Future Immunoassay Approaches in Modern Bioprocess Development

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Modern bioprocess development requires accurate, high throughput analytical methods to match scaled-down, high-throughput screening, the application of DoE, and science-based decision making consistent with QbD. Gyrolab™ systems and Gyros’ immunoassay kits constitute a proven platform that supports these needs today and has the capability to meet future challenges.

The assay principle uses high-capacity, flow-through affinity columns embedded within a CD. Centrifugal force, capillary action and hydrophobic barriers are exploited during parallel processing of up to 112 samples on each CD. A biotinylated anti-analyte antibody is bound to streptavidin-coated particles in the affinity micro-columns within the CD. The samples are transferred to the CD, followed by another anti-analyte antibody, this time labelled with a fluorophore. The detector then records laser-induced fluorescence from each micro-column. Samples are quantitated using a standard curve and results are evaluated with Gyrolab Evaluator software or exported. Automation, parallel processing, hands-free operation and no incubation combine to give more results in shorter time than conventional ELISAs. The platform allows development of assays with your own reagents, or adaptation of existing ELISAs, as well as the use of off-the-shelf kits from Gyros. Advantages of the CD flow-through column format include large dynamic range, short analysis times, and low matrix interference. Assays employing Gyrolab systems consume low volumes of reagents and need as little as 4 μL of each sample. Gyrolab xPlore is a single-CD instrument for automated immunoassays in laboratories of every size. For higher throughput needs, Gyrolab xP workstation offers automated processing of up to five CD’s. Running round the clock, Gyrolab xP workstation can deliver roughly 1000 data points per day.

The great interest in improving analytical methods to cope with modern bioprocess development is reflected in published literature and presentations made at meetings. We summarize reports using Gyrolab technology made by scientists from several biopharmaceutical companies.

At Shire, work showed that Gyrolab technology can simplify assay development, streamlining antibody pair analysis and method qualification, as well as providing assays with broad dynamic range, high precision and good sensitivity. At MedImmune, in a GMP environment, dramatic improvements in assay set up times, productivity and success rates were achieved by applying Gyrolab systems. Scientists from Merck studied dynamic range, limit of quantification, dilution linearity, spike recovery, and inter and intra-assay variation for HCP analysis, comparing Gyrolab systems with manual ELISA and robot-automated ELISA. Higher throughput and improved performance allowed Merck scientists to rapidly screen product titers in hundreds of clones and to study HCP removal during purification method development using a DoE approach.

Gyrolab technology reduces errors associated with hands-on operations and increases analytical lab productivity. Kits are available for determination of human IgG titers, CHO cell HCPs and Protein A impurities, offering a fast, effective and convenient start when working with therapeutic proteins of mammalian cell origin, in particular human monoclonal antibodies derived from CHO cells. (470)