2015 White Paper on Recent Issues in Bioanalysis: Focus on New Technologies and Biomarkers (Part 3 – Lba, Biomarkers and Immunogenicity)

Abstract

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5 day, week-long event - A Full Immersion Bioanalytical Week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS and LBA approaches, including the focus on biomarkers and immunogenicity. This 2015 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 2015 edition of this comprehensive White Paper has been divided into three parts. Part 3 discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Part 1 (small molecule bioanalysis using LCMS) and Part 2 (hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in volume 7, issues 22 and 23 of Bioanalysis, respectively.

Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial

“…16 The cutoff point for this assay was determined statistically with a false positive rate of 5%, and so the ADA positive rate observed at screening in this study was within the range of false positivity anticipated by Amaravadi et al (2–11%). 17 In this study, confirmatory and titration methods were improved by using ofatumumab, another anti-CD20 antibody, which reduced potential interference of circulating CD20 CMFs by preventing the binding of CD20 in the sample to labelled rituximab reagents in the assay. However, further non-specific binding by other unknown factors remains possible.…”

The Decennial Index of The White Papers in Bioanalysis: ‘A Decade of Recommendations (2007–2016)’

“…Precision and accuracy of a biomarker assay should be assessed. However, when the biomarker methods are relative quantitative or qualitative, assay validation efforts should be focused on assay precision or reproducibility [13]. Discussions regarding BAV continued in 2016 and recommendations were similar to those from the previous year; stability recommendations evolved and were expanded [16].…”

“…Biomarker assay validation (BAV) requirements were deliberated in 2015, when it was established that exploratory and confirmatory biomarker categories are not always distinct. The application of an assay may evolve during the drug development and the levels of assay validation required may vary depending on the intended use of the data [13]. Due to a variety of challenges, developing and validating the biomarker assay cannot always be performed to meet the standards of a PK assay as requested by the 2013 US FDA draft guidance.…”

“…Based on industry and regulatory experience reported in 2015, both one-assay and two-assay approaches for the demonstration of clinical immunogenic comparability for biosimilars were considered valid approaches and accepted by regulatory agencies [13]. However, it was recommended during the 2016 Workshop that one assay is preferred in which the biosimilar is used as both the capture and detector reagent [16].…”

“…The approach should be data driven, and determined on acquired validation data. Whenever possible, matrix pools from both healthy and patient populations should always be included in the biomarker validation [13]. For biomarkers, it was further determined in 2016 that it is not necessary to monitor stability of both the spiked analytical QCs and endogenous sample QCs.…”