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)

Abstract

The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA on 1–5 April 2019 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event – a full immersion week of bioanalysis, biomarkers, immunogenicity and gene therapy. 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, LBA cell-based/flow cytometry assays and qPCR approaches. This 2019 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 2019 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on the 2018 FDA BMV guidance, 2019 ICH M10 BMV draft guideline and regulatory agencies' input on bioanalysis, biomarkers, immunogenicity and gene therapy. Part 1 (Innovation in small molecules and oligonucleotides and mass spectrometry method development strategies for large molecules bioanalysis) and Part 3 (New insights in biomarker assay validation, current and effective strategies for critical reagent management, flow cytometry validation in drug discovery and development and CLSI H62, interpretation of the 2019 FDA immunogenicity guidance and gene therapy bioanalytical challenges) are published in volume 10 of Bioanalysis, issues 22 and 24 (2019), 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)

“…This topic is still being discussed over a decade later. In 2019, an extensive industry/regulators' discussion was had in the context of providing feedback for the upcoming ICH M10 guideline [26], and both positions described above were represented. Since no concrete data were available at the time to support either position, the recommendation that the lower temperature evaluation was not required if stability at a higher temperature was supported.…”

“…During the 2019 WRIB discussion [25,26], the point was made that the "30% criterion is rubbish." What can be done from a regulatory perspective?…”

“…The 2019 White Paper in Bioanalysis [26] provided recommendations for the performance of parallelism and discussed the 30% CV criterion used for parallelism required by the ICH M10 draft guidance [56]. The 2020 consensus is built on the 2019 framework and further developed and focused on providing more detailed and practical recommendations for parallelism in PK LBA validation.…”

“…The investigation involved testing several perpetrators, their effects on various analytes in buffer and plasma and their impact on accuracy and precision. Preliminary results were presented at the 13th WRIB [26]. In preliminary experiments, the effects of different mobile phases and lipemia on rivaroxaban and warfarin were examined.…”

2020 White Paper on Recent Issues in Bioanalysis: BMV of Hybrid Assays, Acoustic MS, HRMS, Data Integrity, Endogenous Compounds, Microsampling and Microbiome ( Part 1 –Recommendations on Industry/Regulators Consensus on BMV of Biotherapeutics by LCMS, Advanced Application in Hybrid Assays, Regulatory Challenges in Mass Spec, Innovation in Small Molecules, Peptides and Oligos)

“…What is the scientific and regulatory justification for the use of hybrid assays in clinical applications: unique biotherapeutic modality; lack of appropriate reagents for LBA; matrix interference (ADA, drug, endogenous proteins); in vivo drug instability / catabolism; and overall unsatisfactory performance of LBA? Does it still make sense to only add the minimum requirements for a hybrid assay in the ICH M10 Draft Guideline [26], as recommended in the 2019 White Paper in Bioanalysis [24], or is the industry ready for more extensive requirements? After one year, do we still agree that due to the increased complexity of hybrid assays, the LBA acceptance criteria of 20%/25% for precision and accuracy, and 30% for incurred sample reanalysis (ISR) criteria should be adopted for most protein, soluble target and antibody quantification?…”