Specialized Workshop T1 - Tuesday May 07, 2024: 7am to 5:45pm - Discussion Topic List

"Advanced Strategies for Mass Spectrometry Assays"

Mass Spec Applications of Novel Modalities; Solving New & Old Challenges with Mass Spec Innovative Approaches in Small Molecules, Peptides, Oligonucleotides and Large Molecules/ADC Method Development/Validation; Lesson Learned from Mass Spec Technology Advancements in Discovery Bioanalysis; Recent Developments in Tissues/Non-Liquid Matrices; Novel Advancements in Intact Protein Bioanalysis and Sample Preparation/Immunoaffinity (IA), QTOF/Orbitrap Bioanalysis; Mass Spectrometry for Biomarker Discovery; Application of Discovery Bioanalysis Solution in Regulated Bioanalysis

Session 1: Biomarker Assays Advanced Strategies for Method Development/FFP BAV: FFPE Tissue, GIP Panel and Low Abundant Proteins

  • Topic 1:

    Targeted Protein Analysis Strategy for FFPE Tissue and Laser Capture Micro-Dissected Material by HRMS: Approaches to make FFPE analysis as quantitative as possible adapting Regulated Bioanalysis concepts for FFP Validation, PA with typical QC levels, IS variability, chromatographic interference, carryover, consistent duplicate extractions, variable analyte recovery depending on the extraction scale
    Mr. John Meissen, Associate Director, Biomarker Development, Astra Zeneca

  • Topic 2:

    Challenges Associated with Development of Gluten Immunogenic Peptides (GIP) Panel using Hybrid Assay (IA-MS) with emphasis on advanced Immunoaffinity (IA) based approach: Issues with the existence of many glutamines within a peptide sequence and long sequences, considerations with regards to FFP BAV design and implementation for clinical utilization, clinical/bioanalytical considerations on GIP as potential important biomarker for therapeutics targeting Celiac Disease
    Mr. Joe Palandra, Associate Director, Mass Spectrometry Clinical Bioanalysis, Takeda

  • Topic 3:

    Significant Challenges & Highlighted Strategies for De novo Development of Hybrid Assay (IA-MS) to Quantify Low Abundant Endogenous Protein Biomarkers: Emphasis on matrix suitability/availability/selection, difference between the recombinant/endogenous protein, critical need to confirm the affinity of capture antibody, impact of potential PTMs/isoforms, use of multiple surrogate peptides until their suitability is confirmed
    Dr. Naiyu Zheng, Scientific Associate Director, Bristol Myers Squibb

Session 2: Hybrid Assays (IA-MS) for PK: Advanced Strategies for ADC, Glycoproteins, Biotransformation and ICH M10 FFP Validation

  • Topic 4:

    Development of Hybrid Assay (IA-MS) for Quantitation of High Mannose of Biotherapeutic Glycoproteins in human & animal fluids, Tissues, Vitreous/Aqueous Humor: Issues to conduct in vivo assessment of high mannose to determine its clinical relevance, MRM detection of multiple glycopeptides simultaneously, challenges with lack of stable isotope labeled glycopeptide IS, specific use of peak area ratios of each glycopeptide for improving assay performance
    Dr. Lawrence Linzhi Chen, Bioanalytical Group Leader & Senior Research Fellow, Boehringer Ingelheim

  • Topic 5:

    Sophisticated Utilization of FFP Validated Hybrid Assay (IA-HRMS) to Determine Impact of Biotransformation on Validated LBA: Additional HRMS data to determine active PK profile from LBA, complications to performing nonclinical to clinical translation of PK and clinical dose prediction for molecules susceptible to biotransformation, need for HRMS data to accurately describe PK of unique bispecific molecules which are not traditional IgGs
    Dr. Adam Vigil, Senior Director, Preclinical & Translational PK/PD, Regeneron
    Ms. Wei Wei, Senior Scientist, Boehringer Ingelheim

  • Topic 6:

    Current/Recurring Concerns about having Hybrid Assays (IA-MS) still not being part of ICH M10 BMV Regulatory Requirements: Understanding the major discrepancies between Hybrid Assays and LBA & LC-MS/MS platforms, current issues with loosely defined FFP Validation guidelines in both primary/secondary matrices, validation testing, criteria around the assessments, and inclusion or exclusion of stock stability, whole blood stability, recovery, lesson learned
    Dr. Megan Cooley, Associate Director, Bioanalytical Services, ICON

