Specialized Workshop Th1 - Thursday May 09, 2024: 7am to 5:30pm - Discussion Topic List

"Advanced Strategies for Ligand-Binding Assays"

LBA Applications in Novel Modalities; Leveraging Multiple Platforms in Integrative Bioanalysis; Solving New & Old Challenges with LBA Innovative Approaches in Complex Biotherapeutics, PK/Biomarkers/ADA LBA; TAb/NAb for Gene Therapy Method Development/Validation; Super Sensitive Technology Advancements in ADA LBA Development; Latest Progress in Critical Reagents & Positive Controls Generation/Performance; Novel Approaches for Bridging Highly Variable Critical Reagents Lots; Critical Reagent for New Modalities and New Assays Platforms; Application of Discovery Bioanalysis Solution in Regulated Bioanalysis

Session 1: LBA in Gene Therapy: Innovative Approaches in LBA for Total Antibody/Neutralizing Antibody (TAb/NAb) Assays Supporting GT Trials

  • Topic 1:

    Innovative Use of Alkaline Buffer in LBA to Improve Drug Tolerance: For AAV GT target lysosomal storage, failure of commonly used Acid Dissociation sample pre-treatment to solve Interferences, high levels of persistent anti-drug antibodies to the Enzyme Replacement Therapy (ERT), monitor relative TAb & NAb to assess the Tolerance Induction or Treatment-Boosted ADA production supporting GT clinical trials
    Ms. Liching Cao, Senior Director Bioanalytical Operations, Sangamo

  • Topic 2:

    Unique Challenges of Developing/Validating Bioanalytical LBA for Transgene Protein following GT administration: Transgene protein functional activity detection, considerations in non-clinical vs clinical assays developments, understanding current Regulatory Guidelines and limitations of using those in the GT space, potential gaps in available Regulatory Guidelines and how could be filled in the future
    Dr. Andria Culbert, Associate Director, Regulated Bioanalysis, Spark

  • Topic 3:

    Development of novel Immune Complex (IC) Assay to detect total anti-AAV2 antibodies (TAb) in GT: Comparison between IC Assay lower capsid material consumption & sensitivity vs drug tolerant LBA able to detect both free/bound anti-AAV2 antibodies, use of non-spiked samples as a Negative Control (NC) since the IC assay detects immune complexes, specificity control for discrimination between anti-AAV2 positive/negative samples
    Dr. Kay-Gunnar Stubenrauch, Lead Genomic Medicine, Bioanalytics and Biomarkers, Roche

  • Topic 4:

    Specific/Unique Challenges in LBA Development/Validation for Expressed Enzyme Gene Therapy: Impact on enzyme stability/conformation due to buffer/matrix components, pH, platform selection, issues in altering Enzyme ability to metabolize substrate and/or binding kinetics of capture/detection reagents, lack of true RSM, use of surrogate for the expressed transgene enzyme, difficult development of enzyme NAb assays
    Dr. Richard Hughes, Scientific Director, Immunoassay, Resolian

Session 2: LBA in Immunogenicity: Super Sensitive ADA/NAb LBA, Strategies on ADA LBA Formats and Singlicate Validation

  • Topic 5:

    Super Sensitive ADA LBA? When are they needed and help? When do they hurt? Application of New and Improved Super Sensitive NAb Assay Formats with Sensitivity Equivalent to ADA Assays: Recent advancement in LBA using ACE, SPEAD and BEAD formats, clinical impact of NAb detected by ACE-NAb approach, when to use super sensitivity and drug-tolerant NAb assays and challenges that these assays have not overcome yet, points to consider for the future, evolution and/or application of NAb assays
    Dr. Shalini Gupta, Senior Director, Translational Safety & Bioanalytical Sciences, Amgen

  • Topic 6:

    Up-to-date Strategies on ADA LBA Formats and its Critical Impact for the Results of the Samples Measurement: Advantages of homogeneous Bridging Assay formats, capture/detection reagents combined with sample matrix simultaneously, elimination of wash-step to detect low-affinity or rapid off-rates antibodies, using of heterogenous assays for separation of immunocomplexes with improved specificity
    Dr. Rita Martello, Scientific Director, EMD Serono

