Adaptation of Commercial Biomarker Kits and Proposal for ‘Drug Development Kits’ to Support Bioanalysis: Call for Action

A multiplicity of issues surround the biomarker assay validation (BAV) for clinical trial use and regulatory submission. These issues extend from diverse analytical considerations due to the array of molecular types, sizes and end use purposes coupled with an extraordinary range of expressed concentrations to lack of regulatory guidance/guideline specifically designed for the validation of biomarkers used in drug development. An attempt to regulate BAV was done with the US FDA 2013 draft guidance for industry bioanalytical method validation [1]. However, a AAPS/FDA workshop on this draft guidance concluded that "PK assays are not Biomarker assays" [2]. Hence, all the above issues on BAV are producing the appearance of a problem with an intractable solution.Though many valuable and contributory white papers have been issued [3][4][5][6][7][8][9], there are still continuing queries as to the veracity of individual methodologies corresponding to each individual facet of the BAV conundrum. However, as you can see from these white papers [3][4][5][6][7][8][9] spanning more than 10 years (2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017), the issues of BAV have evolved year after year, reflecting significant changes in thought-provoking chemotypes, steady advances and innovations in analytical technologies and a much more thorough questioning proposed in support of precision medicine. To this point, the discrepancy between the specialized information obtained by diverse technologies (such as LBA, LCMS and hybrid ligand-binding assay [LBA]/LCMS) leads automatically to disparate needs for validations tailored specifically first to the context of use of the target molecule and then to the constraints of the particular analytical technology [8,9]. In order to explore these concerns, this special focus issue of Bioanalysis has been dedicated to the BAV and shares with the reader scientific insights, regulatory opinions and relevant case studies of the current processes and industry standards. Moreover, this is a timely and fortuitous happenstance as a recent regulatory initiative [10] and has led to a more harmonized perception of the gaps and necessities of both the BAV and the essential prerequisites for biomarker qualification [11].In an editorial, L Stevenson (Biogen) discusses the critical concepts associated with parallelism assessments in LBA-biomarker assay development and the BAV, which has been an increasingly debated and a popular topic of discussion over recent years in the literature. Here, the key discussion points on this important topic covered in recent public workshops in the USA are described [12].The current situation on BAV in another of the major countries involved in drug development, Japan, is discussed in this issue in an editorial by Saito et al. (NIH Sciences). This is an important topic for the Japanese scientific community, since as previously mentioned, there is a risk that the acceptance criteria described in the BMV guidance/guidelines for PK assays, from the Japanese MH...

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confidence: 99%

Biomarker Assay Validation

Piccoli¹,

Garofolo

2018

“…Bowsher et al called for 'pharmaceutical grade kits' that would comply with clear criteria and documentation that are suitable for use in a regulated environment [17]. Islam et al proposed a three-tiered approach to 'drug-development kits' with clearly defined quality attributes that can be adapted to perform fit-forpurpose (FFP) analytical validation in a regulated environment [18]. While some commercial kit manufacturers have begun to classify their kits according to higher levels of characterization (e.g., 'V-plex' from MesoScaleDiscovery, 'regulated kits' from Somru Bioscience, Inc.), there has not been an industry-wide effort between manufacturers and the end users to improve the overall quality of kits for use in drug development.…”

Section: Introductionmentioning

confidence: 99%

Recommendations for Classification of Commercial LBA Kits for Biomarkers in Drug Development From the GCC for Bioanalysis

Islam

Kar

Ritzén³

et al. 2019

Self Cite

Over the last decade, the use of biomarker data has become integral to drug development. Biomarkers are not only utilized for internal decision-making by sponsors; they are increasingly utilized to make critical decisions for drug safety and efficacy. As the regulatory agencies are routinely making decisions based on biomarker data, there has been significant scrutiny on the validation of biomarker methods. Contract research organizations regularly use commercially available immunoassay kits to validate biomarker methods. However, adaptation of such kits in a regulated environment presents significant challenges and was one of the key topics discussed during the 12th Global Contract Research Organization Council for Bioanalysis (GCC) meeting. This White Paper reports the GCC members' opinion on the challenges facing the industry and the GCC recommendations on the classification of commercial kits that can be a win-win for commercial kit vendors and end users.

Data Driven CRO Benchmarking for Biomarker Analysis

Dolman¹,

Yu²,

Gusev³

2020

Outsourcing is a common strategy across the pharmaceutical industry and clinical research. CROs offer many choices for selecting outsourcing partners for bioanalytical and biomarker support. We aimed this paper to provide critical insights into CRO benchmarking and selection using a bioanalytical challenge approach performing fit-for-purpose ligand-binding assay. Bioanalytical challenge (method validation and sample analysis) offer Pharma sponsors a great opportunity to stress test CRO technical and scientific competency, quality systems and operational capabilities. In addition, CROs demonstrated their real-life performance in communication, time management and cost – key contributors to a successful sponsor-CRO partnership. Benchmarking CROs based on objective assay data and real-life experiences will help sponsors to make better-informed decisions in vendor selection.