Session 3: New Small Molecules Challenges and Ultra Sensitivity Mass Spec in Discovery & Regulated Bioanalysis

  • Topic 7:

    Navigating through Small Molecules Bioanalytical Challenges in Discovery Bioanalysis by enabling Mass Spec-based High-Throughput Quantitation with Simple, Fast, Robust and Standardized Methods: Dealing with diverse compound structures, complex biological matrices, limited sample volumes, tight deadlines, streamlined and integrated solutions to address inefficiency and enable smooth tech transfer across labs to advance small molecules
    Dr. Estelle Maes, Director, Non-Regulated Bioanalysis, AbbVie

  • Topic 8:

    Latest Developments in Endogenous Small Molecule Biomarkers for Assessment of CYP3A Clinical Drug-Drug Interaction: Extensive/complex method development, optimization effort to minimize the assay interference from endogenous positional isomers, successful applications to human clinical trial to assess CYP3A induction and inhibition, assessing this biomarker capability for monitoring moderate or even weak induction and inhibition
    Dr. Yongjun Xue, Scientific Director, Bioanalysis, Bristol Myers Squibb

  • Topic 9:

    Ultra Sensitivity Mass Spec for very Low Dose in vivo studies for Small Molecules Compounds with Limited Exposure: Atypical mobile phase compositions, unique novel column characteristics, advanced Mass Spec optimization, complex method development, challenges in Discovery and Regulated Bioanalysis, extensive method development and optimization effort to maximize Sensitivity & Selectivity (S&S) and minimize matrix interference
    Ms. Elizabeth Hyer, Associate Director, Bioanalytical, Labcorp

  • Topic 10:

    Unique Method Development & FFP Validation of Small Molecule Biomarker Panels: Overcoming challenges with Glycosphingolipids, Eicosanoids and Amino Acid Biomarkers, how to multiplex related but different biomarkers, how to approach different dynamic ranges, ability of chromatography chemistries for short run times while separating closely related isomers, issues with RSM & IS and high endogenous levels in matrix
    Dr. Dawn Dufield, Scientific Officer, Mass Spectrometry, KCAS

Session 4: High Quality/Throughput Tissue Measurements to support Oligonucleotides and Biomarkers

  • Topic 11:

    High Demand for Mass Spec High Quality Tissue Target Measurements to support several Drug Modalities: Progress in tissue preparation strategies speed, accuracy, and transferability, lysing of perfuse and cryopulverized tissue, bead disruption and high speed centrifugation, normalization to total protein content and assaying consistent protein amount per well with calibrators, automating plate loading, washing, and elution to improves throughput
    Mr. Jay Johnson, Principal Scientist, Quantitative Biomarkers and Biomeasures, Pfizer

  • Topic 12:

    The always challenging Extraction Recovery in Mass Spec Bioanalysis of Fatty Acid Ligand Conjugated siRNA: Increasing the know-hows in support of regulated studies of siRNAs, Impact of ISTD on the curve linearity and assay performance, regression model, What is the best way to quickly identify a good analog ISTD for siRNA bioanalysis? Is better to use HRMS or Triple-Quad for siRNA bioanalysis? Considerations on the utility of both techniques
    Dr. Wenkui Li, Director, Bioanalytics, Novartis

  • Topic 13:

    Rare Tissues Quantitation Challenges in Mass Spec-based Oligonucleotides Bioanalysis: Purification challenges, ionization efficiency, additional experiments to demonstrate the equivalency of surrogate matrix, specificity, sensitivity, stability, matrix interference, incomplete extraction/degradation, considerations for siRNAs methods where both antisense strand (AS) and sense strand (SS) are simultaneously quantified in fluids and tissues for regulatory submissions
    Dr. Xiaonan Tang, Vice President, Bioanalytical Services, Frontage

  • Topic 14:

    Up-to-date Strategies for Development of Sophisticated Ultra-Sensitive Methods for Tissue Samples: Efficient homogenization approaches for different types of tissue, different sample preparation technologies especially hybridization extraction, various chromatographic approaches/columns, and models of mass spectrometry for ultra-low sensitivity
    Dr. Aihua Liu, Senior Director, Bioanalysis, Resolian

Session 5: 2024 White Paper in Bioanalysis

  • 2024 White Paper on Advanced Strategies for Mass Spectrometry Assays

    Consensus & Conclusions on Advanced Strategies for Mass Spectrometry Assays for 2024 White Paper

Agenda at a Glance Agenda at a Glance