Large Molecule Specific Assay Operation: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

Stevenson, Lauren; Kelley, Marian; Gorovits, Boris; Kingsley, Clare; Myler, Heather; Österlund, Karolina; Muruganandam, Arumugam; Minamide, Yoshiyuki; Domínguez, M.

doi:10.1208/s12248-013-9542-y

Cited by 24 publications

(15 citation statements)

References 15 publications

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“…The conclusions obtained from this study are entirely consistent with most current thinking on %AR calculations for adjusting endogenous biomarker content in spiked VS and selectivity samples (22,23). Accordingly, it is preferable to make these calculations by subtracting the endogenous component first, followed by determining the analytical recovery of the spike reference material fraction.…”

Section: Relationships Between the Present Findings And Other Publishsupporting

confidence: 82%

“…We consider the subtraction method preferred over that of addition to adjust for detectable endogenous biomarker levels in %AR calculations, consistent with opinions of others (e.g., [9][10][11][12][13]20,22,23). The subtraction method can use either mass units or raw assay signal, the latter of which being applicable when the endogenous analyte is present above the LOD, but BLOQ.…”

Section: Discussionsupporting

confidence: 64%

“…Specifics about %AR calculations were not substantially discussed in the recently released 2013 BMV draft guidance, nor the Crystal City V workshop report (18). Thus, while there are published white papers specifying the use of subtraction in selectivity assessments (22,23), the message is not being effectively delivered.…”

Section: Relationships Between the Present Findings And Other Publishmentioning

confidence: 99%

“…Physical means have been proposed to deal with matrix effects, including increasing the MRD and use of stripped or immunodepleted matrix. Matrix effects and means to address issues with endogenous biomarker levels have been discussed in detail elsewhere (1,3,20,23).…”

Section: Relationships Between the Present Findings And Other Publishmentioning

confidence: 99%

“…Nevertheless, influential publications support use of the subtraction method (e.g., [19][20][21]. Moreover, recent white papers on biomarker BMV by the Global CRO Council and by the Global Bioanalysis Consortium Harmonization Team state that the subtraction method should be used for adjusting endogenous biomarker content in selectivity determinations (22,23).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Relationships Between the Present Findings And Other Publishsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 64%

Section: Relationships Between the Present Findings And Other Publishmentioning

confidence: 99%

Section: Relationships Between the Present Findings And Other Publishmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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Pharmacokinetic Profiles of a Proposed Biosimilar Ustekinumab (BFI‐751): Results From a Randomized Phase 1 Trial

Hausfeld,

Challand,

McLendon

et al. 2023

Clinical Pharm in Drug Dev

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BioFactura has developed a proposed biosimilar candidate (BFI‐751) to ustekinumab reference product. Results are reported for the first‐in‐human trial designed to compare the pharmacokinetic profiles, safety, and immunogenicity of BFI‐751 and ustekinumab reference products from the European Union and United States as well as similarity of the EU and US reference products. This was a multicenter, randomized, double blind, 3‐parallel‐group study (trial ID: NCT04843631). Healthy subjects were randomized to receive a single subcutaneous dose of 45 mg of BFI‐751, EU ustekinumab, or US ustekinumab. The pharmacokinetic parameters were area under the concentration–time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum concentration. Safety, tolerability, and immunogenicity data were also reported. Pairwise comparisons among the 3 treatments all met the standard bioequivalence criteria that the 90% confidence interval of the geometric mean ratios of AUC from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum concentration are completely within the acceptance interval of 80.00%–125.00%. There were no marked differences in the safety and tolerability profiles for subjects receiving BFI‐751 as compared to EU or US ustekinumab. Treatment‐emergent adverse events were mild to moderate for all treatment groups.

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An Introduction to Bioanalysis of Bispecific and Fusion Proteins

Covert

Niu²,

Bhardwaj³

2022

An Introduction to Bioanalysis of Biopharmaceuticals

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Large Molecule Specific Assay Operation: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

Cited by 24 publications

References 15 publications

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

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

Pharmacokinetic Profiles of a Proposed Biosimilar Ustekinumab (BFI‐751): Results From a Randomized Phase 1 Trial

An Introduction to Bioanalysis of Bispecific and Fusion Proteins

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