January 1, 1970 (Vol. , No. )
Mattias Bylund Product Manager Gyros
Biopharmaceutical development relies heavily on immunoassays to identify, measure, and validate drug candidates from discovery through preclinical and clinical trials and all the way into production. ELISA remains the leading immunoassay method today, enjoying widespread use in many laboratory settings. Nevertheless, the technique is not without its drawbacks. Traditional ELISA assays take a considerable time to complete and the risk of dilution errors and other manual mistakes is always present. This article, the first of two, describes the Gyrolab™ immunoassay technology platform, focusing on its ability to save time during biopharma development and generate higher quality data. The second will examine miniaturization and the transfer of assays between collaborating groups. Both refer to “real-life” case studies.
What Is Gyrolab Technology?
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 where centrifugal force, capillary action and hydrophobic barriers control the parallel processing of up to 112 reactions at nanoliter-scale volumes with short incubation times and minimal matrix effects.
Figure 1 illustrates how this affinity flow-through technology directs the passage and volumes of sample and assay reagents. Integration with fast, powerful software modules designed for 21 CFR Part 11 compliance allows users to quickly analyze their results and use the conclusions to progress their development work further.
Saving Time in Biopharma Development
As the primary objective of the biopharma industry is to make new improved diagnostics and therapeutics available to patients as quickly as possible, time is critical to every aspect of product development. Time saved in R&D, validation and scale-up can significantly contribute to earlier and more conclusive clinical trials, for example.
Biopharma companies that have successfully reduced development times often attribute their success to automation. Automated immunoassay platforms can speed time to completion, both for new assay development and for routine testing. Walk-away automation also frees up staff to do higher-value work while assays are running.
Case Study: Higher Throughput Phase III PK Sample Analysis at Morphotek
The Bioanalytical Development team at Morphotek, the Pennsylvania-based developer and manufacturer of novel classes of biological-based products to treat cancer, inflammation and infectious diseases, faced the task of running a pharmacokinetic (PK) assay on a large backlog of samples to meet the tight deadlines of a Phase III study. They were, however, constrained by the limited throughput of their current validated assay. Switching to Gyrolab xP workstation enabled them to develop a highly automated ligand-binding assay for measuring a humanized monoclonal antibody. Freed from the limitations of hands-on ELISAs, a single company analyst was able to prepare a second set of samples while the first set was running. These were thus ready for automated overnight running as soon as the first set was finished.
Figure 2 illustrates this workflow. The team analyzed 2050 samples per week, generated over 16,000 valid sample results in about six months (with a 95.6% passing rate), and met the deadlines for the study.
Generating Higher Quality Data
Faster product development is not the only reason why laboratories switch from conventional ELISAs to an automated assay platform. They do so because they also acquire higher quality data that enables data-driven decision-making.
A robust immunoassay platform with automated workflows avoids handling errors associated with manual methodologies. The results it yields will thus be more precise and more reproducible.
In addition, a platform with broad dynamic range, such as Gyrolab systems, can lower the minimum required dilution (MRD), further reducing experimental variability caused by dilution error. Note also that a broad dynamic range can be especially valuable in applications requiring the detection of very low concentrations of analyte.
Case Study: More Precise Quantification of Bioprocess Impurities at Pfizer
Host-cell proteins (HCPs) are a major group of impurities for biologic drugs produced in cell culture expression systems. Accurate quantification of HCPs is critical, but also challenging. Today, broad-spectrum ELISAs are commonly used for this task.
In their search for a more precise assay technology, the Analytical Research and Development team in the BioTherapeutics Pharmaceutical Sciences group at Pfizer compared their standard ELISA to several automated immunoassay platforms, including Gyrolab xP. After having evaluated and compared precision, accuracy, linearity and dynamic range, the team concluded that the Gyrolab platform stood out due to its performance characteristics (including precision) and efficiency. It yielded superior quantitative results compared to ELISA with very high (0.96) correlation.
Table 1 demonstrates the increase in data quality obtained by Gyrolab xP compared with standard ELISA. Note also the much faster time-to-result (1.5 hrs vs. 8 to 24 hrs) that the automated workflow offers.
Switching to an Automated Immunoassay Platform
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, including serum, plasma, synovial fluid, tears, urine, whole blood, sputum, vitreous humor, CSF, and cell culture supernatant. Furthermore, users enjoy full flexibility in choosing assay format, e.g. standard sandwich, indirect or bridging (Figure 3). In most cases, the same antibodies currently used in ELISA can be transferred to a Gyrolab assay, thereby ensuring experimental continuity and facilitating regulatory compliance. In addition to having this design freedom, optimized off-the-shelf kits for a range of assays add convenience and boost time saving even further. Finally, the Gyrolab platform is fully scalable from research and discovery phases through preclinical validation to scale-up.
Transferring immunoassays from traditional standard formats such as ELISA onto an automated platform like Gyrolab will save time in assay development and routine assay processing. A robust automation platform will also increase data reproducibility, precision and dynamic range for a wide range of assays, thereby generating greater confidence in the results obtained. The second article will include a typical workflow for transferring an ELISA assay to the Gyrolab platform.