Bioanalytical Method Validation for Macromolecules in Support of Pharmacokinetic Studies

Smolec, JoMarie; DeSilva, Binodh; Smith, Wendell C.; Weiner, Russell; Kelly, M Ramzy; Liu, Ben; Khan, Masood; Tacey, Richard; Hill, Howard; Celniker, Abbie; Shah, Vinod P.; Bowsher, Ronald R.; Mire‐Sluis, Anthony R.; Findlay, J. W. A.; Saltarelli, Mary; Quarmby, Valerie; Lansky, David M.; Dillard, Robert F.; Ullmann, Martin; Keller, Stephen; Karnes, H. Thomas

doi:10.1007/s11095-005-5917-9

Cited by 97 publications

(50 citation statements)

References 2 publications

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“…Performance characteristics of ligand binding assay (LBA) components which include but are not limited to the solid or immobilized surfaces such as microtiter plates and the capture and detection antibodies should be thoroughly evaluated in the method development phase, and appropriate plans should be put in place to monitor lot to lot reagent consistency. The general requirements for the design of calibration curves, the acceptance criteria for individual calibrators, and the guidelines for the selection of an appropriate regression model have been defined in regulatory guidance documents and lead publications by subject matter experts (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Compliance with these guidelines and adherence to the published requirements would enhance reproducibility of a calibration curve across runs and across studies.…”

Section: Introductionmentioning

confidence: 99%

Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves

Azadeh

Gorovits

Kamerud

et al. 2017

AAPS J

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Abstract.The accuracy of reported sample results is contingent upon the quality of the assay calibration curve, and as such, calibration curves are critical components of ligand binding and other quantitative methods. Regulatory guidance and lead publications have defined many of the requirements for calibration curves which encompass design, acceptance criteria, and selection of a regression model. However, other important aspects such as preparation and editing guidelines have not been addressed by health authorities. The goal of this publication is to answer many of the commonly asked questions and to present a consensus and the shared views of members of the ligand binding assay (LBA) community on topics related to calibration curves with focus on providing recommendations for the preparation and editing of calibration curves.

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Section: Introductionmentioning

confidence: 99%

Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves

Azadeh

Gorovits

Kamerud

et al. 2017

AAPS J

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“…It is for this reason that most bioassays are best used semiquantitative to monitor longitudinal trends through the course of a treatment and to measure relative changes and fold-differences, making the rigorous validation parameters developed for quantitative pharmokinetic assays redundant. We have taken a pragmatic approach based on ''fit for purpose'', assessing the parameters and level of validation by the purpose of the assay and the final use of the data collected, to determine whether verification or evaluation of the assay is acceptable (19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Enumeration and phenotypic assessment of human plasmacytoid and myeloid dendritic cells in whole blood

2010

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Traditionally, flow cytometry analysis of dendritic cells (DC) has followed a negative selection procedure, often limiting the characterization of individual DC subsets to enumeration. We demonstrate the development, evaluation, and clinical application of a novel 6 color/8 parameter flow cytometry panel to allow enumeration and monitoring of activation status of circulating human myeloid (MDC1) and plasmacytoid (PDC) dendritic cells in human whole blood. Enumeration showed a trend of greater numbers of MDC1s and PDCs being collected for fresh whole blood than frozen PBMCs, with this difference being statistically significant (P ¼ 0.04) for unstimulated PDC enumeration. Intra-assay variation had a coefficient of variation <10% and interassay results between operators showed good correlation (r > 0.95). Our results on fresh whole blood showed a significant up regulation of CD83 on both MDC1 and PDC at 4 h post Toll-like ligand stimulus and this activity was comparable in frozen PBMC samples. Comparison for the late activation marker CCR7 showed a significant difference (P < 0.05) in expression between fresh and frozen samples, precluding its use for batch analysis of frozen samples. In addition, the level of activation is dependent on the anticoagulant used for sample collection. For CD83 expression at 4 h both EDTA and lithium heparin samples are comparable for MDC1 and PDC populations. Whereas for CCR7 expression, lithium heparin is preferable as EDTA increases the background expression in PDC, preventing further functional assessments. We demonstrate the importance of establishing the kinetic profile of activation marker expression and the importance of evaluating sample collection tubes and sample type before application of novel cytometry panels to a clinical study. We have shown that this DC enumeration flow cytometry panel is a robust analysis system that allows the flexibility of including activation markers. '

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“…Validation approaches for quantitative bioanalytical methods are available in regulatory guidance documents and other publications (1)(2)(3)(7)(8)(9). The guidance documents emphasize the need to characterize potential assay interferences from metabolites, degradation products and concomitant medications during validation.…”

Section: Understanding Pk and Immunogenicity-regulatory Expectations mentioning

confidence: 99%

A White Paper—Consensus and Recommendations of a Global Harmonization Team on Assessing the Impact of Immunogenicity on Pharmacokinetic Measurements

Sailstad¹,

Amaravadi

Clements-Egan

et al. 2014

AAPS J

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Abstract. The Global Bioanalysis Consortium (GBC) set up an international team to explore the impact of immunogenicity on pharmacokinetic (PK) assessments. The intent of this paper is to define the field and propose best practices when developing PK assays for biotherapeutics. We focus on the impact of anti-drug antibodies (ADA) on the performance of PK assay leading to the impact on the reported drug concentration and exposure. The manuscript describes strategies to assess whether the observed change in the drug concentration is due to the ADA impact on drug clearance rates or is a consequence of ADA interference in the bioanalytical method applied to measure drug concentration. This paper provides the bioanalytical scientist guidance for developing ADA-tolerant PK methods. It is essential that the data generated in the PK, ADA, pharmacodynamic and efficacy/toxicity evaluations are viewed together. Therefore, the extent for the investigation of the PK sensitivity to the presence of ADA should be driven by the project needs and risk based.

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Bioanalytical Method Validation for Macromolecules in Support of Pharmacokinetic Studies

Cited by 97 publications

References 2 publications

Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves

Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves

Enumeration and phenotypic assessment of human plasmacytoid and myeloid dendritic cells in whole blood

A White Paper—Consensus and Recommendations of a Global Harmonization Team on Assessing the Impact of Immunogenicity on Pharmacokinetic Measurements

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