2018 White Paper on Recent Issues in Bioanalysis: Focus on Flow Cytometry, Gene Therapy, Cut Points and Key Clarifications on Bav (Part 3 – Lba/Cell-Based Assays: Immunogenicity, Biomarkers and Pk Assays)

Abstract

The remaining list of author names, affiliations and Regulatory Agencies Disclaimer can be found at the end of the articleThe 2018 12 th Workshop on Recent Issues in Bioanalysis took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small-and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays. Part 1 (LCMS for small molecules, peptides, oligonucleotides and small molecule biomarkers) and Part 2 (hybrid LBA/LCMS for biotherapeutics and regulatory agencies' inputs) are published in volume 10 of Bioanalysis, issues 22 and 23 (2018), respectively.

2020 White Paper on Recent Issues in Bioanalysis: BAV Guidance, CLSI H62, Biotherapeutics Stability, Parallelism Testing, CyTOF and Regulatory Feedback ( Part 2A –Recommendations on Biotherapeutics Stability, PK LBA Regulated Bioanalysis, Biomarkers Assays, Cytometry Validation & Innovation Part 2B –Regulatory Agencies’ Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine)

“…The concepts and applications of COU and FFP BAV have been discussed in depth in the 2017, 2018, and 2019 White Papers in Bioanalysis [20,23,27]. How is COU being defined in industry and how does that definition impact BAV?…”

“…-Accuracy/relative accuracy -Parallelism -Measurement range -Precision -Repeatability -Reproducibility -Analytical specificity -Limits of detection/limits of quantitation -Stability Despite the call by industry to provide a BAV guidance [23], this regulatory guidance has yet to be released. However, for more than a decade, White Papers have been available in literature to begin to fill this gap [17,20,23,27,[30][31][32].…”

“…What experiments to perform and what acceptance criteria to apply for drug development assays has been an ongoing focus of the 2017-2019 White Papers in Bioanalysis [20,23,27]. Due to the importance of this topic, an entire workshop was dedicated at the 14 th WRIB as a training session for the Global Bioanalytical Community and to update the audience on advances in the practical application of FFP BAV and COU in defining what aspects of validation to pursue and what acceptance criteria to set across both sets of technologies, noting the overlap and differences.…”

Next‐Generation DILI Biomarkers: Prioritization of Biomarkers for Qualification and Best Practices for Biospecimen Collection in Drug Development

“…For example, if a biomarker will be used for regulatory decision making, then full assay validation is required. [54][55][56] The framework includes (i) describing the drug development need, (ii) defining COU, (iii) considering potential benefits if the biomarker is qualified, and (iv) considering potential risks if the biomarker is used in a clinical development program.…”

2019 White Paper On Recent Issues in Bioanalysis: FDA BMV Guidance, ICH M10 BMV Guideline and Regulatory Inputs ( Part 2 – Recommendations on 2018 FDA BMV Guidance, 2019 ICH M10 BMV Draft Guideline and Regulatory Agencies' Input on Bioanalysis, Biomarkers and Immunogenicity)

“…Therefore, demonstrating dilutional linearity is critical for reliable measurement of study samples. Industry best practices recommend that high concentration sample(s) be prepared in matrix at concentrations above the assay range, including at the anticipated C max or the highest possible concentration that can be achieved with the available reference standard while maintaining 95% matrix [9,12,15,18,21,62]. These samples are serially diluted to cover the entire quantitation range.…”