Main Workshop DAY 2 - Wednesday April 3, 2019, 7am to 6:45pm

"LCMS & LBA, Common Topics, and Regulators Inputs DAY"

(You can click on each blue topic title below to see details, or simply scroll down to see details)

Day 2A: LBA & LCMS Orthogonality/Complementarity


Day 2B: ICH M10 BMV Draft Guideline - Common Topics Chromatography & LBA

Harmonized Topics among US FDA, EU EMA, Health Canada, Japan MHLW regulations

  • Topics will be announced once ICH Draft Guideline is Published

Unresolved Issues and On-going Industry/Regulators’ Discussions

  • Topics will be announced once ICH Draft Guideline is Published

Panel Discussion on ICH M10 BMV Draft Guideline Common Topics Chromatography & LBA

  • Industry Recommendations to ICH M10 Major Participating Regulatory Agencies

    • Dr. Brian Booth (US FDA / EWG Regulatory Chair)
    • Dr. Jan Welink (EU EMA / EWG Member)
    • Dr. Akiko Ishii (Japan MHLW / EWG Rapporteur)
    • Dr. Yoshiro Saito (Japan MHLW / EWG Member)
    • Dr. Anna Edmison (Health Canada / EWG Member)
    • Ms Thais Correa Rocha (Brazil ANVISA / EWG Member)


Day 2C: Regulators' Advice on Bioanalysis, BMV Guidance/Guidelines

Most Recent Regulators’ inputs on Bioanalysis, BMV Guidance/Guidelines

  • US FDA:

    Keynote: Updates on OSIS Inspections & Activities

  • UK MHRA:

    Transparency in Study Reporting: Inspections outcomes and issues with the final bioanalytical report

  • France ANSM:

    Validations Tests to Support Method Robustness Claim: How to Demonstrate to Regulatory Agencies Inspectors that your Assay is Robust

  • Health Canada:

    Regulatory Experience from Large Molecule Review

  • US FDA:

    Regulatory Science at CDER, US FDA

Ask the Regulators!
Traditional Interactive Panel Discussion with the Regulators on Bioanalysis, BMV Guidance/Guidelines

  • Regulatory Panelists:

    • Dr. Sean Kassim (US FDA), Dr. Sam Haidar (US FDA), Dr. John Kadavil (US FDA), Dr. Arindam Dasgupta (US FDA)
    • Dr. Brian Booth (US FDA), Dr. Nilufer Tampal (US FDA)
    • Dr. Jan Welink (EU EMA), Dr. Olivier Le Blaye (France ANSM), Mr. Stephen Vinter (UK MHRA), Ms. Emma Whales (UK MHRA)
    • Dr. Anna Edmison (Health Canada), Dr. Catherine Soo (Health Canada), Mr. Gustavo Mendes Lima Santos (Brazil ANVISA), Ms. Thais Correa Rocha (Brazil ANVISA)


Day 2D: Regulators' Advice on Immunogenicity Final Guidance and Biomarker Guidance/Papers

Most Recent Regulatory Inputs on Immunogenicity

  • US FDA:

    Interpretation & Implementation of the 2019 FDA Final Immunogenicity Testing Guidance: Focus on key Components of "Immunogenicity Testing of Therapeutic Protein Products - Developing and Validating Assays for Anti-Drug Antibody Detection Guidance"

  • EU EMA / Norway NoMA:

    Regulatory Observations from Submission of Biologics

  • Health Canada:

    Immunogenicity Clinical Relevance in Health Canada submissions

Most Recent Regulatory Inputs on Biomarkers

  • US FDA:

    Use of Biomarker Data in Support of Regulatory Submissions – a Clinical Pharmacology Perspective

  • UK MHRA:

    Updates on Predictive Biomarker-based Assay Development: UK MHRA Perspective

  • US FDA - Flow Cytometry:

    Pre-market Regulatory Review for Immunology and Flow Cytometry

  • US FDA - Flow Cytometry:

    Standardization Strategies in Flow Cytometry

Most Recent Regulatory Inputs on Gene Therapy


    Gene Therapy: Evaluation of Risk of Immunity and Current Regulatory Expectations

Ask the Regulators!
Traditional Interactive Panel Discussion with the Regulators on Immunogenicity Final Guidance and Biomarker Guidance/Papers

  • Regulatory Panelists on Immunogenicity:

    • Dr. Daniela Verthelyi (US FDA), Dr. Joao Pedras-Vasconcelos (US FDA), Dr. Haoheng Yan (US FDA)
    • Dr. Venke Skibeli (Norway NoMA), Dr. Therese Solstad Saunders (Norway NoMA)
    • Dr. Elana Cherry (Health Canada), Dr. Akiko Ishii (Japan MHLW)

  • Regulatory Panelists on Biomarkers:

    • Dr. Yow-Ming Wang (US FDA), Dr. Abbas Bandukwala (US FDA), Dr. Kevin Maher (US FDA), Dr. Shashi Amur (US FDA)
    • Dr. Shirley Hopper (UK MHRA)
    • Dr. Yoshiro Saito (Japan MHLW)

