant tissue and protein mRNA data
    Dr. Sarah Bond, Senior Director, Bioanalytical Sciences, Alnylam

  • Topic 9:

    Advanced Design for Reagent-Free nano-LC HRMS Biomarker Assay: Deep correlation between Mass Spec Assay with 2 different LBA for ACTH using clinical sample, use of Bland-Altman and ISR-like analyses, RSM inconsistency, LBA issue to discriminate between Cushing's disease and ectopic syndrome, EU IVDR 2017/746 impact on global biomarker strategy of steroid hormones, CE-marked assays in EU vs LTD Mass Spec Assays
    Dr. Barry Jones, Director, Bioanalysis & Biomarkers, Crinetics

  • Topic 10:

    An in depth understanding of the European In Vitro Diagnostic Regulation 2017/746 (IVDR) effective on May 26, 2022, replacing In Vitro Diagnostic Medical Devices Directive 98/79/EC (IVDD), EU IVDR Article 58: "any test that informs medical decisions may require prior authorization from EU Competent Authorities...prior to its use in a clinical trial." Industry/Regulators' agreement the Biomarker Assays may be subject to these additional requirements
    Mr. Brian Baker, Executive Director, IVD Regulatory Affairs, Regeneron

Session 4: Development & Fit for Purpose Validation (FFP BAV) of CDx/IVDs: Focus on CDx for AAV- based Gene Therapies (GT)

  • Topic 11:

    Biomarker Assays used to inform decisions about patient treatment as IVDs and subject to geography- specific regulations, Biomarker Assays deemed to be necessary for safe and effective use of a drug as CDx, Biomarker Scientist's need for thorough planning in Development/BAV of CDx/IVDs, coordination with key points in the drug development timeline, interaction with many key stakeholders in CDx development who should be consulted for input
    Dr. Agnes Seyda, Director, Translational Sciences & Diagnostics, Bristol Myers Squibb

  • Topic 12:

    CDx or not CDx for AAV- based Gene Therapies (GT)? What can we learn from approved GT and what we should not? When do we need to think about developing CDx? Is Clinical Laboratory Improvement Amendments (CLIA) a requirement in the context of clinical trials? What is the best CDx Platform for specific AAV serotypes in GT and what CDx assay platform to choose? Is better to use assay generating Yes/No results or Titer?
    Mr. Michele Fiscella, Vice President Translational & Bioanalytical Sciences, Regenxbio

  • Topic 13:

    Reasonings & Strategies in the Development/BAV of a AAV5 TAb Assay to assess AAV5 Seroprevalence and as CDx Assay for screening patients in Phase 3 clinical studies: Multiple assay methodologies provide different insight to pre-existing immunity, Total Antibody assays (TAb) vs Cell-Based Transduction Inhibition assays (TI), clinical/bioanalytical considerations on antibodies to AAV arise from natural exposure to serotypes and impact on transduction by AAV-based GT
    Ms. Andrea Van Tuyl, Director, Bioanalysis, BioMarin

Session 5: 2024 White Paper in Bioanalysis

  • 2024 White Paper on Advanced Strategies for Biomarkers and IVD/CDx Assays

    Consensus & Conclusions on Advanced Strategies for Biomarkers and IVD/CDx Assays 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 Biomarkers & CDx/BAV

    Regulatory Panelists:

    • Mr. Abbas Bandukwala (US FDA CDER)
    • Ms. Leslie Wagner (US FDA CBER)
    • Dr. Joshua Xu (US FDA NCTR)
    • Dr. Shirley Hopper (UK MHRA)
    • Dr. Alessandra Buoninfante (EU EMA)
    • Dr. Hilke Zander (Germany PEI / EU EMA)
    • Dr. Joerg Engelbergs (German PEI / EU EMA)
    • Dr. Chad Irwin (Health Canada)
    • Dr. Julie Joseph (Health Canada)
    • Mr. Joao Tavares Neto (Brazil ANVISA)
    • Ms. Dulcyane Neiva Mendes (Brazil ANVISA)




Agenda at a Glance Agenda at a Glance