2014 White Paper on Recent Issues in Bioanalysis: A Full Immersion in Bioanalysis (Part 3 – LBA and Immunogenicity)

Abstract

The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for Large molecules bioanalysis using LBA and Immunogenicity. Part 1 (Small molecules bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input) were published in the Bioanalysis issues 6(22) and 6(23), respectively.

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

“…At the 2014 Workshop, it was concluded that drug tolerance is a frequently encountered challenge among relatively high dosed therapeutics with a long half-life [10]. However, a great deal of progress had been made within the bioanalytical community in the previous decade concerning the technical hurdles, possibly due to the number of post-marketing requirements from health authorities, thus making drug tolerance a routine objective for all clinical testing.…”

“…It is likely that changes in PK profiles will occur as new, more specific critical reagents become available with the evolution of methods. It is not necessary to have the same result from different PK assays, but rather that there should be a scientific understanding of the species that the assays are measuring so that results can be interpreted appropriately [10]. Continued discussions in 2015 recommended that when there are differences in concentration future science group Special Feature Garofolo & Savoie results between two LBA platforms that had been previously cross-validated, an investigation would be needed to understand the reasons for the differences.…”

“…Routine assessment of ADA interference in PK assays was not recommended; however, it is important to understand the PK assay and to also consider data from other relevant assessments (e.g., PD and efficacy). Additionally, there is no need to routinely employ strategies to mitigate ADA interference, although there should be an understanding of how ADA may impact PK results [10].…”

“…The thinking following discussions in 2014 was that specificity testing should be conducted for each domain with a functional endpoint, for example, the antibody and payload. Further testing may be merited based upon a customized risk-assessment [10].…”

Ligand-Binding Assay Development: What Do You Want to Measure Versus What You Are Measuring?

“…During validation, understanding the effect of target interference and anti-drug antibodies (by utilizing a surrogate control) should be evaluated at a minimum. As bioanalytical scientists, we must strive to fully characterize our assays, to understand their strengths and limitations (14). While these experiments require time and often go above and beyond current regulatory requirements, the result will be robust bioanalytical methods with easily translatable and defendable data.…”