Strategies to minimize variability and bias associated with manual pipetting in ligand binding assays to assure data quality of protein therapeutic quantification

Pandya, Kinnari; Ray, Chad; Brunner, Laura; Wang, Jin; Lee, Jean W.; DeSilva, Binodh

doi:10.1016/j.jpba.2010.04.025

Cited by 38 publications

(15 citation statements)

References 5 publications

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“…A publication by Pandya et al has highlighted the impact of personnel and training on key method performance variables in LM bioana lysis [11]. Method performance is affected by the technical expertise of an analyst in several ways, including: n The technique of the analyst to pipette precisely as LBA methods use microliter volumes;…”

Section: Methods Transfer For Ligand-binding Assays: Recommendations Fmentioning

confidence: 99%

“…Through our experience with LBA method transfer over the years, dilutional accuracy and linearity have proven to be key parameters to confirm acceptable performance at laboratory 2. Any bias due to pipetting techniques can cause loss of accuracy and linearity [11]. Dilutional accuracy is also controlled during production with the inclusion of dilutional QC runs, at least to the highest dilution factor used for sample ana lysis.…”

Section: Troubleshooting: a Logicalmentioning

confidence: 99%

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Method Transfer for Ligand-Binding Assays: Recommendations for Best Practice

et al. 2011

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To support clinical trials, bioanalytical methods are often transferred from one laboratory to another. With the rising number of large-molecule therapeutic proteins submitted for US FDA approval, the demand for large-molecule bioanalytical support and, subsequently, method transfer increases. Ligand-binding assays are the methods most commonly used to quantify endogenous and therapeutic proteins for the assessment of biomarkers and pharmacokinetic parameters. The goal of this review is to provide an overview of ligand-binding assay method transfer, essential parameters for partial method validation and to lay out a strategy to increase the chance of success. The recommendations herein are based on a summary of current publications and the authors' specific experiences, to help increase workload efficiency, maintain positive collaborations with partners and meet program timelines.

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Section: Methods Transfer For Ligand-binding Assays: Recommendations Fmentioning

confidence: 99%

Section: Troubleshooting: a Logicalmentioning

confidence: 99%

Method Transfer for Ligand-Binding Assays: Recommendations for Best Practice

et al. 2011

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“…High sample dilution can increase assay variability (18). Therefore, improvement with the in-house method was required for linearity over a wider analytical assay range.…”

Section: Linearity and Analytical Comparison Of Formulation Lots A And Bmentioning

confidence: 99%

Specific Method Validation and Sample Analysis Approaches for Biocomparability Studies of Denosumab Addressing Method and Manufacture Site Changes

Pourvasei

Lee

Eschenberg

et al. 2012

AAPS J

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Abstract. Manufacturing changes during a biological drug product life cycle occur often; one common change is that of the manufacturing site. Comparability studies may be required to ensure that the changes will not affect the pharmacokinetic properties of the drug. In addition, the bioanalytical method for sample analysis may evolve during the course of drug development. This paper illustrates the scenario of both manufacturing and bioanalytical method changes encountered during the development of denosumab, a fully human monoclonal antibody which inhibits bone resorption by targeting RANK Ligand. Here, we present a rational approach to address the bioanalytical method changes and provide considerations for method validation and sample analysis in support of biocomparability studies. An updated and improved ELISA method was validated, and its performance was compared to the existing method. The analytical performances, i.e., the accuracy and precision of standards and validation samples prepared from both manufacturing formulation lots, were evaluated and found to be equivalent. One of the lots was used as the reference standard for sample analysis of the biocomparability study. This study was sufficiently powered using a parallel design. The bioequivalence acceptance criteria for small molecule drugs were adopted. The pharmacokinetic parameters of the subjects dosed with both formulation lots were found to be comparable.

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“…Automation has been recommended in both the literature and public forums as a way to reduce variability [18][19][20][21]. However, liquid handlers only perform consistently if operating parameters are optimized for the specific diluent and sample matrix.…”

mentioning

confidence: 99%

“…Dilution error contributes directly to both bias in individual measurements and replicates variability in addition to other sources of error mentioned above [22,20].…”

mentioning

confidence: 99%