Ligand Binding Assays in the 21st Century Laboratory: Platforms

The 21st Century Bioanalytical Laboratory Platforms initiative in the BIOTEC section of the American Association of Pharmaceutical Scientists (AAPS) began with a pre-conference workshop held in Seattle, WA in June of 2009. This workshop brought together members of the pharmaceutical and biotechnology industries, with instrument and reagent manufacturers to discuss the current and potential future state of the bioanalytical laboratories supporting biologics development. At the conclusion of the workshop, four sub-teams were formed to further develop the ideas and concepts raised during the 2-day workshop. The sub-teams are reagents, automation, e-solutions, and platforms. This paper discusses the critical attributes of a research and development ligand binding assay (LBA) platform and the desired characteristics new platforms should strive to offer in the future. This paper is not intended to be a review and comparison of the current platforms on the market, as this has been done and published elsewhere (1–9). The platforms team consists of a balanced cross-section of the industry with representatives from pharmaceutical, biotechnology, contract research organizations, and instrument manufacturers. The Platforms team have collaborated to discuss and arrive at a consensus regarding the most useful characteristics of a bioanalytical platform for biologics. We present here the results of these discussions. A platform is the technology employed in an analytical method to transduce a biochemical event into a measureable output or signal. This signal allows the bioanalytical scientist to accurately and reproducibly make measurements to analyze different aspects of a specific biologic target (therapeutic, biomarker, and anti-drug antibody) such as its pharmacokinetics, immunogenicity, potency, or effect of biomarkers. An instrument is the tool utilized minimally to measure a platform’s output and convert the resultant signal into interpretable information the analytical scientist can use but can incorporate other aspects such as liquid handling. Many platforms employ optical signals including the absorbance of light through a medium (10) or the emission of fluorescence (10) or luminescence (11). A variety of light detectors are used to measure these optical signals including photo diodes, charge-coupled device cameras, and photo-multiplier tubes (Table I). Sections in this paper provide details on the desirable analytical characteristics, multiplexing, platform flexibility and throughput, desirable instrument characteristics, and finally, life cycle management of the ideal LBA platform. Table I Commonly Used Platforms The analytical characteristics of today’s ligand binding assays are primarily influenced by three major factors—the quality of the reagents, assay format, and the choice of the analytical platform. This paper describes only those aspects derived from the analytical platform.