Topic 1:

Development of Advanced ADA Assays for Non-clinical ADA Analyses: Issues with current paradigm for non-clinical ADA testing; How to address different situations in non-clinical programs, practicalities, lessons learned; Strategies for a quick & agile method development of highly drug- and target-tolerant methods; Challenges of generic assays for protein therapeutics by LBA and Hybrid Assays; Hurdles, different settings pros & cons for Single-tier testing approach. 

Topic 2:

Challenges in Interpretation of Immunogenicity Results for Biosimilars: Benefits of Integrated Summary of Immunogenicity (ISI); How ISI and Immunogenicity Risk Assessment (IRA) facilitate Regulatory Agencies' review/feedback; ISI as advanced tool to explain ADA/NAb impact on PK/PD, efficacy and safety; ISI & IRA for next generation biosimilars supporting streamlined development focusing on analytical data in silico and in vitro tools to assess immunogenicity risk.

Topic 3:

Current Experience with Immunogenicity of ASOs, siRNAs and other Oligonucleotide-based Therapeutics: Challenges associated with ADA assay development and advanced strategies in overcoming those challenges; Understanding the recent Regulatory Expectations for immunogenicity assessments based on feedback on approved oligonucleotides based on the June 2024 FDA Guidance for industry; Recommendations for Immunogenicity assessment strategy to support oligonucleotide-based therapeutics in non-clinical and clinical studies.

Topic 4:

Development of Cell-Based Assay (CBA) to Assess Innate Immune Responses of Host Cell Proteins (HCP) in Recombinant Peptide Therapeutics: Potential impact of HCP on safety and efficacy and Regulatory Guidelines; Bioanalytical methods design & sensitivity to detect immune responses to HCP; 505(j) pathway for Generic Synthetic Peptides and proposal to use robust CBA to detect immune responses of HCP to file follow-on recombinant peptides and under 505(j).

Topic 5:

Importance of understanding the current issues with Lack of well-defined Gold Standards for Biomarker Calibrators: Variable level of characterization, purity, degree of control of lot changes; Need of lot-to-lot control by the user and Additional Parallelism Work; Biomarker Calibrators may not be identical in mass or form to measured analyte with significant issue for PD assays; Biomarker Calibrators may not measure the intended form of analyte impacting conclusions made with the data and dosing projection for target coverage.

Topic 6:

Ongoing Issues with Reference Standard Materials (RSM) for Biomarker Assays: Selecting RSM based on the biological properties of the analyte, stability, availability, well-characterized properties; Characterization process include: Identity, purity, affinity, stability, and Parallelism as functional performance in the assay parallelism; When Parallelism is more important than biological activity; Preparation and characterization of unusual reference materials; Evaluation and maintenance of lot-to-lot consistency. 

Topic 7:

Long-Term Stability of Biomarkers: Considerations for Assessment and Data Analysis: Assessing the stability of biomarker over time, key steps from sample collection, storage, baseline measurements, longitudinal analysis, controls used to ensure adequate assessment; What are the different approaches for designing stability studies and what can be feasible; Implications of not understanding the stability of the biomarker in supporting short-term and long-term clinical trials.

Topic 8:

US FDA's Final Rule and the Impact to Clinical Trial Testing Procedures and Practices: Historical FDA enforcement discretion over in vitro diagnostic tests developed and run within a single laboratory (Laboratory Developed Tests LDTs); Issuing of the Final Rule brings most LTDs under the same regulatory framework as Companion Diagnostics and in vitro Diagnostics and (CDx & IVDs); Needs for the Industry to be aware of, plan for, and mitigate the potential impacts of the Final Rule to the many tests used within drug clinical development.

Topic 9:

Shedding Assays when & how? Shedding via excreta (urine and feces), and secreta (saliva, semen, sweat) for non-replicating viruses: Can nonclinical shedding data be leveraged for clinical development? Can shedding data be leveraged across programs when route of administration/dose are the same? How much data is sufficient from clinical studies? USA vs Europe vs ROW: are there differences and if yes, why there should be?

Topic 10:

A Comprehensive look at the key Bioanalytical & Immunogenicity Endpoints when assessing mRNA-LNP Therapeutics Encoding Multiple Proteins; Streamlining LBA Method Development through Efficient Design; Address the complexities involved in generating Surrogate Reference Materials for distinct multi-domain mRNA-derived protein; Highlighting the role of LBA in detecting ADA against both mRNA-derived proteins and LNP; Crucial assessments for understanding potential impacts on therapeutic efficacy and safety.

Topic 11:

Current status of Development & Validation of NGS Assay for Gene & Cell Therapies & application in Bioanalytical field: Important factors to consider in developing NGS technologies; Leveraging integrative genomics combining biochemical, cell-based, and computational methods to evaluate efficacy and specificity in the pre-clinical context; Involving appropriate wet lab controls, data sets, software engineering & cloud computing for NGS pipeline qualification & data integrity.

Topic 12:

Advancements in Characterization of Cellular Kinetics and Biodistribution of Cryopreserved Allogeneic CAR-NK Cellular Therapy: Quantification of CAR-NK viral genome DNA copy number in mouse whole blood and tissues by ddPCR and soluble IL-15 in mouse plasma by LBA to support pharmacology and toxicology study; Difficulty to engineer CAR NK cells by requiring cytokine activation to enable tumor-killing ability and sufficient in vivo persistence.

Topic 13:

T Cell Response to support Immunogenicity Assessment using Validated Functional Assays by Flow Cytometry in Vaccine Clinical Trials: Challenges with PBMC preparation and processing issues preventing robust T Cell evaluation in pediatric studies; Novel application of Direct Whole Blood Stimulation at clinical site as alternative option; Overcoming issues of technology novelty, current limited knowledge on application to clinical studies and validation relevant parameters. 

Topic 14:

Strategies & Approaches to Validation of Flow Cytometry-based Cell-Mediated Immunity (CMI) Assays and its inherent challenges: How to identify appropriate sample panels with range of responses, procuring sufficient quantity of samples with characterized responses to antigens of interest; Challenges with cell mimics, surrogate cell lines (hybridomas, transfected/modified) or antigen surrogates (peptide pools, toxoids, proteins, mitogens); Use of PBMCs from vaccinated versus naturally exposed individuals.

2025 White Paper on Ligand-Binding, Cell-Based, and Molecular Assays

Consensus & Conclusions on Ligand-Binding, Cell-Based, and Molecular Assays for 2025 White Paper