A Step-wise Approach for Transfer of Immunogenicity Assays during Clinical Drug Development
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 3
Abstract
We designed a three-step statistical approach to transfer bioanalytical assays (ELISA and Biacore) which evaluates the (1) average equivalence between the two labs (2) concordance in individual sample results between the two labs, and (3) long-term stability of assay performance. Each experimental design evaluated the contribution of four critical variables to the overall variability. Two lots of each variable were examined in a controlled experiment. The variables tested for ELISA were analyst, plate washer, biotinylated-therapeutic protein, and streptavidin–horseradish peroxidase; and for Biacore were analyst, instrument, chip lot, and conjugation chemistry reagent lots. Equivalence in the mean signal to noise (S/N) or mean relative units (RU) between the two labs was established through statistical evaluation of the assay performance characteristics across multiple assay variables. Concordance between the two labs in the individual sample results was subsequently verified both quantitatively and qualitatively. The long-term maintenance of assay stability was monitored by performance testing of a predefined set of samples which were prepared in sufficient quantities to last several years. The process of method validation for biomarker testing in clinical trials is to analyze the variability of the assay performance. However, different factors contribute to this variability and need to be evaluated when the method is transferred to another site/lab. Lack of understanding the critical variables can potentially result in unexpected problems and delays. The three-step statistical approach of assay transfer provides a robust process for transferring complex biological assays.
Authors and Affiliations
Suzanna Tatarewicz, Michael Moxness, Dohan Weeraratne, Lei Zhou, Michael Hale, Steven J. Swanson, Narendra Chirmule
Keywords
Related Articles
- EP ID EP681487
- DOI 10.1208/s12248-009-9130-3
- Views 91
- Downloads 0
Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway
The online version of this article (doi:10.1208/s12248-016-9901-6) contains supplementary material, which is available to authorized users.
Paradigm Shift in Toxicity Testing and Modeling
The limitations of traditional toxicity testing characterized by high-cost animal models with low-throughput readouts, inconsistent responses, ethical issues, and extrapolability to humans call for alternative strategies...
An Exact Procedure for the Evaluation of Reference-Scaled Average Bioequivalence
The online version of this article (doi:10.1208/s12248-016-9873-6) contains supplementary material, which is available to authorized users.
Lung microdialysis—A powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)
In vivo measurement of concentrations of drugs and endogenous substances at the site of action has become a primary focus of research. In this context the minimal invasive microdialysis (MD) technique has been increasing...
Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective
Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA’s clinical pharmacology review...