2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Challenging the Standard Immunogenicity Assessment Approach: 1-Tiered ADA Testing Strategy in Clinical Trials.

The ADA testing strategy for protein therapeutics was established almost two decades ago when assay methodologies were rudimentary, and serious immunogenicity-related safety issues had recently been observed with some biotherapeutics. The current testing paradigm employs multiple tiers and stringent cut points to minimize false negatives, reflecting a conservative stance towards ADA analysis. The development of highly sensitive ADA assay platforms and technologies such as humanized or fully human monoclonal antibody (mAb) drugs has put the traditional, resource-intensive 3-tiered testing approach under scrutiny.

Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis.

Background: Development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety.

Objective: To describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD).

Methods: This analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD.

A Contactless Low-Carbon Steel Magnetostrictive Torquemeter: Numerical Analysis and Experimental Validation.

Torque measurement is a key task in several mechanical and structural engineering applications. Most commercial torquemeters require the shaft to be interrupted to place the sensors between the two portions of the shaft where a torque has to be measured. Contactless torquemeters based on the inverse magnetostrictive effect represent an effective alternative to conventional ones.