  • Regulatory Panelists on Gene Therapy:

    • Dr. Nirjal Bhattarai (US FDA CBER), Dr. Heba Degheidy (US FDA CBER)



Day 2A Details:
LBA & LCMS Orthogonality/Complementarity

LBA & LCMS Orthogonality/Complementarity

  • Topic 1
    Novel LBA & LCMS Combined Applications for Resolving Complex Bioanalytical Issues in Biotherapeutic Development: How LBA and LCMS can just go "hand in the hand" in advanced bioanalytical PK strategies
    • Understanding like LBA & LCMS data correlation can help better interpretation of
      • Biotherapeutics Exposure
      • Interpretation of the PK data
      • Dose-dependent PK exposure
      • Catabolism/metabolism
      • Complex biodistribution
      • Correlation to efficacy & safety
      • Stability
    • In vivo Biotransformation
      • LBA PK data
      • LCMS PK data correlation
      • Identification and quantification of biologically relevant catabolites/metabolites and impact on PK
    • Case studies and lesson learnt on how a combination of LBA, LCMS and Hybrid LBA/LCMS can help resolve complex bioanalytical issues
      • ADA impact on PK LBA & LCMS assay
        • Data comparison for better evaluation of exposure and clearance
      • Important applications of "reagents-free" LCMS methods
      • Advantages of LCMS vs Hybrid LBA/LCMS to avoid ADA and circulating binding interferences on immunoaffinity (IA) and LBA

  • Topic 2
    State-of-the-art Orthogonal LBA & LCMS Advanced Strategies for Biotherapeutics Bioanalysis in a Fully Integrated Bioanalytical Lab
    • Comprehensive bioanalytical strategy for a fully Integrated LBA & LCMS Bioanalytical Lab
      • Coordinated support for novel and complex biotherapeutics
      • Orthogonal LBA & LCMS approaches for maximizing the understanding of new modalities
    • Importance of overcoming the new bioanalytical challenges of novel biotherapeutic by combining and interpreting LBA & LCMS results
      • Learning how to correlate similar and/or different LBA & LCMS (and/or Hybrid LBA/LCMS) data in a combined approach
      • Orthogonal LBA & LCMS strategies to Investigate unusual Clinical PK
        • Updated recommendations on when LBA & LCMS show different results
        • Case studies: if LBA & LCMS do not agree, which is right?
        • LBA and LCMS assay full validation and data comparison
    • Advance use of “bottom up” (surrogate peptide), “top-down” (Intact mass and subunits) LCMS and functional LBA to understand biodistribution and catabolism/metabolism
      • Monitoring oxidation, deamidation and amino acid/subunits clipping
    • A combined bioanalytical LBA, LCMS and Hybrid LBA/LCMS approach for quantification of all relevant fractions (free, bound or total)
      • Assessment of active drug exposure
      • Hybrid LBA/LCMS ability to quantify free/active drug

  • Topic 3
    Tissue Protein Biomarkers Orthogonal LBA & LCMS Approaches for Correlation of Target Levels
    • Orthogonal LBA & LCMS quantitation for Tissue Protein Biomarkers
      • Challenges in quantitative analyses of tissue-bound proteins
      • Quantitative measurements when target is not soluble or readily shed
      • Challenges and Applications
      • Analytical considerations
    • Strategies for measuring antibody drug–target engagement in tissues
    • Correlation of Target Level Measured by LBA & LCMS orthogonal approaches
      • Total tissue target protein by LCMS
      • Combined LBA & LCMS information of target modification post dosing
      • Comparison of target level across species
      • Evaluation of target levels in human tumor samples
      • Importance of LBA & LCMS tissue data correlation for generation of meaningful data

  • Topic 4
    Assessing Tumor Microenvironment with Orthogonal/Complementary Bioanalytical Techniques: LBA & LCMS & Flow Cytometry
    • Importance of using orthogonal approaches to study Cancer Tissue Biomarkers
      • Case studies on a combined LBA, LCMS and Flow Cytometry approach
        • Hybrid LBA/LCMS methods to study tumor lysate stratification biomarkers, changes in analytes after treatment and frozen tissue section
        • Flow Cytometry assays for analysis of TILS (Tumor Infiltrating Lymphocytes) tumor cells and peripheral blood
        • LBA analysis of shed protein
      • Case studies where it was possible to detects analytes by multiple orthogonal technologies
      • Data correlation from multiple techniques for generation of meaningful conclusions
    • Combined Bioanalytical strategies to understand Tumor Microenvironment
      • Assessing tumor type selection and patient stratification
      • Method development and implementation
      • Complementarity of bioanalytical techniques in immuno-oncology and the evolving cancer biomarker landscape
    • Platform comparison for Tumor Biomarkers
      • Flow Cytometry, LBA, Hybrid LBA/LCMS
      • Potential issues in filing IND with a specific assay vs another?



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