Singlicate Gyrolab immunoassays prove their worth (again)
In a previous post, ‘How to get it right first time’, we looked at the reliability and reproducibility of Gyrolab™ assays that lead to the idea of running singlicates instead of duplicates (Clark et al, 2016). This publication inspired Hao Jiang and colleagues in a group based at Bristol-Myers Squibb in Princeton, USA to apply Gyrolab technology to run assays of their monoclonal antibody in singlicate in a clinical study. They were encouraged by the results.
The drive to achieve regulatory approval of protein-based drugs quickly and efficiently demands methods that can deliver reliable data to support studies in pharmacokinetics, toxicokinetics, pharmacodynamics, biomarker analysis, and immunogenicity. This need has powered the development of a wide and somewhat perplexing range of ligand binding assays (LBAs) and technology platforms designed to function in a regulated environment, from non-clinical studies to post approval. Added to that, developing an assay that is ready for validation can be a real challenge. If you need guidance in this area then you would do well to read ‘Ligand Binding Assays in the Regulated Bioanalytical Laboratory’, a book chapter authored by Johanna Mora
A number of serious eye diseases, such as neovascular age-related macular degeneration (AMD) and diabetic macular edema, involve increase in the leakage of blood vessels in the eye. This is caused by vascular endothelial growth factor (VEGF) and while such diseases can be treated with protein drugs that neutralize VEGF, the drugs must be administered frequently. A research group has developed an elegant approach that significantly extends the half-life of the drugs. This exciting work involved handling a challenge that is common to much of eye research – running immunoassays on precious samples in difficult matrices.
Bioanalytical laboratories often need to quickly develop robust immunoassays to support studies with tight timelines. Immunoassay performance is governed by many factors, such as reagent concentrations and sample dilution, and the classic experimental approach to improving assay performance involves changing one factor at a time. This approach is time consuming, misses important interactions between factors, and seldom leads to an optimal assay. There is an alternative, very powerful approach that has been used in many industries and applications to optimize processes – Design of Experiments (DOE). DOE has been successfully applied to immunoassay development by a number of research groups, including those using Gyrolab technology.
Immunoassays are only as good as the reagents they build on. Following up on the post 
Anti-Drug Antibodies (ADA) can decrease drug half-life, reduce drug efficacy and even cause serious adverse reactions. Measuring ADA is therefore a key safety concern, but the immunoassays used to do this are complicated by the presence of drug and target in samples, which may severely reduce assay selectivity. This demands immunogenicity assays that are a balancing act between sufficient sensitivity, drug tolerance, and resistance to target interference.
It’s the Achilles heel of the ligand-binding assay (LBA). That is how matrix effects are described by one author in the Bioanalysis Special Focus Issue, ’Matrix effects in LBAs’. This issue includes valuable editorials and a diverse collection of articles by experts concerning matrix interference, how it affects selectivity, and how it can be reduced. Minimizing interference has many benefits for LBAs, including lower sample dilution, higher sensitivity, and increased robustness.
