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March 08, 2016

Automating and Miniaturizing Immunoassays: Continuing the Progress to Maximum Productivity

  • The first article in this two-article series (Automating and Miniaturizing Immunoassays: Starting the Switch to Maximum Productivity) describes the Gyrolab™ immunoassay technology platform, focusing on its ability to save time during biopharma development and to generate higher-quality data compared with traditional enzyme-linked immunosorbent assays (ELISAs). This article continues the same theme. It shows (a) how miniaturizing immunoassays can deliver significant savings in sample volumes and (b) how the Gyrolab platform secures smooth assay/method transfer between key entities such as pharma companies, CROs, and CMOs, even those on different continents. As in the first article, "real-life" data is used to support these examples.

  • Gyrolab technology in brief

    Gyrolab is an open technology platform that automates immunoassay workflows by integrating sample addition, washing, and detection in a unique compact disc (CD) format. These CDs contain exact microstructures that control the parallel processing of up to 112 reactions at nanoliter-scale volumes. Integration with fast, powerful software modules designed for 21 CFR Part 11 compliance allows users to analyze results quickly and draw reliable conclusions.

  • Reducing sample size and reagent consumption

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    Miniaturizing immunoassays can deliver tremendous savings in sample volumes, animal use, and reagent consumption. Although reducing assay volumes in manual ELISA immunoassays is possible, it is tedious to carry out and challenging to maintain assay performance. Both issues may ultimately erode anticipated cost savings. In contrast, assay miniaturization on an automated platform not only delivers operational cost savings, it also promotes greater certainty by enabling more experiments and generating more data points from each sample. The study below illustrates one successful example of assay miniaturization on Gyrolab.

    Case Study: Reduced Sample Volume Boosts Rodent Studies at Eli Lilly
    A research group at Eli Lilly wanted to use their anti-drug antibody (ADA) acid dissociation and toxicokinetic assays in rodent studies. However, performing reliable assays on the limited sample volumes available from small animals required significant changes in both productivity and performance. What’s more, their previous attempts to convert these assays to other ELISA formats, such as electrochemiluminescence (ECL) and solid-phase extraction with acid dissociation (SPEAD), had been unsuccessful in achieving the required improvements. Converting to the Gyrolab platform resolved this dilemma. Researchers were able to reduce the sample volume (per duplicate) from 25 µL to 4 µL and shorten the time-to-result from 23 hours to just 4 hours. A notable improvement in drug tolerance was also observed. Table 1 summarizes these results.

  • Increasing assay transfer efficiency between collaborating groups

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    The smooth transfer of assays from biotherapeutic development groups to entities such as CROs and CMOs for validation, clinical sample testing, and other downstream processes are also areas where significant gains can be made. Using a shared automated technology platform such as Gyrolab greatly facilitates data analysis and interpretation among collaborating groups. The case study summarized below demonstrates the successful transfer and cross-validation of a Gyrolab pharmacokinetic (PK) assay in three countries to meet the needs of a clinical trial.

    Case Study: Transfer and Cross-Validation of a Gyrolab Platform Assay across Three Different Countries on Two Continents
    The Gyrolab platform was chosen for its ability to deliver fast turnaround using small sample volumes. The PK assay was first validated at the drug discovery and development company Novimmune in Switzerland before being transferred to a CRO in the U.K. for validation. This was followed by a transfer to a second CRO in the U.S. for further validation. Finally, the assay was cross-validated at all three sites. Figure 1 shows an overview of this process.

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    The assay delivered a working range of 62.5–8000 ng/mL and passed the criteria for the initial validation, including intra- and interaccuracy and precision (±20% or less relative error [RE] and coefficient of variation [CV] or 25% RE and CV for lower limit of quantification [LLOQ]/upper limit of quantification [ULOQ]), matrix effects, dilutional linearity (up to 1 in 2000), lack of hook effect, short-term stability at room temperature after five freeze–thaw cycles, and long-term stability at –20 and –80°C.

    Cross-validation at the three sites to assess ruggedness involved blinded tests on 30 samples at the CROs (Figure 2). The relative percentage difference between the reference result (Novimmune) and observed result (CRO) was better than ±25% for 87% of the samples, which surpassed the set acceptance criteria. This demonstrates the equivalence of the assay across the three sites, and therefore this assay could be relied upon to deliver the data needed in the multisite project.

  • Switching to an automated immunoassay platform

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    Switching from an ELISA format to Gyrolab immunoassay technology should not present any major difficulties. Assays that run on Gyrolab can be developed in a variety of matrices, and users enjoy full flexibility in choosing assay format. In most cases, the same antibodies currently used in ELISA can be transferred to a Gyrolab assay. Furthermore, the Gyrolab platform is fully scalable from research and discovery phases through preclinical validation to scale up. Figure 3 outlines a typical five-step workflow for transferring an ELISA assay to the Gyrolab platform.

    Conclusions

    Transferring immunoassays from traditional standard formats such as ELISA onto an automated platform like Gyrolab offers biopharma developers several tangible benefits. Assay miniaturization saves operating costs and improves other aspects of assay performance while the built-in robustness facilitates validating and transferring assays between laboratories, a common task today when drug development often involves multisite clinical trials, frequently on different continents.

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