  • Topic 7:

    Recent Developments in ADA LBA Validation Strategy with Upfront Duplicate vs Singlicate Comparison of Precision: Current ICH M10 BMV Guideline allows Single-Well Analysis (singlicate) for PK LBA stating that "study samples can be analyzed using an assay format of 1 or more wells per samples", What about ADA LBA? Evaluation of clinical applications of PK & ADA LBA singlicate approach for a tri-specific antibody
    Ms. Susana Liu, Associate Director, Biologics Clinical Assay Lead, Pfizer

Session 3: LBA Critical Reagents: Enhanced Approaches for Characterization of CR/PC for Biomarker & ADA/NAb Assays

  • Topic 8:

    Enhanced Approaches for Conducting a Comprehensive Characterization of LBA Critical Reagents (CR) to Guarantee High Quality: Biophysical/biochemical techniques for CR in support development of robust LBA, key stress studies for ensuring stability, characterization of ligands multiple lots in early development to guarantee consistency, identification of ligand-binding domain to the antibodies as crucial for Biomarker Assays
    Dr. Kun Lu, Associate Director, Critical Protein Reagent Group, Regeneron

  • Topic 9:

    Specific Deep Critical Reagents (CR) Characterization for NAb LBA to Ensure Successful and Fast Method Development: What are the Regulatory Expectations for NAb LBA critical reagent characterization during development? When is it necessary to go beyond Concentration assessment, Purity determination and Minimal Determination of Functionality (CPF) to assess CR when developing complex NAb LBA?
    Dr. Kimberly Reese, Associate Director, GlaxoSmithKline

  • Topic 10:

    Key Consideration to Generate Suitable Surrogate Positive Controls (PC) to Enable Smooth ADA LBA Development/Validation: Problems with scarce literature for PC, approaches for generation of cross-reactive polyclonal/monoclonal antibodies through animal immunization as positive controls, critical reagents for ACE ADA assay format as effective platform for siRNA immunogenicity assessment
    Dr. Yi Wen, Senior Director, Clinical Immunogenicity, Eli Lilly and Co.

Session 4: State-of-the-art Integrative Bioanalysis by Leveraging Multiple Platforms: LBA, Mass Spec and PCR

  • Topic 11:

    State-of-the-art Concepts of Integrative Bioanalysis by Leveraging Multiple Platforms: Answering complex questions on new modalities with orthogonal approaches, evaluating when to include multiple methods in Regulated Bioanalysis and how to integrate datasets for a cohesive analysis, Complementarity of LBA, Mass Spec & PCR for systematic assessment of matrix effects, non-viral GT, investigate ADC immunogenicity
    Dr. Samuel Pine, Global Head of Bioanalysis & Immunogenicity, DMPK, Sanofi

  • Topic 12:

    Advanced Multiple Platform Approaches to Nonclinical & Clinical PK Bioanalysis of Masked Cytokines: Measurement of prodrug, active, and mask by comparing LBA & Mass Spec data, focus on the strategies to address pro-drug interference, reagent strategy to deliver on sub-ng/mL clinical sensitivity requirements by smart frontloading, early regulatory engagement to understand what PK measurements should be conducted
    Ms. Kelly Coble, Director of Bioanalytical Sciences, Boehringer Ingerheim

  • Topic 13:

    Advantages of N-Plex LBA in the Complex Bioanalysis of RNAi and use of Multiple Platforms offering advantages and disadvantages: Comparison of nucleic acid detection N-Plex LBA platform vs traditional stem-loop qPCR, focus on quantification of deaminated siRNA metabolites in tissues and limitations of qPCR, novel N-Plex LBA challenges and opportunities for analysis of study samples for siRNA levels
    Dr. Valerie Clausen, Director, Bionalytical Sciences, Alnylam

Session 5: 2024 White Paper in Bioanalysis

  • 2024 White Paper on Advanced Strategies for Ligand-Binding Assays

    Consensus & Conclusions on Advanced Strategies for Ligand-Binding Assays for 2024 White Paper

Agenda at a Glance Agenda at a Glance