Consistent discussion and improvement upon the standard practices of bioanalytical laboratories is critical to improving the work we do supporting innovative biologics development in the long-term. One of the rapidly advancing areas that is being regularly discussed in the industry is the evolution of ligand-binding assay (LBA) platforms. In this blog, I will summarize best practices and characteristics associated with LBA platforms as well as the features these platforms absolutely need to enable scientists to respond to industry pressures that drive demand for increasingly complex bioanalysis, condensed timelines, and continued output of quality results.
Ideal Characteristics of a Ligand Binding Assay Platform
Analytical performance is critical for an LBA platform to be able to support pharmacokinetics (PK), immunogenicity, biomarker investigation, and potency determination throughout the lifecycle of a therapeutic, from discovery to commercialization. At a minimum, the following characteristics should be considered for new LBA platforms: sensitivity, precision, dynamic range, matrix interference, robustness and ruggedness, and total assay time. In particular, sufficient sensitivity must allow for the detection of the given analyte in a specific application. The recent shift towards the development of more potent therapeutics used at lower doses necessitates a more sensitive platform that can accurately quantify low drug concentrations. Sensitivity is especially impactful when it comes to immunogenicity’s effect on pharmacokinetics and the safety of large molecule drugs. Hand in hand with sensitivity comes precision, and it is also a key consideration for any potential platform. Reproducible data is vital for large molecule studies that often take years to complete, and a high level of precision is needed to achieve and maintain the required level of quality over time. In fact, precision is so critical that LBA platforms used in support of regulated studies should have less than 20% coefficient of variation.
In addition to these somewhat more obvious characteristics, a wide dynamic range is very desirable when it comes to LBA platforms. Because of the wide variety of studies that take place during drug development, broad dosing ranges across the board, and the increased potency of modern therapeutics, a dynamic range exceeding 3 logs may even be needed to ensure appropriate monitoring of anti-drug antibody (ADA) responses. Matrix interference is another consideration that has become more important as drug development has evolved. An LBA platform should have a high tolerance for interference, allowing for the development of more sensitive assays and enhanced detection overall.
Empowering Efficiency with Multiplexing Capabilities
In addition to the other needed characteristics described above, an LBA platform should have multiplexing incorporated. Multiplexing allows for the measurement of multiple analytes from a single sample, which is critical when sample volumes are limited. An LBA multiplex platform should maintain its performance characteristics similar to the respective single assays, regardless of multiplex density. The range of analytes with which we work in a modern bioanalytical lab necessitates a wide dynamic range to allow for extensive multiplexing. Other key considerations include minimal cross-talk; option to limit data collection of assays; ability to collect data in a reasonable time frame; and onboard data reduction software.
An Increased Need for Flexibility and High Throughput
At the same time demand for large molecule drugs increases, project timelines are condensing. Laboratories that deal in ligand binding assays are under pressure to produce high-quality results with fewer resources. A platform that has a high level of flexibility can help expedite projects throughout the project lifecycle. When determining if an LBA platform is flexible enough to meet the requirements of a project it is essential to consider the dynamic range, multiplexing capability, automation compatibility, sample processing time, and volume of sample needed per run. In recent years, automation compatibility has become exponentially more important, as it is possible to test lower sample volumes and increase throughput when a platform can be automated. In some studies, sample volumes can be very limited, so a platform that can be part of an automated process may be necessary.
BioAgilytix’s Suite of Advanced Bioanalytical Platforms
With a focus on bringing on not only the most advanced, but the most useful technologies, BioAgilytix looks for flexible LBA platforms that permit multiplexing and achieve a wide dynamic range, sufficient sensitivity, and a short total assay time in order to meet our sponsors’ complex needs and stringent timelines. In our extensive work in PK, biomarker, and immunogenicity evaluation, we have seen the importance of working with robust LBA platforms that can meet stringent regulatory requirements. Bioanalytical platforms are developing rapidly, like many aspects of the pharma and biotech industries. I am looking forward to discovering how consumer needs and scientific advances will prompt platforms to improve, in an effort to better serve the end user.
Interested in learning about the bioanalytical platforms BioAgilytix employs for research and development ligand binding assays? Visit our platform page and explore our world-class technology suite.