Large Molecule Run Acceptance: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

Kelley, Marian; Beaver, Christopher; Stevenson, Lauren; Bamford, Ross; Gegwich, Paula; Yamamoto, Keiji; Li, Dongbei; Little, Samantha; Muruganandam, Arumugam; Stoellner, Daniela; Trivedi, Ravi

doi:10.1208/s12248-013-9553-8

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…For PK assays, typically three levels of QC (HQC, MQC, and LQC) which span the quantitative range of the assay are included for monitoring run performances (1,24). The accuracy of QC data is assessed using %RE with acceptance limits of ± 20%.…”

Section: Qc Performance Trendingmentioning

confidence: 99%

Quality Controls in Ligand Binding Assays: Recommendations and Best Practices for Preparation, Qualification, Maintenance of Lot to Lot Consistency, and Prevention of Assay Drift

Azadeh¹,

Sondag²,

Wang

et al. 2019

AAPS J

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Quality controls (QCs) are the primary indices of assay performance and an important tool in assay lifecycle management. Inclusion of QCs in the testing process allows for the detection of system errors and ongoing assessment of the reliability of the assay. Changes in the performance of QCs are indicative of changes in the assay behavior caused by unintended alterations to reagents or to the operating conditions. The focus of this publication is management of QC life cycle. A consensus view of the ligand binding assay (LBA) community on the best practices for factors that are critical to QC life cycle management including QC preparation, qualification, and trending is presented here. Electronic supplementary material The online version of this article (10.1208/s12248-019-0354-6) contains supplementary material, which is available to authorized users.

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Section: Qc Performance Trendingmentioning

confidence: 99%

Quality Controls in Ligand Binding Assays: Recommendations and Best Practices for Preparation, Qualification, Maintenance of Lot to Lot Consistency, and Prevention of Assay Drift

Azadeh¹,

Sondag²,

Wang

et al. 2019

AAPS J

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“…Sensitivity can be increased by including anchor points at the lower end of the calibration curve. Since anchor points should not be used in the assessment of the standard curve acceptance criteria, masking/exclusion criteria for anchor points are generally not addressed in guidance documents [31]. Having detailed SOPs to ensure an unbiased approach for masking of calibrators and anchor points is helpful to avoid observations and potential issuance of health agency findings.…”

Section: Anchor Pointsmentioning

confidence: 99%

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)

et al. 2019

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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.

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“…Lower limit of quantitation (LLOQ) is defined by the VS with the lowest passing concentration of analyte in regulated BMV (18,24,25). Less formal assay characterization protocols (variously termed exploratory, nonregulated, and method qualification) can use other means to define LLOQ as described in the BDiscussion^ (25)(26)(27).…”

Section: Relevant Bmv Detailsmentioning

confidence: 99%

“…Percent TE as used herein is the sum of inter-assay accuracy (percent relative error, %RE) plus inter-assay precision (percent coefficient of variation, %CV). Typical acceptance criteria are TE ≤30%, except at LLOQ where ≤40% is applicable (24). Percent spike was calculated by adding the nominal spike value with the mean endogenous concentration of the matrix blank control and dividing the nominal spike concentration by the total in the VS and multiplying by 100.…”

Section: Calculationsmentioning

confidence: 99%

Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation

Marcelletti¹,

Evans²,

Saxena

et al. 2015

AAPS J

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Abstract. It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

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Large Molecule Run Acceptance: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

Cited by 6 publications

References 5 publications

Quality Controls in Ligand Binding Assays: Recommendations and Best Practices for Preparation, Qualification, Maintenance of Lot to Lot Consistency, and Prevention of Assay Drift

Quality Controls in Ligand Binding Assays: Recommendations and Best Practices for Preparation, Qualification, Maintenance of Lot to Lot Consistency, and Prevention of Assay Drift

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)

Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation

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