2014 White Paper on Recent Issues in Bioanalysis: A Full Immersion in Bioanalysis (Part 2 – Hybrid LBA/LCMS, ELN & Regulatory Agencies’ Input)

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 2) covers the recommendations for Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input. Part 1 (Small molecules bioanalysis using LCMS) was published in the Bioanalysis issue 6(22) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the Bioanalysis issue 6(24).

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

“…In 2014, it was recommended that for successful design and implementation of ELNs, consideration should be given on how the ELN will be integrated with instruments, LIMS and other databases in the laboratory, how it will be reviewed by supervisors and QA, how interim and regulatory reports will be prepared, how archiving will be managed and how the regulators can inspect the data via the ELN. Close collaboration with IT specialists was considered crucial [9]. In 2016, prior recommendations regarding the use of ELN were still considered valid.…”

“…It was not generally recommended to measure an analyte with both approaches; however, this may happen when one assay or technology runs into issues such as matrix interference, when early data are generated on one platform and then the platform is switched to the other; or when the molecular complexity necessitates additional characterization. When cross-validating between LCMS and LBA, QC samples and incurred samples should be used, and the general acceptance criteria that should be applied are twothirds of sample results within 30% [9]. The following year, this recommendation was expanded to conclude that if cross-validation of LBA and LCMS data are required, then it is recommended to use the same capture reagent [12].…”

“…The main challenges for ADC bioanalysis discussed in 2014 included heterogeneity of the reference material containing molecules with different drug-antibody ratios, changing ADC composition in biological samples future science group Special Feature Garofolo & Savoie and availability of the adequately characterized reference materials for all the molecular species with different drug-antibody ratios. The complexity of ADCs requires multiple bioanalytical methods including mAb assays, unconjugated payload LCMS assays and ADC conjugate assays [9]. As the content of the conjugated payload in ADCs is typically vastly higher than the concentrations of the unconjugated payload in matrix, it could be challenging to prevent the cleavage of ADCs and artificial formation of unconjugated payload during in vivo sample collection, processing and analysis.…”

“…For quantification of ADCs, LCMS assays may be more sensitive and selective. They may be applicable to different ADCs with similar payloads, and they often require less time for method development and validation [9].…”

“…One particular approach that may be suitable for the analysis of membrane proteins employs tissue disruption and harsh denaturing c onditions for extraction followed by p roteolytic digestion prior to LCMS analysis [9].…”